Cancer

PALLADIUM (II) COMPLEXES CONTAINING N-HETEROCYCLIC CARBENE LIGAND, SYNTHESIS, AND APPLICATIONS IN CANCER TREATMENT (Fri, 16 Feb 2018)
Palladium (II) N-heterocyclic carbene (NHC) complexes which are stable in the presence of biological thiols. A representative complex, [Pd (C^N^N) (N, N'-nBu 2NHC) ] (CF 3SO 3) (Pd1d, HC^N^N = 6-phenyl-2, 2'-bipyridine, N, N'-nBu 2NHC=N, N'-di-n-butylimidazolium), displays potent killing activity toward cancer cell lines but is less cytotoxic toward normal human fibroblast cell lines.
>> Read More

CHIMERIC ANTIGEN RECEPTORS TARGETING BCMA AND METHODS OF USE THEREOF (Fri, 16 Feb 2018)
Provided are single-domain antibodies targeting BCMA, and chimeric antigen receptors (such as monovalent CAR, and multivalent CAR including bi-epitope CAR) comprising one or more anti-BCMA single-domain antibodies. Further provided are engineered immune effector cells (such as T cells) comprising the chimeric antigen receptors. Pharmaceutical compositions, kits and methods of treating cancer are also provided.
>> Read More

NEW ATR INHIBITORS FOR THE USE IN CANCER THERAPY (Fri, 16 Feb 2018)
This invention relates to pyrazine compounds having a sulfilimine or sulfoximine groups and to the use of said compounds for treating cancer. Furthermore the invention relates to combination treatment using said compounds. Finally, the present invention also relates to pharmaceutically acceptable composition comprising the compounds of this invention, and processes for preparing the compounds of this invention.
>> Read More

THERAPEUTIC AND DIAGNOSTIC METHODS FOR CANCER (Fri, 16 Feb 2018)
The present invention provides therapeutic and diagnostic methods and compositions for cancer and for enhancing immune function in an individual having cancer. The invention provides methods of treatment, methods for determining whether an individual suffering from a cancer is responding to treatment comprising a PD-1 axis binding antagonist, predicting responsiveness of an individual suffering from a cancer to treatment comprising a PD-1 axis binding antagonist, and methods of selecting a therapy for an individual suffering from cancer.
>> Read More

PROCESS FOR THE PREPARATION OF 3ß-HYDROXY-17-(1H-BENZIMIDAZOL-1-YL)ANDROSTA-5,16-DIENE (Fri, 16 Feb 2018)
A process for the synthesis of β-hydroxy 3-17-(1H-benzimidazol-1-yl)androsta-5,16-diene is described, a compound also known as Galeterone and used in the treatment of prostate cancer, having the formula (6).
>> Read More

FURANOCHALCONES AS INHIBITORS OF CYP1A1, CYP1A2 AND CYP1B1 FOR CANCER CHEMOPREVENTION (Fri, 16 Feb 2018)
The present invention relates to the furanochalcone class of compounds of general formula A. The present invention particularly relates to the synthesis of furanochalcones and their CYP1A1, CYP1A2 and CYP1B1 inhibitory activity. In addition, the invention relates to the prevention or treatment of cancer caused by polyaromatic hydrocarbons (PAHs), 4-nitroquinoline-1-oxide, and N-nitroso-N- methylurea, heterocyclic amines, estrogen and 17β-estradiol, resulting from the inhibition of CYP1A1, CYP1A2 and CYP1B1 enzymes.
>> Read More

HETEROCYCLIC COMPOUNDS WITH AN ROR(GAMMA)T MODULATING ACTIVITY (Fri, 16 Feb 2018)
The present invention relates to a compound that may have an ROR(gamma)t modulating activity and can thus be useful in the treatment of cancer.
>> Read More

METHODS AND COMPOSITIONS FOR NEAR INFRARED FLUORESCENT NANODOTS WITH AGGREGATION-INDUCED EMISSION CHARACTERISTICS (Fri, 16 Feb 2018)
Disclosed herein is a donor-acceptor-donor (D-A-D) compound of formula I, where in the acceptors are mono-substituted tetraphenylethylene moieties. Also disclosed herein are fluorescent nanodots that comprise the compound of formula (I) and uses of said compound or nanodots in in vivo imaging or detecting of cancer cells in a subject.
>> Read More

DRUG CONJUGATES WITH SELF-STABILIZING LINKERS HAVING IMPROVED PHYSIOCHEMICAL PROPERTIES (Fri, 16 Feb 2018)
Compounds and compositions are disclosed in which a Drug Unit is linked to a targeting Ligand Unit through a self-stabilizing Linker Unit from which a drug compound or active drug moiety is released at the targeted site of action. Methods for treating diseases characterized by the targeted abnormal cells, such as cancer or an autoimmune disease using the compounds and compositions of the invention are also disclosed.
>> Read More

N-(4-HYDROXY-4-METHYL-CYCLOHEXYL)-4-PHENYL-BENZENESULFONAMIDES AND N-(4- HYDROXY-4-METHYL-CYCLOHEXYL)-4-(2-PYRIDYL)BENZENESULFONAMIDES AND THEIR THERAPEUTIC USE (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain substituted N-(4-hydroxy-4-methyl-cyclohexyl)-4-phenyl-benzenesulfonamide and N-(4-hydroxy-4-methyl-cyclohexyl)-4-(2-pyridyl)benzenesulfonamide compounds (collectively referred to herein as HMC compounds) that are useful, for example, in the treatment of disorders (e.g., diseases) including, inflammation and/or joint destruction and/or bone loss; disorders mediated by excessive and/or inappropriate and/or prolonged activation of the immune system; inflammatory and autoimmune disorders, for example, rheumatoid arthritis; psoriasis; psoriatic arthritis; chronic obstructive pulmonary disease (COPD); asthma; atherosclerosis; inflammatory bowel disease; ankylosing spondylitis; multiple sclerosis; systemic lupus erythematosus; Sjogren's syndrome; a disorder associated with bone loss, such as bone loss associated with excessive osteoclast activity in rheumatoid arthritis, osteoporosis, cancer-associated bone disease, or Paget's disease; cancer, such as a haematological malignancy, such as multiple myeloma, leukemia, or lymphoma, or a solid tumour cancer, such as bladder cancer, breast cancer (female and/or male), colon cancer, renal cell carcinoma, kidney cancer, lung cancer, pancreatic cancer, gastric cancer, prostate cancer, brain cancer, skin cancer, thyroid cancer, basal cell ameloblastoma, or melanoma; a disorder associated with fibrosis, such as systemic sclerosis or scleroderma; or a rare vasculitide, such as Behçet's disease. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, for example, in therapy.</p>
>> Read More

STRUCTURED VIRAL PEPTIDE COMPOSITIONS AND METHODS OF USE (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The invention provides structurally constrained viral peptides for use as therapeutic and vaccination agents, and for the production of antibodies for use in a number of applications including as therapeutic agents. The invention further provides methods and kits for use of the structurally constrained peptides and antibodies of the instant invention. The invention is based, at least in part, on the result provided herein demonstrating the viral hydrocarbon stapled helical peptides display excellent proteolytic, acid, and thermal stability, restore the native helical structure of the peptide, are highly effective in interfering with the viral fusogenic process, and possess superior pharmacokinetic properties compared to the corresponding unmodified peptides.</p>
>> Read More

Molecular Antigen Array (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The present invention is related to the fields of molecular biology, virology, immunology and medicine. The invention provides a composition comprising an ordered and repetitive antigen or antigenic determinant array. The invention also provides a process for producing an antigen or antigenic determinant in an ordered and repetitive array. The ordered and repetitive antigen or antigenic determinant is useful in the production of vaccines for the treatment of infectious diseases, the treatment of allergies and as a pharmaccine to prevent or cure cancer and to efficiently induce self-specific immune responses, in particular antibody responses.</p>
>> Read More

ANTIBODIES AGAINST THE MUC1-C/EXTRACELLULAR DOMAIN (MUC1-C/ECD) (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The present disclosure is directed to antibodies binding to MUC1-C/extracellular domain (MUC1-C/ECD) and methods of using such antibodies to treat cancers that express the MUC1 antigen.</p>
>> Read More

SPECIFICALLY meso-SUBSTITUTED PORPHYRINS AND CHLORINS FOR PHOTODYNAMIC THERAPY (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">Biologically active compounds that can be used as photosensitizers for diagnostic and therapeutic applications, particularly for PDT of cancer, infections and other hyperproliferative diseases, fluorescence diagnosis and PDT treatment of a non-tumorous indication such as arthritis, inflammatory diseases, viral or bacterial infections, dermatological, opthamological or urological disorders are provided as well as providing methods to obtain them in pharmaceutical quality. One embodiment consists of a method to synthesize a porphyrin with a defined arrangement of meso-substituents and then converting this porphyrin system to a chlorin system by dihydroxylation or reduction, and if more than one isomer is formed separate them by chromatography either on normal or reversed phase silica. In another embodiment the substituents on the porphyrin are selected to direct the reduction or dihydroxylation to the chlorin so that a certain isomer is selectively formed. Another embodiment is to provide amphiphilic compounds with a higher membrane affinity and increased PDT-efficacy. In other embodiments the nucleophilic substitution on pentafluorophenyl-substituted tetrapyrroles is used to obtain compounds with a high PDT-efficacy. In another embodiment substituents are identified that via their steric and/or electronic influence direct the dihydroxylation or reduction with diimine so that one isomer is favored. Another embodiment consists of formulating the desired tetrapyrrole photosensitizer into a pharmaceutical formulation to be injected into the body avoiding undesirable effects like solubility problems or delayed pharmacokinetics of the tetrapyrrole systems.</p>
>> Read More

NOVEL C-17-HETEROARYL STEROIDAL CYP17 INHIBITORS/ANTIANDROGENS, IN VITRO BIOLOGICAL ACTIVITIES, PHARMACOKINETICS AND ANTITUMOR ACTIVITY (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">Described are steroidal C-17 benzoazoles, pyrimidinoazoles (azabenzoazoles) and diazines. Methods for their synthesis are also described, which include methods having a step of nucleophilic vinylic “addition-elimination” substitution reaction of 3β-acetoxy-17-chloro-16-formylandrosta-5,16-diene or analogs thereof and benzoazole or pyrimidinoazole nucleophiles and methods having a palladium catalyzed cross-coupling reaction of 17-iodoandrosta-5,16-dien-3β-ol or analogs thereof with tributylstannyl diazines. The compounds are potent inhibitors of human CYP17 enzyme as well as potent antagonists of both wild type and mutant androgen receptors (AR). The compounds are useful for the treatment of human prostate cancer.</p>
>> Read More

HETEROARYLENE-BRIDGED BENZODIAZEPINE DIMERS, CONJUGATES THEREOF, AND METHODS OF MAKING AND USING (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">Benzodiazepine dimers having a structure represented by</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.42mm" wi="75.27mm" file="US20180037581A1-20180208-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein X comprises a heteroaromatic moiety and is as further defined in the application; R<sup>1 </sup>is</p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="70.53mm" wi="69.85mm" file="US20180037581A1-20180208-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005" num="0000">and the other variables in formulae (I), (Ia), and (Ib) are as defined in the application. Such dimers are useful as anti-cancer agents, especially when used in an antibody-drug conjugate (ADC).</p>
>> Read More

PURINONE COMPOUNDS AS KINASE INHIBITORS (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. In addition, reversible inhibitors of Btk are also described. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.</p>
>> Read More

Polymer/Copper Combination for Targeted Cancer Therapy (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">Polymer/copper combinations that can selectively target and kill cancer cells are described. Materials can include the reaction product of a biocompatible hydrophilic polymer and pyridine-2-thiol containing monomer. The copolymer reaction product can include pyridine-2-thiol side groups pendant to the backbone via a disulfide linkage. The hydrophilic component can form the polymer backbone and/or can form hydrophilic pendant groups off of the backbone. Copper ions can be associated with the copolymer.</p>
>> Read More

ANTIBODY DRUG CONJUGATES (ADC) THAT BIND TO FLT3 PROTEINS (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">Antibody drug conjugates (ADC's) that bind to FLT3 protein and variants thereof are described herein. FLT3 exhibits a distinct and limited expression pattern in normal adult tissue(s), and is aberrantly expressed in the cancers listed in Table I. Consequently, the ADC's of the invention provide a therapeutic composition for the treatment of cancer.</p>
>> Read More

RILUZOLE PRODRUGS AND THEIR USE (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">Pharmaceutical compositions of the invention include substituted riluzole prodrugs useful for the treatment of cancers including melanoma, breast cancer, brain cancer, and prostate cancer through the release of riluzole. Prodrugs of riluzole have enhanced stability to hepatic metabolism and are delivered into systemic circulation by oral administration, and then cleaved to release riluzole in the plasma via either an enzymatic or general biophysical release process.</p>
>> Read More

9H-PYRIMIDO [4,5-B] INDOLES AS BET BROMODOMAIN INHIBITORS (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The present disclosure provides substituted 9H-pyrimido [4,5-b] indoles and 5H-pyrido [4,3-b] indoles and related analogs represented by Formula I and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R<sup>1a</sup>, W, B<sup>1</sup>, B<sup>2</sup>, G, X<sup>1</sup>, Y<sup>1</sup>, Y<sup>2</sup>, and Y<sup>3 </sup>are as defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a condition or disorder responsive to inhibition of BET bromodomains such as cancer. The present disclosure is also directed to the use of compound of Formula I as synthetic intermediates.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.42mm" wi="50.72mm" file="US20180036294A1-20180208-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

DERIVATIVES OF 2-AMINOPYRIDINE AS ADENOSINE A2B RECEPTOR ANTAGONISTS AND LIGANDS OF THE MELATONIN MT3 RECEPTORS (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The present invention relates to novel pyridine derivatives of formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="16.51mm" wi="51.90mm" file="US20180037569A1-20180208-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">as A<sub>2B </sub>adenosine receptor antagonists and ligands of MT<sub>3 </sub>melatonin receptor, to processes for their preparation, to pharmaceutical compositions comprising said compounds and to the use of said for manufacturing a medicament for the treatment of pathological conditions or diseases that can improve by antagonizing the adenosine A<sub>2B </sub>receptor and by inhibition of MT<sub>3 </sub>melatonin receptor, such as respiratory disease, metabolic disorders, neurological disorders and cancer.</p>
>> Read More

SUBSTITUTED PYRIMIDINE COMPOUNDS AS PHOSPHATIDYLINOSITOL 3-KINASE DELTA INHIBITOR AND USE THEREOF (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The present invention belongs to the field of medicinal chemistry, and relates to substituted pyrimidine compounds as phosphatidylinositol 3-kinase (PI3K) δ inhibitor and a use thereof. In particular, the present invention provides a compound as shown by formula I or an isomer, pharmaceutically acceptable salt, solvate or prodrug thereof, the preparation methods of same and pharmaceutical compositions containing these compounds and a use of these compounds or compositions for treating cancer, hyperblastosis diseases or inflammatory diseases. The compounds of the present invention have a good inhibiting activity on PI3Kδ and have a high selectivity. It is hoped that these will be therapeutic agents for cancer, hyperblastosis diseases or inflammatory diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.03mm" wi="66.46mm" file="US20180037576A1-20180208-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

USE OF INHIBITORS OF BRUTON'S TYROSINE KINASE (BTK) (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">Disclosed herein are methods for treating a cancer comprising: a. administering a Btk inhibitor to a subject sufficient to result in an increase or appearance in the blood of a subpopulation of lymphocytes defined by immunophenotyping; b. determining the expression profile of one or more biomarkers from one or more subpopulation of lymphocytes; and c. administering a second agent based on the determined expression profile.</p>
>> Read More

METHODS OF TREATING CANCER WITH A PSMA LIGAND-TUBULYSIN COMPOUND (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The invention described herein pertains to drug delivery conjugates for targeted therapy. The invention described herein relates to methods of treating PSMA expressing cancers with a PSMA ligand-tubulysin compound. The invention described herein also relates to methods of treating PSMA-expressing cancers with a PSMA ligand-tubulysin compound in patients where stable disease results after treatment with the PSMA ligand-tubulysin compound.</p>
>> Read More

Malate salt of N-(4-phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide.</p>
>> Read More

PRODRUGS RILUZOLE AND THEIR METHOD OF USE (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">Pharmaceutical compositions of the invention include substituted riluzole prodrugs useful for the treatment of cancers including melanoma, breast cancer, brain cancer, and prostate cancer through the release of riluzole. Prodrugs of riluzole have enhanced stability to hepatic metabolism and are delivered into systemic circulation by oral administration, and then cleaved to release riluzole in the plasma via either an enzymatic or general biophysical release process.</p>
>> Read More

THERAPEUTIC AND DIAGNOSTIC METHODS FOR CANCER (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The present invention provides therapeutic and diagnostic methods and compositions for cancer, for example, bladder cancer. The invention provides methods of treating bladder cancer, methods of determining whether a patient suffering from bladder cancer is likely to respond to treatment comprising a PD-L1 axis binding antagonist, methods of predicting responsiveness of a patient suffering from bladder cancer to treatment comprising a PD-L1 axis binding antagonist, and methods of selecting a therapy for a patient suffering from bladder cancer, based on expression levels of a biomarker of the invention (e.g., PD-L1 expression levels in tumor-infiltrating immune cells in a tumor sample obtained from the patient) and/or based on the determination of a tumor sample subtype.</p>
>> Read More

PROCESS FOR PREPARING SUBSTITUTED QUINOLIN-4-OL COMPOUNDS (Fri, 09 Feb 2018)
The invention relates to a process for preparing substituted quinolin-4-ol compounds useful for preparing protein tyrosine kinase (PTK) inhibitors which are useful in treating cancer.
>> Read More

CRISSCROSS COOPERATIVE SELF-ASSEMBLY (Fri, 09 Feb 2018)
Provided herein, in some embodiments, are methods, compositions and kits for controlling nucleation and assembly of molecular nanostructures, microstructures and macrostructures.
>> Read More

CD40-BINDING AGENTS AND USES THEREOF (Fri, 09 Feb 2018)
Polypeptides and agents that bind human CD40 are disclosed. The polypeptides or agents may include fusion polypeptides, particularly polypeptides comprising the extracellular domain of CD40L or a fragment thereof. The agents may include bispecific and multispecific agents. Also disclosed are methods of using the polypeptides or agents for inducing and/or enhancing the immune response, as well as methods for the treatment of diseases such as cancer.
>> Read More

2,7-DIAZASPIRO[4.4]NONANES (Fri, 09 Feb 2018)
The present invention covers 2,7-diazaspiro[4.4]nonane compounds of general formula (I): in which n, X, R2, R3, R4, R5, R6a and R6b are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer or diabetes, as a sole agent or in combination with other active ingredients.
>> Read More

PIPERIDINE DERIVATIVES FOR USE IN THE TREATMENT OF PANCREATIC CANCER (Fri, 09 Feb 2018)
The present invention relates to novel piperidine derivatives having better cell growth inhibitory activities toward cancer cell cultures and, more particularly, PANC-1 cancer cell cultures than FK866. Accordingly, the present invention relates to compounds of formula (I), wherein Ar1 is aryl or heteroaryl, which are optionally substituted by one, two or three substituents selected from lower alkyl; lower alkoxy; formyl; hydroxyl; lower alkyl substituted by lower alkoxy or hydroxyl; A is CnH2n, CnH2n-2 or CnH2n-4, wherein n=4,5,6,7; B is =N-CN, oxo (=0), thio (=S); D is NH, -CH=CH-; Ar2 is aryl or heteroaryl which are optionally substituted by one, two or three halogen substituents; wherein, if B is oxo (=0), Ar1 and Ar2 are not simultaneously phenyl and pyridine-3-yl; B and D are not simultaneously =N-CN and -CH=CH-, or a pharmaceutically acceptable salt, a racemic mixture or its corresponding enantiomers and/or optical isomers. The compounds of formula (I) and their pharmaceutically usable addition salts possess valuable pharmacological properties. Specifically, it has been found that the compounds of the present invention, alone or in combination with other therapeutic active compounds, have an activity as chemotherapeutic agents against cancer and, more particularly, pancreatic cancers.
>> Read More

SYNTHESIS OF NEW PHOSPHORUS DENDRIMERS AND USE THEREOF (Fri, 09 Feb 2018)
An object of this invention is synthesis of cationic phosphorus dendrimers of 3rd and 4th generation, possessing on the periphery the amino- and terminal functional P(S)C12 groups grafted with l-(2-aminoethyl)-piperidine and having the following structures where AE2G3H+ stands for cationic phosphorus dendrimer of generation 3, AE2G4H+ for cationic phosphorus dendrimer of generation 4. The invention covers also use of the dendrimers as delivery systems of the genetic material to cancer cells.
>> Read More

N-(PHENYLSULFONYL)BENZAMIDES AND RELATED COMPOUNDS AS BCL-2 INHIBITORS (Fri, 09 Feb 2018)
The present disclosure provides compounds having Formula I-A: and the pharmaceutically acceptable salts and solvates thereof, wherein A, X1 , X2, X3 R1a, R1b E, and = are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I-A for use to treat a disease, disorder, or condition responsive to Bc1-2 protein inhibition such as cancer.
>> Read More

ANTIBODY-RECRUITING MOLECULES FOR THE TREATMENT OF CANCER (Fri, 09 Feb 2018)
The present invention relates to- chimeric (including Afunctional) compounds, compositions comprising those compounds and methods of treating cancer in a patient or subject, especially including metastatic and other cancers where cancer ceils exhibit overexpression (heightened expression) of cell surface TOokinase-type plasminogen activator receptor (urokinase receptor) compared to normal (non-cancerous) cells. The compounds bind to the urokinase-type plasminogen acti vator receptor (uPAR) on the surface of a cancer cell, including a metastatic cancer cell, and consequently recruit native antibodies of the patient or subject where the antibodies can Selectively degrade and/or deactivate targeted cancer ceils through antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) against a. large number and variety of cancers, thus providing cancer cell death and an inhibition of growth, elaboration and/or metastasis of the cancer, including remission and cure of the patient's cancer.
>> Read More

MONOCYCLIC COMPOUND (Thu, 08 Feb 2018)
The present invention relates to a compound which may be useful as an agent for the prophylaxis or treatment of cancer, hepatitis, hepatic fibrosis, fatty liver and the like.
>> Read More

PIPERIDINE DERIVATIVES FOR USE IN THE TREATMENT OF PANCREATIC CANCER (Thu, 08 Feb 2018)
The present invention relates to novel piperidine derivatives having better cell growth inhibitory activities toward PANC-1 cancer cell cultures than FK866. Accordingly, the present invention relates to compounds of formula I, wherein Ar 1 is aryl or heteroaryl, which are optionally substituted by one, two or three substituents selected from lower alkyl; lower alkoxy; formyl; hydroxyl; lower alkyl substituted by lower alkoxy or hydroxyl; A is C n H 2n , C n H 2n-2 or C n H 2n-4 , wherein n=4,5,6,7; B is =N-CN, oxo (=O), thio (=S); D is NH, -CH=CH-; Ar 2 is aryl or heteroaryl which are optionally substituted by one, two or three halogen substituents; wherein, if B is oxo (=O), Ar 1 and Ar 2 are not simultaneously phenyl and pyridine-3-yl; B and D are not simultaneously =N-CN and -CH=CH-, or a pharmaceutically acceptable salt, a racemic mixture or its corresponding enantiomers and/or optical isomers. The compounds of formula I and their pharmaceutically usable addition salts possess valuable pharmacological properties. Specifically, it has been found that the compounds of the present invention, alone or in combination with other therapeutic active compounds, have an activity as chemotherapeutic agents against pancreatic cancers.
>> Read More

Pharmaceutically acceptable salts of B-guanidinopropionic acid with improved properties and uses thereof (Wed, 07 Feb 2018)
<p id="p-0001" num="0000">The present invention relates to new pharmaceutical salts of β-GPA which exhibit improved physical properties. In particular, the invention relates to salts of β-GPA with improved flow properties (e.g., improved Carr's index and/or Hausner ratio) such as fumarate salts, succinate salts, and oxalate salts. The invention also relates to pharmaceutical compositions including a pharmaceutically effective amount of one or more salts of β-GPA, as well as methods of treating cancer including administration of a formulation including a β-GPA salt of the invention to a subject in need thereof.</p>
>> Read More

THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">Provided are crystalline forms of 2-Methyl-1-[(4-[6-(trifluoromethyl) pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol mesylate useful for treating cancer and methods of treating cancer, comprising administering to a subject in need thereof said compound.</p>
>> Read More

USE OF STING AGONIST AS CANCER TREATMENT (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">Methods and compositions for treating cancer by intratumorally administering a stimulator of interferon genes (STING) agonist are disclosed herein.</p>
>> Read More

MODIFICATIONS OF THERAPEUTIC AGENTS FOR ENHANCED DELIVERY TO TARGET SITES (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">Compositions of a modulator of cell metabolism, typically targeting cellular glycolysis, preferably with a targeting moiety, attached directly or indirectly to the inhibitor, or to a nanoparticle or other delivery vehicle thereof, and methods of use for treating cancer, proliferative disorders, neurodegenerative diseases, autoimmune disorders, or inflammatory diseases are provided. Pharmaceutical compositions including the targeted modulator and a pharmaceutically acceptable carrier are also provided. The pharmaceutical compositions can be administered to a subject in need thereof in an effective amount to reduce one or symptoms of the cancer, proliferative disorders, neurodegenerative diseases, autoimmune disorders, or inflammatory diseases alone or prior to or in conjunction with a further therapy such as radiotherapy.</p>
>> Read More

PHARMACEUTICALLY ACTIVE COMPOUNDS (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The invention is directed to compounds of general formula (I), and pharmaceutical compositions containing such compounds. The compounds and compositions have valuable pharmaceutical properties. In particular, they may be used for the treatment of cancer. Novel intermediates and novel methods of preparation are also disclosed.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.24mm" wi="64.35mm" file="US20180029985A1-20180201-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

NOVEL GROUP OF STAT3 PATHWAY INHIBITORS AND CANCER STEM CELL PATHWAY INHIBITORS (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The present invention relates to the use of a novel class of cancer stem cell pathway (CSCP) inhibitors; to methods of using such compounds to treat refractory, recurrent, or metastatic cancers; to methods of selective killing cancer cells by using such compounds with specific administration regimen; to methods of targeting cancer stem cells by inhibiting Stat3 pathway; to methods of using novel compounds in the treatment of conditions or disorders in a mammal related to aberrant Stat3 pathway activity; and to processes for preparing such compounds and intermediates thereof, and to the pharmaceutical compositions of relevant compounds, and to the specific methods of administration of these compounds.</p>
>> Read More

ANTI-PD-1 ANTIBODIES (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The present invention relates to anti-PD-1 antibodies, as well as use of these antibodies in the treatment of diseases such as cancer and infectious disease. These antibodies have CDRs as provided in the enclosed sequences. Also part of the invention are nucleic acids encoding these antibodies, expression vectors comprising such nucleotide sequences and host cells that comprise said nucleotide sequences or expression vectors.</p>
>> Read More

THERAPEUTIC AND DIAGNOSTIC METHODS FOR CANCER (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The present invention provides therapeutic and diagnostic methods and compositions for cancer, for example, non-small cell lung cancer (NSCLC). The invention provides methods of treating NSCLC, methods of determining whether a patient suffering from NSCLC is likely to respond to treatment comprising a PD-L1 axis binding antagonist, methods of predicting responsiveness of a patient suffering from NSCLC to treatment comprising a PD-L1 axis binding antagonist, and methods of selecting a therapy for a patient suffering from NSCLC, based on expression levels of a biomarker of the invention (e.g., PD-L1 expression levels in tumor cells and/or tumor-infiltrating immune cells).</p>
>> Read More

INHIBITORS OF LYSINE SPECIFIC DEMETHYLASE-1 (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted heterocyclic derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of lysine specific demethylase-1. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.</p>
>> Read More

PYRIDINONE COMPOUND AND USE THEREOF (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The present invention provides a compound capable of being used as an active ingredient of an anti-cancer agent. To provide an anti-cancer agent with few side effects, an object of the present invention is to provide a compound capable of selectively inhibiting the target, i.e., DOCK1, or a salt thereof. The pyridinone compound of the present invention is represented by Formula (1):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.71mm" wi="53.17mm" file="US20180028515A1-20180201-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1 </sup>and R<sup>2 </sup>are the same or different, and each represents C<sub>1-6 </sub>alkyl; and <br/> R<sup>3 </sup>is a group represented by, for example, Formula (3) below: </p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="14.99mm" wi="50.21mm" file="US20180028515A1-20180201-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005" num="0000">wherein R<sup>5 </sup>in the group represented by Formula (3) is hydrogen.</p>
>> Read More

AMINOMETHYLENE PYRAZOLONES WITH THERAPEUTIC ACTIVITY (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">A compound having the structure according to formula III</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.74mm" wi="70.78mm" file="US20180030035A1-20180201-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein: <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">X is NH or S;</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is H or (1C-4C)alkyl;</li> <li id="ul0002-0003" num="0000">R<sup>2 </sup>is (1C-4C)alkyl, phenyl or a monocyclic aromatic ring having one or more N—, O— or S— atoms in the ring, which alkyl, phenyl or aromatic ring is optionally substituted with one or more groups selected from (1C-4C)alkyl, (1C-4C)alkyloxy, halo(1C-4C)alkyl, halo(1C-4C)alkyloxy, phenyloxy, phenylthio, halogen, or nitro;</li> <li id="ul0002-0004" num="0000">R<sup>3 </sup>and R<sup>4 </sup>are each independently H, (1C-6C)alkyl, (2C-6C) alkenyl, (2C-6C)alkynyl, cyano, (3C-6C)cycloalkyl, phenyl, a monocyclic aromatic ring having one or more N—, O— or S— atoms in the ring, a monocyclic non-aromatic ring having one or more N—, O— or S— atoms in the ring, each optionally substituted with hydroxyl, (1C-4C)alkoxy, phenyl, cycloalkyl, piperidyl, piperazinyl, furyl, thienyl, pirazinyl, pyrrolyl, 2H-pyrrolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyrrolidonyl, pyrrolinyl, imidazolinyl, imidazolyl, a monocyclic aromatic ring having one or more N—, O— or S— atoms in the ring, whereby each of these optional substituents is optionally further substituted with (1C-4C)alkyl, (1C-4C)alkyloxy, halo(1C-4C)alkyl, halo(1C-4C)alkyloxy, halogen, nitro or (1C-2C)dioxol forming a ring; or</li> <li id="ul0002-0005" num="0000">R<sup>3 </sup>and R<sup>4 </sup>form together pyrrolyl, imidazolyl, pyrazolyl, pyrrolidinyl, pyrrolinylimidazolidinyl, imidazolinyl, piperidyl, piperazinylmorpholinyl, each optionally substituted with (1C-6C)alkyl, phenyl(1C-4C)alkyl, phenylketo(1C-4C)alkyl;</li> <li id="ul0002-0006" num="0000">R<sup>5 </sup>is H, Cl, F, Br, Me, NO<sub>2</sub>, t-butyl, OCF<sub>3</sub>, OCH<sub>3</sub>, CF<sub>3</sub>;</li> <li id="ul0002-0007" num="0000">R<sup>6 </sup>is H, (1C-4C)alkyl, (1C-4C)alkyloxy, halo(1C-4C)alkyl, halo(1C-4C)alkyloxy, nitro or halogen;</li> <li id="ul0002-0008" num="0000">R<sup>7 </sup>is H, F, Cl, Br, Me, NO<sub>2</sub>, t-butyl, OCF<sub>3</sub>, OCH<sub>3</sub>, CF<sub>3</sub>; or pharmaceutically acceptable addition salts thereof for use in treatments of carcinoma, in particular, to delay, prevent or reverse metastasis in prostate cancer.</li> </ul> </li> </ul> </p>
>> Read More

COMPOSITIONS AND METHODS OF TUMOR TREATMENT UTILIZING NANOPARTICLES (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The present invention is directed to a method for treating cancer intraperitoneally in a subject. The method comprises administering to said subject in need thereof an anti-cancer agent encapsulated in nanoparticles wherein nanoparticles are characterized to slowly release anti-cancer agent in a timely fashion that allows efficient killing of tumor cells. The nanoparticles described herein are characterized to slowly release anti-cancer agent at a rate of 30% or less per 24 hours based on in vitro drug dissolution study.</p>
>> Read More

Novel Formulations of a Bruton's Tyrosine Kinase Inhibitor (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">Described herein is the Bruton's tyrosine kinase (Btk) inhibitor 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one, including novel pharmaceutical formulations thereof. Also disclosed are pharmaceutical compositions that include the Btk inhibitor, as well as methods of using the Btk inhibitor, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.</p>
>> Read More

PHOSPHOLIPID COMPOSITIONS (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">Compositions involving a modified egg yolk extract for use as an effective anti-cancer agent are described. The modified egg yolk extract involves specific fractions of phosphatidylcholines and sphingomyelins modified and produced from a chemical synthesis applied to the extract that produce a beneficial effect on the inhibition of cancerous cell growth. Methods of administering these compositions are also described.</p>
>> Read More

METHOD OF PREVENTING OR REDUCING THE INCIDENCE OF ACUTE URINARY RETENTION (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The embodiments include methods of preventing or reducing the incidence of acute urinary retention in mammals susceptible to developing acute urinary retention, and to methods of reducing the incidence of clinically detected prostate cancer, using compositions containing compounds based on small peptides and a pharmaceutically acceptable carrier. The method includes, but is not limited to, administering the compounds intramuscularly, orally, intravenously, intraprostatically, intrathecally, intratumorally, intranasally, topically, transdermally, etc., either alone or conjugated to a carrier to a mammal in need thereof.</p>
>> Read More

COMPOUNDS FOR INHIBITING C-MYC/MAX/DNA COMPLEX FORMATION (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">Disclosed are novel compounds of specific chemical structures having inhibitory activity on c-Myc/Max/DNA complex formation or pharmaceutically acceptable salts thereof.</p>
>> Read More

Phosphoramidate nucleoside prodrug for treating viral diseases and cancer, processes for their preparation and their use (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The present invention pertains to chemotherapeutic agents and their use for treating viral and cancerous diseases. These compounds are inhibitors of HCV NS5B polymerase, HBV DNA polymerase and, HIV-1 reverse transcriptase (RT) inhibitor, and for treatment of hepatitis B and C infection in mammals. These compounds are also of interest for the treatment of cancer.</p> <p id="p-0002" num="0000">The phosphoramidate nucleoside prodrug of the general formula 1, a stereoisomer, isotope-enriched analogue, pharmaceutically acceptable salt, hydrate, solvate, or crystalline or polymorphic form thereof,</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.45mm" wi="53.51mm" file="US20180030080A1-20180201-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">wherein: Ar is aryl or hetaryl; R<sup>1 </sup>is H or CH<sub>3</sub>; R<sup>2 </sup>is the substituent selected from OCH<sub>2</sub>CH═CH<sub>2</sub>, OCH<sub>2</sub>CH≡CH, OCH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>OCH<sub>3</sub>,</p> <p id="p-0005" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="39.20mm" wi="52.32mm" file="US20180030080A1-20180201-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0006" num="0000">R<sup>3 </sup>is H or CH<sub>3</sub>; R<sup>4 </sup>is OH, OR<sup>5</sup>, NR<sup>6</sup>R<sup>7</sup>; R<sup>5 </sup>is C<sub>1</sub>-C<sub>4</sub>-alkyl; R<sup>6 </sup>and R<sup>7 </sup>are not necessarily the same substituents selected from H or CH<sub>3</sub>; Z═O, or NH; an arrow (→) indicates the place of substituent connection; <br/> Nuc is </p> <p id="p-0007" num="0000"><chemistry id="CHEM-US-00003" num="00003"> <img id="EMI-C00003" he="29.89mm" wi="62.82mm" file="US20180030080A1-20180201-C00003.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0008" num="0000">R<sup>8 </sup>and R<sup>9 </sup>are not necessarily the same substituents selected from H, F, Cl, CH<sub>3 </sub>or OH provided when continuous line and its accompanying dotted line (<img id="CUSTOM-CHARACTER-00001" he="2.46mm" wi="6.35mm" file="US20180030080A1-20180201-P00001.TIF" alt="custom-character" img-content="character" img-format="tif"/>) together are the single carbon-carbon (C—C) bond or R<sup>8 </sup>and R<sup>9 </sup>are hydrogen provided when continuous line and its accompanying dotted line (<img id="CUSTOM-CHARACTER-00002" he="2.46mm" wi="6.35mm" file="US20180030080A1-20180201-P00001.TIF" alt="custom-character" img-content="character" img-format="tif"/>) together are the double carbon-carbon bond (C═C); <br/> R<sup>10 </sup>is the substituent selected from R<sup>10.1</sup>-R<sup>10.5</sup>; </p> <p id="p-0009" num="0000"><chemistry id="CHEM-US-00004" num="00004"> <img id="EMI-C00004" he="131.66mm" wi="56.39mm" file="US20180030080A1-20180201-C00004.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0010" num="0000">R<sup>11 </sup>is the substituent selected from H, F, Cl, CH<sub>3</sub>, or CF<sub>3</sub>; <br/> R<sup>12 </sup>is hydrogen, C<sub>1</sub>-C<sub>4</sub>-alkyl or C<sub>3</sub>-C<sub>6</sub>-cycloalkyl; <br/> X is oxygen or ethanediyl-1,1 (C═CH<sub>2</sub>); <br/> Y is O, S, CH<sub>2</sub>, or HO—CH group provided when continuous line and its accompanying dotted line (<img id="CUSTOM-CHARACTER-00003" he="2.46mm" wi="6.35mm" file="US20180030080A1-20180201-P00001.TIF" alt="custom-character" img-content="character" img-format="tif"/>) together are the single carbon-carbon (C—C) bond or Y is CH group provided when continuous line and its accompanying dotted line (<img id="CUSTOM-CHARACTER-00004" he="2.46mm" wi="6.35mm" file="US20180030080A1-20180201-P00001.TIF" alt="custom-character" img-content="character" img-format="tif"/>) together are the double carbon-carbon bond (C═C), and compound of the general formula 1, stereoisomers, isotope-enriched analogues, pharmaceutically acceptable salts, hydrates, solvates, or crystalline or polymorphic forms thereof, wherein: <br/> Ar is aryl or hetaryl; <br/> R<sup>1 </sup>is H or CH<sub>3</sub>; <br/> R is isopropyl; <br/> Nuc is </p> <p id="p-0011" num="0000"><chemistry id="CHEM-US-00005" num="00005"> <img id="EMI-C00005" he="74.59mm" wi="48.77mm" file="US20180030080A1-20180201-C00005.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

ARYL, HETEROARYL, AND HETEROCYCLIC COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">Compounds, methods of use, and processes for making inhibitors of complement factor D comprising formula I, or a pharmaceutically acceptable salt or composition thereof wherein R<sup>12 </sup>or R<sup>11 </sup>on the A group is an aryl, heteroaryl or heterocycle (R<sup>32</sup>) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.</p>
>> Read More

INHIBITORS OF BRUTON'S TYROSINE KINASE (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">Disclosed herein are reversible and irreversible inhibitors of Bruton's tyrosine kinase (Btk). Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are describeded, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.</p>
>> Read More

SELECTIVE HDAC1 AND HDAC2 INHIBITORS (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">Provided herein are compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with HDAC activity, particularly diseases or disorders that involve activity of HDAC1 and/or HDAC2. Such diseases include cancer, sickle-cell anemia, beta-thalassemia, and HIV.</p>
>> Read More

Methods, Compounds, and Compositions for the Treatment of Angiotensin-Related Diseases (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">Disclosed are small molecule non-peptidic compounds, as well as methods and compositions for the treatment of angiotensin-related diseases and disorders, including cardiovascular diseases, metabolic diseases, gastrointestinal diseases, renal diseases, inflammatory/autoimmune diseases, neurological diseases, bone marrow diseases and cancer. In particular, the invention provides compounds, methods and compositions for the treatment of metabolic diseases and disorders, such as diabetes mellitus, diabetes-related cardiovascular disorders, diabetes-related dermal ulcerations, diabetes related hypertension, and diabetes-related ophthalmic diseases.</p>
>> Read More

TREATMENT OF CANCER WITH ANTI-LAP MONOCLONAL ANTIBODIES (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">Described herein are compositions and methods relating to LAP-binding agents, including, for example, anti-LAP antibodies, and to their use in methods of treatment of cancer. LAP-binding agents affected both systemic and intra-tumor immunity and were shown effective to treat a broad spectrum of cancer types.</p>
>> Read More

PHOSPHORAMIDATE NUCLEOSIDE PRODRUG FOR TREATING VIRAL DISEASES AND CANCER, PROCESSES FOR THEIR PREPARATION AND THEIR USE (Fri, 02 Feb 2018)
The present invention pertains to chemotherapeutic agents and their use for treating viral and cancerous diseases. These compounds are inhibitors of HCV NS5B polymerase, HBV DNA polymerase and, HIV-1 reverse transcriptase (RT) inhibitor, and for treatment of hepatitis B and C infection in mammals. These compounds are also of interest for the treatment of cancer. The phosphoramidate nucleoside prodrug of the general formula (1), a stereoisomer, isotope-enriched analogue, pharmaceutically acceptable salt, hydrate, solvate, or crystalline or polymorphic form thereof, formula (1) wherein: Ar is aryl or hetaryl; R1 is H or CH3, R2 is the substituent selected from OCH2CH=CH2, OCH2CH≡CH, OCH2CH2CH2OCH3, formula (2), formula (3) or formula (4), R3 is H or CH3; R4 is OH, OR5, NR6R7; R5 is C1-C4-alkyl; R6 and R7 are not necessarily the same substituents selected from H or CH3, Z = O, or NH; an arrow (→) indicates the place of substituent connection; Nuc is formula (5) or (6); R8 and R9 are not necessarily the same substituents selected from H, F, Cl, CH3 or OH provided when continuous line and its accompanying dotted line ( ) together are the single carbon-carbon (C-C) bond or R8 and R9 are hydrogen provided when continuous line and its accompanying dotted line ( ) together are the double carbon-carbon bond (C=C); R10 is the substituent selected from R10.1- R10.5; R10.1 R10.2 R10.4 R10.5 ; R11 is the substituent selected from H, F, CI, CH3, or CF3; R12 is hydrogen, C1-C4-alkyl or C3-C6-cycloalkyl; X is oxygen or ethanediyl-1,1 (C=CH2); Y is O, S, CH2, or HO-CH group provided when continuous line and its accompanying dotted line (formula 7) together are the single carbon-carbon (C-C) bond or Y is CH group provided when continuous line and its accompanying dotted line (formula 7) together are the double carbon-carbon bond (C=C), and compound of the general formula (1), stereoisomers, isotope-enriched analogues, pharmaceutically acceptable salts, hydrates, solvates, or crystalline or polymorphic forms thereof, wherein: Ar is aryl or hetaryl; R1 is H or CH3; R2 is isopropyl; Nuc is formula (8), (9) or (10).
>> Read More

REPURPOSING CANCER DRUGS FOR TREATMENT OF MYCOBACTERIUM (Fri, 02 Feb 2018)
The present invention is directed to the discovery that pyrazinamide, a potent anti-tuberculosis agent acts through an entirely unexpected mechanism- through inhibition of the host enzyme poly ADP ribose polymerase ("PARP"). Thus, the present invention is directed to methods of treating: mycobacterial infections (Mycobacterium), especially M. tuberculosis using a PARP inhibitor, optionally in combination with at least one additional agent useful in the treatment of a mycobacterial infection, especially tuberculosis. Pharmaceutical compositions, especially including a pharmaceutical composition in oral or inhalation dosage form, comprising a PARP inhibitor, optionally in combination with an additional anti-mycobacterial agent, especially an additional anti-tuberculosis agent represent additional embodiments of the present invention.
>> Read More

COMBINATION THERAPIES FOR TREATING CANCER (Fri, 02 Feb 2018)
This invention relates to methods and compositions for treatment of inv(16) leukemia and particularly to treatment of acute myeloid leukemia. Disclosed is a method of treating inv(16) leukemia comprising the step of administering to a subject in need thereof a therapeutically effective combination of a) a compound of the formula (1) and b) a chemotherapeutic agent selected from the group consisting of pirarubicin, aclarubicin, mitoxantrone, doxorubicin, daunorubicin, idarubicin, epirubicin, cytarabine, pharmaceutically acceptable salts and mixtures thereof. The therapeutically effective combination synergistically inhibits proliferation of inv(16) leukemia cells. This invention also relates to pharmaceutical compositions comprising a therapeutically effective combination of the compound of formula (1) and the chemotherapeutic agent and a pharmaceutically acceptable excipient.
>> Read More

PI 4-KINASE INHIBITOR AS A THERAPEUTIC FOR VIRAL HEPATITIS, CANCER, MALARIA. AUTOIMMUNE DISORDERS AND INFLAMMATION, AND A RADIOSENSITIZER AND IMMUNOSUPPRESSANT (Fri, 02 Feb 2018)
The present invention provides a plant-based flavonoid pharmaceutical composition and its synthetic for inhibition of phosphau'dylinositol-4-kinases and consequent prevention and treatment of RNA viruses including but not limited to viral hepatitis, as well as activity against cancer, malaria, autoimmune disorders and inflammation, prevent organ transplant rejection and as a radiation sensitizer. A method for isolating specific plant-based flavonoid pharmaceutical compositions from raw plant material as well as a method for synthesizing the compositions are also disclosed.
>> Read More

PROTEASE TRANSITION STATE INHIBITOR PRODRUGS (Fri, 02 Feb 2018)
Disclosed herein are protease transition state inhibitor/analogue prodrug compounds selected from the group consisting of esters, carbamates, ester phosphates, and pharmaceutically acceptable salts thereof. Compositions containing such prodrugs are also disclosed, along with methods of using such compounds therapeutically or prophylactically against calicivirus, picornavirus, and/or coronavirus infection, as well as other conditions, such as malaria, cancer, stroke, heart attack, neural degeneration, cataracts, and glaucoma through inhibition of the variety of proteases associated with progression of such conditions.
>> Read More

CONJUGATES OF HYALURONIC ACID AND ANTICANCER COMPOUNDS (Fri, 02 Feb 2018)
The present invention relates to a polymer-drug conjugate wherein the polymer is hyaluronic acid and the drug is an anticancer compound. The anticancer compound is covalently linked to the hyaluronic acid by a pH-labile boronic acid-containing linkage. These conjugates can be used for the treatment of cancer.
>> Read More

METHOD OF PREVENTING OR REDUCING THE INCIDENCE OF ACUTE URINARY RETENTION (Fri, 02 Feb 2018)
The embodiments include methods of preventing or reducing the incidence of acute urinary retention in mammals susceptible to developing acute urinary retention, and to methods of reducing the incidence of clinically detected prostate cancer, using compositions containing compounds based on small peptides and a pharmaceutically acceptable carrier. The method includes, but is not limited to, administering the compounds intramuscularly, orally, intravenously, intraprostatically, intrathecally, intratumorally, intranasally, topically, transdermally, etc., either alone or conjugated to a carrier to a mammal in need thereof.
>> Read More

SUBSTITUTED THIAZOLO-PYRIDINE COMPOUNDS AS MALT1 INHIBITORS (Fri, 02 Feb 2018)
Disclosed are compounds of the general formula (I), wherein R1-R3 are as defined herein, for use as MALT1 inhibitors in the treatment of autoimmune and inflammatory diseases or disorders. Methods of synthesizing the compounds are also disclosed. Also disclosed are pharmaceutical compositions containing a compound of the invention and a method of treating a patient for an autoimmune or an inflammatory disease or disorder, for example, a cancer, by administering a compound of the invention.
>> Read More

ANTI-PD-1 ANTIBODIES (Fri, 02 Feb 2018)
The present invention relates to anti-PD-1 antibodies, as well as use of these antibodies in the treatment of diseases such as cancer and infectious disease. These antibodies have CDRs as provided in the enclosed sequences. Also part of the invention are nucleic acids encoding these antibodies, expression vectors comprising such nucleotide sequences and host cells that comprise said nucleotide sequences or expression vectors.
>> Read More

NOVEL FUSED PYRIDINE DERIVATIVES USEFUL AS FAK/AURORA KINASE INHIBITORS (Fri, 02 Feb 2018)
This invention relates to certain novel pyrimidine derivatives of the Formula (I). The invention also relates to process for the preparation of the compound of the formula (I), pharmaceutical agents or compositions containing the compound or a method of using the compound for the treatment of proliferative diseases, such as cancer.
>> Read More

PURINE AND 3-DEAZAPURINE ANALOGUES AS CHOLINE KINASE INHIBITORS (Fri, 02 Feb 2018)
There are provided substituted purine and 3-deazapurine analogues, which modulate the activity of Choline Kinase (ChoK). The compounds of this invention are therefore useful in treating diseases caused by an altered choline metabolism, such as cancer, cell proliferative disorders, infectious diseases of different origin, immune-related disorders and neurodegenerative disorders. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions comprising these compounds.
>> Read More

N-(2-(4-((1R,3R)-3-METHYL-2,3,4,9-TETRAHYDRO-1H-PYRIDO[3,4-B]INDOL-1-YL)PHENOXY)ETHYL)PROPAN-1-AMINE DERIVATIVES AND RELATED COMPOUNDS AS SELECTIVE DOWN-REGULATORS OF THE ESTROGEN RECEPTOR FOR TREATING CANCER (Fri, 02 Feb 2018)
The specification relates to compounds of Formula (I) and to pharmaceutically acceptable salts thereof, to processes and intermediates used for their preparation, pharmaceutical compositions containing them and to the compounds of Formula (I) for use as selective down-regulators of the estrogen receptor in the treatment of cell proliferative disorders, such as cancer.
>> Read More

COMBINATION TEST FOR COLORECTAL CANCER (Fri, 02 Feb 2018)
The present invention relates to methods of detecting and/or screening for colorectal cancer (CRC), a colorectal adenoma or a polyp in a patient comprising identifying patients found to be positive for fecal occult blood and further testing for one or more additional factors. Said methods can be used to assess the suitability of a patient for colonoscopy.
>> Read More

GLYCINE METABOLISM MODULATORS AND USES THEREOF (Fri, 02 Feb 2018)
The present invention relates to a compound of general formula (I) and/or its solvates, hydrates and pharmaceutically acceptable salts, which are modulators of glycine metabolism. The present invention also relates to the methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of disorders/conditions/diseases involving, relating to or associated with glycine metabolism or a pathway where glycine decarboxylase (GLDC, or glycine cleavage system) plays a role. In a preferred embodiment the disorders/conditions/disease is cancer, inflammatory conditions, Alzheimer's disease, metabolic disorders and CNS disorders.
>> Read More

GLAUCOCALYXIN A DERIVATIVE AND PREPARATION METHOD AND APPLICATION THEREOF (Thu, 01 Feb 2018)
Provided is a glaucocalyxin A derivative, or salt thereof, as represented by the formula (I), a method for preparation of said glaucocalyxin A derivative, and a use for said glaucocalyxin A derivative in preparing pharmaceuticals for fighting autoimmune diseases and tumors, e.g. difficult-to-treat diseases such as systemic lupus erythematosus, psoriasis and triple-negative breast cancer
>> Read More

PROGESTERONE-CATIONIC LIPID HYBRID AS ANTICANCER AGENT AND THE PROCESS OF SYNTHESIS THEREOF (Thu, 01 Feb 2018)
The present invention relates to the development of the cationic progesterone compounds of formula 6 as a novel anti-tumor agent. The present invention provides a method for the preparation of novel series of progesterone derivatives of formula 6. The invention also provides information related to highly selective anti-cancer activities of these compounds in wide range of cancer cell irrespective of their progesterone receptor status. Thus, the presently disclosed cationic progesterone compounds offer a viable option as anti-cancer therapeutics.
>> Read More

THERAPEUTIC USE OF ANTI-CS1 ANTIBODIES (Thu, 01 Feb 2018)
The present disclosure is directed to antagonists of CS1 that bind to and neutralize at least one biological activity of CS1. The disclosure also includes a pharmaceutical composition comprising such antibodies or antigen-binding fragments thereof. The present disclosure also provides for a method of preventing or treating disease states, including autoimmune disorders and cancer, in a subject in need thereof, comprising administering into said subject an effective amount of such antagonists.
>> Read More

THERAPEUTIC AGENT FOR BILE DUCT CANCER (Thu, 01 Feb 2018)
The present invention provides a therapeutic agent for bile duct cancer comprising 5-((2-(4-(1-(2-hydroxyethyl)piperidin-4-yl)benzamide)pyridin-4-yl)oxy)-6-(2-methoxyethoxy)-N-methyl-1H-indole-1-carboxamide or a pharmacologically acceptable salt thereof.
>> Read More

LIPID, PROTEIN, AND METABOLITE MARKERS FOR THE DIAGNOSIS AND TREATMENT OF PROSTATE CANCER (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">Methods for diagnosing the presence of prostate cancer in a subject are provided, such methods including the detection of levels of a variety of biomarkers diagnostic of prostate cancer. The invention also provides methods of treating prostate cancer by administering a biomarker or an agent that modulates a biomarker of prostate cancer. Compositions in the form of kits and panels of reagents for detecting the biomarkers of the invention are also provided.</p>
>> Read More

NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 3 (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">Described are negative allosteric modulators of metabotropic glutamate receptor 3 (mGlu3), pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating depression, cognitive disorders, schizophrenia, Alzheimer's disease, or cancer in a subject.</p>
>> Read More

SMALL-MOLECULE INHIBITORS TARGETING DISCOIDIN DOMAIN RECEPTOR 1 AND USES THEREOF (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">Compounds of formula (I), their pharmaceutically acceptable salts and stereoisomers thereof, as well as application in effectively inhibiting the enzymatic activity of discoidin domain receptor 1 and can be used as new therapeutic agents for preventing and treating e.g. inflammation, liver fibrosis, kidney fibrosis, lung fibrosis, skin scar, atherosclerosis, and cancer. The compound of formula I is: wherein the variables are as defined herein.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.20mm" wi="69.85mm" file="US20180022730A1-20180125-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

AUTOTAXIN INHIBITORS (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">The present invention relates to compounds of formula (I): wherein R<sub>1</sub>, R<sub>2</sub>, R<sub>3</sub>, R<sub>4a</sub>, R<sub>4b</sub>, R<sub>4C</sub>, R<sub>4d</sub>, L, A, Q, W and HET are each as defined herein. The compounds of the present invention are inhibitors of autotaxin (ATX) enzyme activity. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions (e.g. fibrosis) in which ATX activity is implicated.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.85mm" wi="69.85mm" file="US20180022742A1-20180125-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

COMPOUNDS AND METHODS FOR PREVENTING OR TREATING SENSORY HAIR CELL DEATH (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">Disclosed herein are compounds, and pharmaceutical compositions that include such compounds, for preventing or treating hearing loss. The compounds and pharmaceutical compositions described herein prevent or treat hair cell death. In addition, the compounds and pharmaceutical compositions described herein protect against kidney damage in an individual receiving an aminoglycoside antibiotic. Methods of using the compounds, alone or in combination with other therapeutic agents, are also disclosed.</p>
>> Read More

ANTI-CEACAM5 ANTIBODIES AND USES THEREOF (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">The present invention discloses antibodies which bind human and <i>Macaca fascicularis </i>CEACAM5 proteins, as well as isolated nucleic acids, vectors and host cells comprising a sequence encoding said antibodies. The invention also discloses immunoconjugates comprising said antibodies conjugated or linked to a growth-inhibitory agent, and to pharmaceutical compositions comprising antibodies, or immunoconjugates of the invention. The antibodies or immunoconjugates of the invention are used for the treatment of cancer or for diagnostic purposes.</p>
>> Read More

MODULATORS OF THE P70S6 KINASE FOR USE IN THE TREATMENT OF BRAIN DISORDERS AND TRIPLE-NEGATIVE BREAST CANCER (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">The invention provides compounds for use in the treatment of a disease or condition selected from brain disorders and triple-negative breast cancer, the compounds being of the formula (1):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="61.72mm" file="US20180022735A1-20180125-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a salt or tautomer thereof;</p> <p id="p-0004" num="0000">wherein: <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">X<sup>1 </sup>is N or N<sup>+</sup>(O<sup>−</sup>);</li> <li id="ul0002-0002" num="0000">X<sup>2 </sup>is N or CH;</li> <li id="ul0002-0003" num="0000">Q is selected from a C1-3 alkylene group, cyclopropane-1,1-diyl and cyclobutane-1,1-diyl;</li> <li id="ul0002-0004" num="0000">R<sup>1 </sup>is selected from hydrogen and C<sub>1-4 </sub>alkyl;</li> <li id="ul0002-0005" num="0000">R<sup>2</sup>, R<sup>3 </sup>and R<sup>4 </sup>are the same or different and each is selected from hydrogen and fluorine;</li> <li id="ul0002-0006" num="0000">Ar<sup>1 </sup>is a benzene, thiophene, naphthyl or pyridine ring optionally substituted with 1, 2 or 3 substituents selected from fluorine; chlorine; bromine; C<sub>1-4 </sub>hydrocarbyl; C<sub>1-4 </sub>hydrocarbyloxy; trifluoromethyl; difluoromethyl; cyano; trifluoromethoxy; difluoromethoxy;</li> <li id="ul0002-0007" num="0000">Ar<sup>2 </sup>is a monocyclic 5- or 6-membered heteroaryl ring containing 1, 2 or 3 heteroatom ring members selected from O, N and S and being optionally substituted with 1, 2 or 3 substituents selected from fluorine; C<sub>1-4 </sub>hydrocarbyl; amino; mono-C<sub>1-4 </sub>hydrocarbylamino and di-C<sub>1-4 </sub>hydrocarbylamino;</li> <li id="ul0002-0008" num="0000">and wherein, in each substituent consisting of or containing C<sub>1-4 </sub>hydrocarbyl, the C<sub>1-4 </sub>hydrocarbyl is selected from C<sub>1-4 </sub>alkyl, C<sub>2-4 </sub>alkenyl, C<sub>2-4 </sub>alkynyl, cyclopropyl, cyclobutyl and cyclopropylmethyl.</li> </ul> </li> </ul> </p>
>> Read More

3-SUBSTITUTED CYCLOPENTYLAMINE DERIVATIVES (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">Compounds of the formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.13mm" wi="61.89mm" file="US20180022738A1-20180125-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which R, W, R<sup>1</sup>, R<sup>4</sup>, X<sup>1</sup>, X<sup>2</sup>, X<sup>3</sup>, X<sup>4 </sup>and q have the meanings indicated in Claim <b>1, </b> <br/> are inhibitors of fatty acid synthase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation. </p>
>> Read More

5-[[4-[[Morpholin-2-yl]Methylamino]-5-(Trifluoromethyl)-2 Pyridyl]Amino]Pyrazine-2-Carbonitrile and Therapeutic Uses Thereof (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to 5-[[4-[[morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridyl]amino]pyrazine-2-carbonitrile compounds (referred to herein as “TFM compounds”) which, inter alia, inhibit Checkpoint Kinase 1 (CHK1) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or a thymidylate synthase (TS) inhibitor; (d) a microtubule targeted agent; (e) ionising radiation; (f) an inhibitor of a mitosis regulator or a mitotic checkpoint regulator; (g) an inhibitor of a DNA damage signal transducer; or (h) an inhibitor of a DNA damage repair enzyme.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.62mm" wi="44.87mm" file="US20180022739A1-20180125-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

COMPOSITIONS OF KINASE INHIBITORS AND THEIR USE FOR TREATMENT OF CANCER AND OTHER DISEASES RELATED TO KINASES (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">The present invention relates to novel thiazole-substituted indolin-2-ones as inhibitors of CSCPK and related kinases; to methods of inhibiting cancer stem cells by using a kinase inhibitor; to pharmaceutical compositions containing such compounds; and to methods of using such compounds in the treatment of a protein kinase related disorder in a mammal; and to processes of making such compounds and intermediates thereof.</p>
>> Read More

FUSED-RING COMPOUNDS, PHARMACEUTICAL COMPOSITION AND USES THEREOF (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">This disclosure is related to a fused-ring compound of formula (I) and/or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising the fused ring compound of formula (I) and/or a pharmaceutically acceptable salt thereof, preparation methods thereof, and use thereof in modulating activity of indoleamine 2, 3-dioxygenase (IDO) and/or tryptophan 2, 3-dioxygenase (TDO). This disclosure further provides methods of treating IDO and/or TDO-associated diseases, including cancer, viral infection and autoimmune diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.92mm" wi="55.80mm" file="US20180022752A1-20180125-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

ETHER COMPOUNDS FOR TREATMENT OF COMPLEMENT MEDIATED DISORDERS (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R<sup>12 </sup>or R<sup>13 </sup>on the A group is an ether (R<sup>32</sup>) are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.</p>
>> Read More

Compounds for Treatment of Complement Mediated Disorders (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.</p>
>> Read More

USE OF A MIXTURE OF MODIFIED GLUCOSE POLYMERS FOR REDUCING TUMOR METASTASIS (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">Disclosed herein is a solution, in particular a pharmaceutically acceptable solution, comprising icodextrin and hydroxyalkyl starch (HAS) that can be used in methods of preventing metastasis formation and/or relapse by administration to a body cavity of a subject afflicted with cancer. Also disclosed is a kit comprising icodextrin and HAS in pre-weighed amounts and a pharmaceutically acceptable means of dissolving the same. Also disclosed is a device comprising a pharmaceutically acceptable solution and means for administering the same.</p>
>> Read More

SELF-ASSEMBLED TARGETED INCLUSION COMPLEXES FOR DRUG DELIVERY (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">Inclusion complexes are provided containing a targeted carrier non-covalently associated with an active agent. The targeted carrier includes an inclusion host that binds the active agent or a binding partner attached to the active agent. The targeted carrier includes a targeting moiety attached to the inclusion host or to a polymer or linker attached thereto. Pharmaceutical formulations of the inclusion complexes are provided. Methods of making the inclusion complexes and formulations thereof are provided. Methods of using the inclusion complexes and formulations are provided. In some embodiments the inclusion complex includes a progesterone or estrogen targeting moiety that targets the inclusion complex to cancer cells. The targeting can cause internalization of the active agent in the target cells. In some embodiments the active agent is an anthracycline such as doxorubicin and the target cells are cancer cells.</p>
>> Read More

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">Chemical entities that are kinase inhibitors, pharmaceutical compositions and methods of treatment of cancer are described.</p>
>> Read More

IMMUNE REGULATORY OLIGONUCLEOTIDE (IRO) COMPOUNDS TO MODULATE TOLL-LIKE RECEPTOR BASED IMMUNE RESPONSE (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">The invention provides novel immune regulatory oligonucleotides (IRO) as antagonist of TLRs and methods of use thereof. These IROs have unique sequences that inhibit or suppress TLR-mediated signaling in response to a TLR ligand or TLR agonist. The methods may have use in the prevention and treatment of cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen.</p>
>> Read More

HISTONE ACETYLTRANSFERASE ACTIVATORS AND COMPOSITIONS AND USES THEREOF (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">The invention provides pharmaceutical compositions and methods for treating cancer, neurodegenerative disorders, conditions associated with accumulated amyloid-beta peptide deposits, Tau protein levels, and/or accumulations of alpha-synuclein by administering a HAT modulator and a HDAC modulator to a subject.</p>
>> Read More

Ephrin Receptor A2 (EPHA2)-Targeted Docetaxel-Generating Nano-Liposome Compositions (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">EphA2-targeted immunoliposomes for delivering docetaxel are useful in the treatment of certain types of cancer. The immunoliposomes can include an EphA2 targeting moiety (e.g., a scFv) and encapsulate a docetaxel prodrug in a stable salt form within a liposome having an average size of about 100 nm. Novel docetaxel prodrugs suitable for loading into nanoliposomes (including immunoliposomes) are provided, along with novel and other useful EphA2 targeting moieties for preparation of EphA2-targeted doxorubicin-generating immunoliposome therapies. Pharmaceutical compositions can be prepared that include nanoliposomes encapsulating one or more docetaxel prodrugs, and/or immunoliposomes or nanoparticles comprising an EphA2 binding moiety and encapsulating one or more docetaxel prodrugs. The pharmaceutical compositions are useful for administration to a patient for the treatment of cancer.</p>
>> Read More

TRISUBSTITUTED BENZOTRIAZOLE DERIVATIVES AS DIHYDROOROTATE OXYGENASE INHIBITORS (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">The present invention provides methods for treating a cancer in a subject and for inhibiting tumor growth, metastasis or a dihydrorotate oxygenase enzyme activity of a tumor or cancer cell. At least one trisubstituted benzotriazole derivative with the formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.98mm" wi="69.85mm" file="US20180021311A1-20180125-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">is administered to the subject or is contacted with the cancer cell. Compounds of formula (I) have substituents R<sub>1</sub>, R<sub>2 </sub>and R<sub>3 </sub>which have the meanings given in the specification, and pharmaceutically acceptable salts thereof.</p>
>> Read More

ANTIPROLIFERATIVE COMPOUNDS AND METHODS OF USE THEREOF (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">Compounds of formula I for treating, preventing or managing cancer are disclosed. Also disclosed are methods of treating, preventing or managing cancer, such as leukemia, comprising administering the compounds. In certain embodiments, the method of treatment comprise administering a compound provided herein in combination with a second agent. Pharmaceutical compositions and single unit dosage forms comprising the compounds are also disclosed.</p>
>> Read More

PHARMACEUTICAL COMPOSITIONS COMPRISING N-(3,5-DIMETHOXYPHENYL)-N'-(1-METHYLETHYL)-N-[3-(1-METHYL-1H-PYRAZOL-4-YL)QUINOXALIN-6-YL]ETHANE-1,2-DIAMINE (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">The invention relates to pharmaceutical compositions comprising N-(3,5-dimethoxyphenyl)-N′-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine, or a pharmaceutically acceptable salt thereof or a solvate thereof; to processes for the preparation of said compositions and to the use of said compositions for the manufacture of a medicament for the prophylaxis of or the treatment, in particular the treatment, of diseases, e.g. cancer</p>
>> Read More

FLUOROCYCLOPENTENYLCYTOSINE METHODS OF USE (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">The disclosed subject matter provides methods using and kits comprising a compound of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.51mm" wi="56.56mm" file="US20180021338A1-20180125-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a hydrate, a solvate, or a pharmaceutically acceptable salt thereof. The disclosed subject matter further provides a method of treating one or more symptoms of cancer comprising administering to a subject in need thereof a compound of formula (I) and a process for preparing such.</p>
>> Read More

CRYSTALLINE FORM OF (S)-N-(5-((R)-2-(2,5-DIFLUOROPHENYL)-PYRROLIDIN-1-YL)-PYRAZOLO[1,5-A]PYRIMIDIN-3-YL)-3-HYDROXYPYRROLIDINE-1-CARBOXAMIDE HYDROGEN SULFATE (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">A novel crystalline form of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutical compositions containing said crystalline form and the use of said crystalline form in the treatment of pain, cancer, inflammation, neurodegenerative disease or Trypanosoma cruzi infection are disclosed. In some embodiments, the novel crystalline form comprises a stable polymorph of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate. The present invention is further directed to a process for the preparation of the novel crystalline form.</p>
>> Read More

TNFRSF-BINDING AGENTS AND USES THEREOF (Fri, 26 Jan 2018)
<p id="p-0001" num="0000">Polypeptides and agents that bind a TNF receptor superfamily protein are disclosed, particularly agents that specifically bind GITR, OX40, or CD40. The polypeptides or agents may include fusion polypeptides, particularly polypeptides comprising GITRL, OX40L, or CD40L and/or bispecific agents. Also disclosed are methods of using the polypeptides or agents for inducing and/or enhancing the immune response, as well as methods for the treatment of diseases such as cancer.</p>
>> Read More

ANTIMETASTATIC 2H-SELENOPHENO[3,2-h]CHROMENES, SYNTHESIS THEREOF, AND METHODS OF USING SAME AGENTS (Fri, 26 Jan 2018)
The present invention relates to a novel cancer metastasis preventing and curing selenopheno[h]chromene derivatives, as well as methods of their manufacturing and use in different pharmaceutical compositions for the treatment and/or prevention of primary cancer and its metastasis by administration of such substances.
>> Read More

ISOQUINOLINE DERIVATIVES AS PERK INHIBITORS (Fri, 26 Jan 2018)
The invention is directed to substituted isoquinoline derivatives and uses thereof. Specifically, the invention is directed to compounds according to Formula I and the use of compounds of Formula (I) in treating disease states: (I) wherein R1, R2, R3, R4, R5, R6, R7 and X are as defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, ather osclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
>> Read More

SOLID FORMS OF TTK INHIBITOR (Fri, 26 Jan 2018)
The present invention relates to a novel co-crystal of the compound of formula (I): (Formula (I)) wherein the co-former molecule is bisphosphate hemihydrate, to processes for the preparation of the co-crystal, to pharmaceutical compositions containing the co-crystal, to the use of such a co-crystal in the manufacture of a medicament for use in the treatment of cancer and to methods of treating such diseases in the human or animal body by administering a therapeutically effective amount of such a co-crystal.
>> Read More

TGF Beta RECEPTOR ANTAGONISTS (Fri, 26 Jan 2018)
The invention relates generally to compounds that modulate the activity of TGFβR-1 and TGFβR-2, pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.
>> Read More

HISTONE ACETYLTRANSFERASE ACTIVATORS AND COMPOSITIONS AND USES THEREOF (Fri, 26 Jan 2018)
The invention provides pharmaceutical compositions and methods for treating cancer, neurodegenerative disorders, conditions associated with accumulated amyloid-beta peptide deposits, Tau protein levels, and/or accumulations of alpha-synuclein by administering a HAT modulator and a HDAC modulator to a subject.
>> Read More

PVRIG-BINDING AGENTS AND USES THEREOF (Fri, 26 Jan 2018)
Agents that specifically bind PVRIG are disclosed. The PVRIG-binding agents may include polypeptides, antibodies, bispecific agents, and/or heterodimeric molecules. Also disclosed are methods of using the agents for enhancing the immune response and/or treatment of diseases such as cancer.
>> Read More

OLEOCANTHAL ISOLATION AND CANCER TREATMENT (Fri, 26 Jan 2018)
A method for extracting S (-)-Oleocanthal from olive oil comprising mixing a first volume of water with a second volume of olive oil to form an olive oil/water mixture; letting the olive oil/water mixture stand; removing an aqueous fraction from the olive oil/water mixture leaving a reduced S (-)-Oleocanthal containing olive oil; and filtering the aqueous fraction to create aqueous S (-)-Oleocanthal.
>> Read More

AIEGENS FOR CANCER CELL IMAGING (Fri, 26 Jan 2018)
A luminogen exhibiting aggregation induced emission is provided, wherein Tl, T2 and T3 comprise one or more polyynes as a conjugated bridge. Another AIEgen comprising a hydrophilic pydium group as a strong electron- withdrawing group, a piperazine group as an electron-donating group, and a a-cyanostilbene, wherein the AIEgen exhibits aggregation induced emission. A method of synthesizing an AIEgen and a method of labeling are also provided.
>> Read More

METHOD FOR SELECTING PATIENTS RESPONSIVE FOR CANCER TREATMENTS (Thu, 25 Jan 2018)
The present invention is directed to a method of quantifying intracellular metabolite effluxes in permeabilized cancer cells for selecting cancer patients responsive for a cancer treatment, the method comprising the steps of: a) providing a sample of cancer cells taken from a patient; b) permeabilizing said cancer cells; c) incubating said permeabilized cancer cells in a reaction medium for a period of time allowing biological activity of intracellular organelles and accumulation of metabolites produced by said activity into the reaction medium in the presence of a substrate or substrates relating to a metabolite efflux or effluxes of interest, wherein said substrates used are at least glutamine and pyruvate; d) determining the quantity of metabolites relating to said metabolite efflux or effluxes of interest accumulated in the reaction medium during step c); and e) comparing the amounts of metabolites determined in step d) to equal measurements performed on control samples of the same tissue type and assessing the aggressiveness of the cancer cells or the treatment response of the cancer cells to a drug affecting a metabolic pathway or pathways relating to said metabolite efflux or effluxes of interest.
>> Read More

SALTS OF QUINAZOLINE DERIVATIVE AND METHOD FOR PREPARING SAME (Thu, 25 Jan 2018)
The present application relates to maleates of a compound of Formula I, methods for preparing the same, pharmaceutical compositions thereof and uses thereof in the treatment of tumors, such as non-small cell lung cancer, breast cancer, and other malignant tumors.
>> Read More

OPTIMISED COMBINATION THERAPY AND USE THEREOF TO TREAT CANCER AND AUTOIMMUNE DISEASE (Thu, 25 Jan 2018)
Provided is a series of new poly-fluorosubstituted pyrazolopyrimidine compounds or salts. The compounds are Bruton's tyrosine kinase (BTK) inhibitors. The compounds have better kinase inhibition selectivity and pharmokinetic properties. Also provided is a preparation method for the compounds. Also provided is a combination therapy including the compounds in combination with another targeted drug composition or another drug. The optimised combination therapy has a cooperative effect, inhibits the existence of a tumour better than a single targeted drug, and causes certain tumours to completely disappear. The optimised combination therapy treats drug resistance and cancer recurrence of a tumour better than a single targeted drug, and the treatment cycle is shorter. The present invention also relates to a combined compound and a pharmaceutical preparation wherein said combined compound acts as an active ingredient, said pharmaceutical preparation being safer at a lower dosage and having a cooperative effect efficacy. Also provided is a method of using the compounds and a preparation thereof to treat and inhibit an autoimmune disease or illness, a heterogeneous autoimmune disease or illness, an inflammatory disease, a cancer or an illness.
>> Read More

Anti-cancer agents (Wed, 24 Jan 2018)
<p id="p-0001" num="0000">An anti-cancer agent having the formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.02mm" wi="60.20mm" file="US09873699-20180123-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein Ph is a phenyl group and Ar is an aromatic group independently selected from the group consisting of phenyl, 2-bromophenyl, 4-bromophenyl, 2-chlorophenyl, 2,4, dichlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2 methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, and 3-nitrophenyl; or a pharmaceutically acceptable salt thereof.</li> </ul> </li> </ul> </p>
>> Read More

SITE SPECIFIC DOSING OF A BTK INHIBITOR (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">Disclosed herein are formulations and methods of site specific administration of Compound (I) or a pharmaceutically acceptable salt thereof. Compound (I) is a potent BTK inhibitor and hence can be useful for the treatment of diseases such as cancer, autoimmune, and inflammatory diseases.</p>
>> Read More

CONJUGATES OF CEREBLON BINDING COMPOUNDS AND G12C MUTANT KRAS, HRAS OR NRAS PROTEIN MODULATING COMPOUNDS AND METHODS OF USE THEREOF (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">Conjugates of a cereblon-binding compound and compounds having modulatory activity against G12C mutant KRAS, HRAS or NRAS G12C proteins are provided. Methods associated with preparation and use of such conjugates, pharmaceutical compositions comprising such conjugates and methods to modulate the activity of G12C mutant KRAS, HRAS or NRAS G12C proteins for treatment of disorders, such as cancer, are also provided.</p>
>> Read More

PYRIDIC KETONE DERIVATIVES, METHOD OF PREPARING SAME, AND PHARMACEUTICAL APPLICATION THEREOF (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">Compounds for the preparation of pyridone derivatives are provided. In particular, compounds of formula (IA) are provided, wherein the variable groups are as defined in the specification. The compounds of formula (IA) can be used as intermediates in the preparation of pyridone derivatives useful as mitogen-activated protein kinase kinase (MEK) inhibitors and therapeutic agents for treating cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="56.98mm" file="US20180016236A1-20180118-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

2,4-DIOXO-QUINAZOLINE-6-SULFONAMIDE DERIVATIVES AS INHIBITORS OF PARG (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">The present invention relates to compounds of formula I that function as inhibitors of PARG (Poly ADP-ribose glycohydrolase) enzyme activity wherein R<sub>1a</sub>, R<sub>1b</sub>, R<sub>1c</sub>, R<sub>1d</sub>, R<sub>1e</sub>, W, X<sub>1</sub>, X<sub>2</sub>, X<sub>3</sub>, X<sub>4</sub>, X<sub>5</sub>, X<sub>6</sub>, X<sub>7</sub>, c are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which PARG activity is implicated.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.30mm" wi="69.85mm" file="US20180016242A1-20180118-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

QUINAZOLINE INHIBITORS OF ACTIVATING MUTANT FORMS OF EPIDERMAL GROWTH FACTOR RECEPTOR (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">The invention relates to compounds of formula (I), or a pharmaceutically acceptable salt thereof:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.44mm" wi="72.64mm" file="US20180016259A1-20180118-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">Formula (I) which possess inhibitory activity against activating mutant forms of EGFR, and are accordingly useful for their anti-cancer activity and in methods of treatment of the human or animal body. The invention also relates pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm-blooded animal such as man.</p>
>> Read More

AUTOTAXIN INHIBITORY COMPOUNDS (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">The present invention relates to compounds of formula I, wherein A<sub>1</sub>, A<sub>2</sub>, A<sub>3</sub>, R<sub>1</sub>, R<sub>2</sub>, R<sub>3</sub>, R<sub>4</sub>, R<sub>5</sub>, R<sub>6</sub>, L, Ar and Q are each as defined herein. The compounds of the present invention are inhibitors of autotaxin (ATX) enzyme activity. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions (e.g. fibrosis) in which ATX activity is implicated.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.82mm" wi="69.85mm" file="US20180016274A1-20180118-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Imidazo[1,2-a]quinoxalines and Derivatives Thereof for the Treatment of Cancer (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">The invention relates to imidazo[1,2-a]quinoxaline compounds of formula (I) for the treatment of cancer, the pharmaceutical compositions comprising said chemical compounds, and the therapeutic uses thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="45.55mm" wi="54.86mm" file="US20180016278A1-20180118-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Combinational Liposome Compositions for Cancer Therapy (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">The present invention provides methods for delivery of therapeutic agents to a subject using multi-component liposomal systems. The methods include administration of a therapeutic liposome containing an active agent, followed by a administration of an attacking liposome that induces release of the agents from the therapeutic liposome.</p>
>> Read More

THERAPEUTIC AGENT FOR BILE DUCT CANCER (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">The present invention provides a therapeutic agent for bile duct cancer comprising 5-((2-(4-(1-(2-hydroxyethyl)piperidin-4-yl)benzamide)pyridin-4-yl)oxy)-6-(2-methoxyethoxy)-N-methyl-1H-indole-1-carboxamide or a pharmacologically acceptable salt thereof.</p>
>> Read More

6-Alkynyl-pyridine Derivatives (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">6-Alkynyl-pyridine of general formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.68mm" wi="68.41mm" file="US20180015082A1-20180118-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">their use as SMAC mimetics, pharmaceutical compositions containing them, and their use as a medicaments for the treatment and/or prevention of diseases characterized by excessive or abnormal cell proliferation and associated conditions such as cancer.</p> <p id="p-0004" num="0000">An exemplary compound is</p> <p id="p-0005" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="50.97mm" wi="65.19mm" file="US20180015082A1-20180118-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

PYRIDINYL AND FUSED PYRIDINYL TRIAZOLONE DERIVATIVES (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">Disclosed are compounds of Formula 1,</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.69mm" wi="56.98mm" file="US20180015083A1-20180118-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salts thereof, wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, and R<sup>4 </sup>are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating Type I hypersensitivity reactions, autoimmune diseases, inflammatory disorders, cancer, non-malignant proliferative disorders, and other conditions associated with BTK.</p>
>> Read More

ANTIBODY-DRUG CONJUGATES (ADCS) OF KSP INHIBITORS WITH AGLYCOSYLATED ANTI-TWEAKR ANTIBODIES (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">The present application relates to novel binder drug conjugates (ADCs), to active metabolites of these ADCs, to processes for preparing these ADCs, to the use of these ADCs for the treatment and/or prophylaxis of diseases and to the use of these ADCs for preparing medicaments for treatment and/or prophylaxis of diseases, in particular hyperproliferative and/or angiogenic disorders such as, for example, cancer diseases. Such treatments can be effected as monotherapy or else in combination with other medicaments or further therapeutic measures.</p>
>> Read More

Compositions And Methods For In Vivo Imaging (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">This document relates to compounds useful for targeting PARP1. Also provided herein are methods for using such compounds to detect and image cancer cells.</p>
>> Read More

TGR5 Modulators and Methods of Use Thereof (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">The invention relates to compounds of Formula A:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.32mm" wi="70.70mm" file="US20180016295A1-20180118-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a salt, solvate, hydrate, or prodrug thereof. The compounds of Formula A are TGR5 modulators useful for the treatment of various diseases, including metabolic disease, inflammatory disease, liver disease, autoimmune disease, cardiac disease, kidney disease, cancer, and gastrointestinal disease.</p>
>> Read More

Peptides for Treating Cancer (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">The invention relates to novel peptides having an HDM-2 targeting sequence that target the human minute binding protein-2. The invention also relates to fusion proteins comprising a HDM-2 targeting sequence. The invention also relates to methods of using the peptides to treat cancer.</p>
>> Read More

ANTIBODIES AGAINST TIM3 AND USES THEREOF (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">Provided herein are antibodies, or antigen-binding portions thereof, that bind to T-cell immunoglobulin and mucin-domain containing-3 (TIM3) protein. Also provided are uses of these antibodies, or antigen-binding portions thereof, in therapeutic applications, such as treatment of cancer. Further provided are cells that produce the antibodies, or antigen-binding portions thereof, polynucleotides encoding the heavy and/or light chain regions of the antibodies, or antigen-binding portions thereof, and vectors comprising the polynucleotides encoding the heavy and/or light chain regions of the antibodies, or antigen-binding portions thereof.</p>
>> Read More

Method for selecting patients responsive for cancer treatments (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">The present invention is directed to a method of quantifying intracellular metabolite effluxes in permeabilized cancer cells for selecting cancer patients responsive for a cancer treatment, the method comprising the steps of: a) providing a sample of cancer cells taken from a patient; b) permeabilizing said cancer cells; c) incubating said permeabilized cancer cells in a reaction medium for a period of time allowing biological activity of intracellular organelles and accumulation of metabolites produced by said activity into the reaction medium in the presence of a substrate or substrates relating to a metabolite efflux or effluxes of interest, wherein said substrates used are at least glutamine and pyruvate; d) determining the quantity of metabolites relating to said metabolite efflux or effluxes of interest accumulated in the reaction medium during step c); and e) comparing the amounts of metabolites determined in step d) to equal measurements performed on control samples of the same tissue type and assessing the aggressiveness of the cancer cells or the treatment response of the cancer cells to a drug affecting a metabolic pathway or pathways relating to said metabolite efflux or effluxes of interest.</p>
>> Read More

SUBSTITUTED PYRIDAZINE CARBOXAMIDE COMPOUNDS (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">The new pyridazine derivatives have unexpected drug properties as inhibitors of protein kinases especially against ALK and are useful in treating disorders related to abnormal protein kinase activities such as cancer, neurological and psychiatric diseases.</p>
>> Read More

USE OF INHIBITORS OF BRUTON'S TYROSINE KINASE (BTK) (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">Disclosed herein are methods for treating a cancer comprising: a. administering a Btk inhibitor to a subject sufficient to result in an increase or appearance in the blood of a subpopulation of lymphocytes defined by immunophenotyping; b. determining the expression profile of one or more biomarkers from one or more subpopulation of lymphocytes; and c. administering a second agent based on the determined expression profile.</p>
>> Read More

GLUTHATIONE / GOLD(III) PHARMACEUTICAL COMPOSITION (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">A method for treating cancer and gold(III) complexes with diaminocyclohexane ligand as anticancer agents. Also described are a pharmaceutical composition incorporating the gold(III) complexes and a method of synthesizing the gold(III) complexes.</p>
>> Read More

COMPOUNDS FOR REDUCING C-MYC IN C-MYC OVEREXPRESSING CANCERS (Fri, 19 Jan 2018)
The invention relates to new compounds that reduce c-Myc expression and useful for cancer treatment, particularly hematological cancers such as aggressive B- and T-cell lymphomas. The new compounds may be combined with adjunct c-Myc inhibor agents such as a PI3K inhibitor, CK-1 inhibitor, Akt-inhibitor, proteasome inhibitor and/or mTor inhibitor. The c-Myc reducing agent may be provided as a lead-in treatment to reduce or initiate reduction of c-Myc prior to adminstration of the adjunct cancer therapeutic agent. Treatment with a c-Myc reducing agent modulates the disease state of the c-Myc overexpressing cancer making it less malignant and more susceptible to adjunctive cancer therapies.
>> Read More

ANTIBODIES AGAINST TIM3 AND USES THEREOF (Fri, 19 Jan 2018)
Provided herein are antibodies, or antigen-binding portions thereof, that bind to T-cell immunoglobulin and mucin-domain containing-3 (TIM3) protein. Also provided are uses of these antibodies, or antigen-binding portions thereof, in therapeutic applications, such as treatment of cancer. Further provided are cells that produce the antibodies, or antigen-binding portions thereof, polynucleotides encoding the heavy and/or light chain regions of the antibodies, or antigen-binding portions thereof, and vectors comprising the polynucleotides encoding the heavy and/or light chain regions of the antibodies, or antigen-binding portions thereof.
>> Read More

ISO-CITRATE DEHYDROGENASE (IDH) INHIBITOR (Fri, 19 Jan 2018)
Disclosed are compounds inhibiting the conversion of α–KG to D-2-HG, pharmaceutically acceptable salts, hydrates, solvates or stereoisomers thereof and pharmaceutical compositions comprising the compounds. The compound and the pharmaceutical composition can effectively treat IDH associated diseases, including cancer.
>> Read More

ISO-CITRATE DEHYDROGENASE (IDH) INHIBITOR (Fri, 19 Jan 2018)
Disclosed are compounds inhibiting the conversion of α–KG to D-2-HG, pharmaceutically acceptable salts, hydrates, solvates or stereoisomers thereof and pharmaceutical compositions comprising the compounds. The compounds and pharmaceutical compositions can effectively treat IDH associated diseases, including cancer.
>> Read More

PYRIMIDINONE DERIVATIVES AND USES THEREOF TO NEUTRALIZE THE BIOLOGICAL ACTIVITY OF CHEMOKINES (Fri, 19 Jan 2018)
A subject of the present invention is a compound having the general formula (I) a pharmaceutically acceptable salt thereof or a tautomeric form thereof, wherein A, B3, B4, B5, Y, X, B1 and B2 are as defined in any one of claims 1 to 10. Another subject of the invention is the compound as defined above for use as a medicament, in particular for preventing and/or treating inflammation and inflammatory diseases, immune and auto-immune diseases, pain related diseases, genetic diseases and/or cancer.
>> Read More

NEW 1,2,4-TRIAZOLO-[3,4-b]-1,3,4-THIADIAZOLE DERIVATIVES (Fri, 19 Jan 2018)
Derivatives of 1,2,4-Triazolo-[3,4-b]-1,3,4-thiadiazoles according to formula (I), processes for their production, pharmaceutical compositions containing them and their use in the treatment of cancer.
>> Read More

WEE-1 INHIBITING PYRAZOLOPYRIMIDINONE COMPOUNDS (Fri, 19 Jan 2018)
The present invention relates to compounds that are useful as inhibitors of the activity of Wee-1 kinase. The present invention also relates to pharmaceutical compositions comprising these compounds and to methods of using these compounds in the treatment of cancer and methods of treating cancer.
>> Read More

WEE-1 INHIBITING PYRIDOPYRIMIDINONE COMPOUNDS (Fri, 19 Jan 2018)
The present invention relates to compounds that are useful as inhibitors of the activity of Wee-1 kinase. The present invention also relates to pharmaceutical compositions comprising these compounds and to methods of using these compounds in the treatment of cancer and methods of treating cancer.
>> Read More

PYRAZOLYLAMINOBENZIMIDAZOLE DERIVATIVES AS JAK INHIBITORS (Fri, 19 Jan 2018)
The present invention provides compounds of the formula below (I'): where R, and R1-R3 are as described herein, methods of treating patients for certain types of autoimmune diseases and cancer, and processes for preparing the compounds.
>> Read More

METHODS FOR TREATING PTEN DEFICIENT EPITHELIAL CANCERS USING A COMBINATION OF ANTI-PI3KBETA AND ANTI-IMMUNE CHECKPOINT AGENTS (Fri, 19 Jan 2018)
The present invention relates to methods for treating PTEN deficient epithelial cancers using a combination of anti-PI3Kbeta and anti-immune checkpoint agents.
>> Read More

BI-DOTA COMPLEX-LOADED DENDRITIC POLYMER NANOPARTICLES (Fri, 19 Jan 2018)
Disclosed are compositions comprising polymeric nanoparticles and methods of using the same. The polymeric nanoparticles can be conjugated with a targeting ligand that is a substrate for a solid tumor-specific cell protein. The polymeric nanoparticles can also comprises an imaging compound and/or a therapeutic agent encapsulated in the hydrophobic interior of the nanoparticle. A cancer therapeutic composition comprising the nanoparticle is also disclosed. The disclosed nanoparticles can be used to target and deliver imaging and/or therapueitc compounds to cancer cells, thereby identifying and/or treating a solid tumor cell target. Methods for treating cancer, such as lung cancer, using the polymeric nanoparticles are also disclosed.
>> Read More

BIOMARKERS PREDICTIVE OF ENDOCRINE RESISTANCE IN BREAST CANCER (Fri, 19 Jan 2018)
The present invention is based on the identification of novel biomarkers predictive of endocrine resistance in breast cancer.
>> Read More

COMPOUNDS AND METHODS FOR THE PREVENTION AND TREATMENT OF TUMOR METASTASIS AND TUMORIGENESIS (Fri, 19 Jan 2018)
The disclosure provides compounds for reducing the prevalence of the perinucleolar compartment in cells, for example, of formula (I), wherein RI, R2, R3, and R4 are as defined herein, that are useful in treating a disease or disorder associated with increased prevalence of the perinucleolar compartment, such as cancer. Also disclosed is a composition containing a pharmaceutically acceptable carrier and at least one compound embodying the principles of the invention, and a method of treating or pre venting cancer in a mammal.
>> Read More

N-PHENYL-N'-PHENOXYCARBONYL-PHENYLSULFONHYDRAZIDE DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING SAME (Thu, 18 Jan 2018)
The present invention relates to a N -phenyl- N' -phenoxycarbonyl-phenylsulfonhydrazide derivative with excellent inhibitory activity on PGE 2 production, a method for preparing the same and a pharmaceutical composition comprising the same as an active ingredient. The present N -phenyl- N' -phenoxycarbonyl-phenylsulfonhydrazide derivative may be used effectively for preventing or treating inflammation, arthritis, high fever, pain, cancer, stroke or bone disease.
>> Read More

NOVEL CONDENSED PYRIMIDINE COMPOUND OR SALT THEREOF (Thu, 18 Jan 2018)
The problem to be solved by the present invention is to provide a novel compound having RET inhibitory activity. The present invention also provides a pharmaceutical preparation that is useful for the prevention and/or treatment of RET-related diseases, particularly cancer, based on RET inhibitory activity. The present invention provides a compound represented by Formula (I) : wherein A, R 2 , and X are as defined in the specification; or a salt thereof.
>> Read More

PROTEIN TYROSINE KINASE MODULATORS AND METHODS OF USE (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">Heterocyclic pyrimidine compounds that modulate mutant-selective epidermal growth factor receptor (EGFR) and ALK kinase activity are disclosed. More specifically, the invention provides pyrimidines which inhibit, regulate and/or modulate kinase receptor, particularly in selectively modulation of various EGFR mutant activity and ALK kinase activity have been disclosed. Pharmaceutical compositions comprising the pyrimidine derivative, and methods of treatment for diseases associated with protein kinase enzymatic activity, particularly EGFR or ALK kinase activity including non-small cell lung cancer comprising administration of the pyrimidine derivative are disclosed.</p>
>> Read More

QUINAZOLINE AND QUINOLINE COMPOUNDS AND USES THEREOF (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">This invention provides compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein T, J, R, R<sup>4</sup>, R<sup>q</sup>, o, R<sup>A</sup>, W and R<sup>B </sup>and subsets thereof are as described in the specification. The compounds are inhibitors of NAMPT and are thus useful for treating cancer, inflammatory conditions, and/or T-cell mediated autoimmune disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="65.53mm" file="US20180009784A1-20180111-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

HETEROCYCLIC COMPOUNDS AND USE THEREOF (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">Heterocyclic compounds of Formula (I) shown herein. Also disclosed are pharmaceutical compositions containing the heterocyclic compounds and methods of using the heterocyclic compounds to mobilize hematopoietic stem cells and endothelial progenitor cells into the peripheral circulation. Further provided are methods for treating tissue injury, cancer, inflammatory disease, and autoimmune disease with the heterocyclic compounds.</p>
>> Read More

CHROMENONE INHIBITORS OF MONOCARBOXYLATE TRANSPORTERS (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">The invention provides compounds effective as inhibitors of monocarboxylate transporters such as MCT1 and MCT4, which can be used for treatment of medical conditions wherein treatment of the condition with a compound having an inhibitor effect on MCT1, MCT4, or both is medically indicated. Compounds of the invention can have antitumor, antidiabetes, anti-inflammatory, or immunosuppressive pharmacological effects, and can be effective for treatment of cancer and of type II diabetes.</p>
>> Read More

Resorcinol Derivative As HSP90 Inhibitor (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">The present invention relates to a compound represented by formula (I) of a resorcinol derivative as an HSP90 inhibitor or pharmaceutically accepted salts thereof. The compound in the present invention has the activity of inhibiting heat shock protein HSP90. Therefore, the compound in the present invention is used to treat proliferative diseases such as cancer and neurodegenerative diseases. The present invention further provides the compounds and preparation methods for pharmaceutical compositions comprising the compounds, a method for treating diseases, and pharmaceutical compositions comprising the compounds.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.27mm" wi="69.85mm" file="US20180009794A1-20180111-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

FUROQUINOLINEDIONES AS INHIBITORS OF TDP2 (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">Compounds of Formula I and the pharmaceutically acceptable salts thereof are disclosed Formula I. The variables X<sup>1</sup>, X<sup>2</sup>, and R<sup>1-4 </sup>are disclosed herein. The compounds are useful for treating cancer and related proliferative diseases. Pharmaceutical compositions containing compounds of Formula I and methods of treatment comprising administering compounds of Formula I are also disclosed.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.97mm" wi="59.27mm" file="US20180009822A1-20180111-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

TREATMENT OF CANCER WITH ANTI-LAP MONOCLONAL ANTIBODIES (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">Described herein are compositions and methods relating to LAP-binding agents, including, for example, anti-LAP antibodies, and to their use in methods of treatment of cancer. LAP-binding agents affected both systemic and intra-tumor immunity and were shown effective to treat a broad spectrum of cancer types.</p>
>> Read More

MACROMOLECULAR TRANSITION METAL COMPLEXES FOR TREATMENT OF CANCERAND PROCESS FOR THEIR PREPARATION (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">The present invention relates to macromolecular transition metal complexes, characterized by having the general formula (I), to the process for their preparation, and to bidentate and monodentate macroligands. The invention also refers to pharmaceutical compositions and medicaments containing said macromolecular transition metal complexes, and to the use of said pharmaceutical compositions, medicaments and macromolecular transition metal complexes for cancer therapy and/or cancer prevention, as antitumor agent in solid tumors, liquid tumors and/or metastases and/or as radiosensitizer agents.</p>
>> Read More

DELIVERY, USE AND THERAPEUTIC APPLICATIONS OF THE CRISPR-CAS SYSTEMS AND COMPOSITIONS FOR MODELING COMPETITION FO MULTIPLE CANCER MUTATIONS IN VIVO (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">The invention involves inducing 3-50 or more mutations (e.g., any whole number between 3 and 50 of mutations, with it noted that in some embodiments there can be up to 16 different RNA(s), e.g., sgRNAs each having its own a promoter, in a vector, such as AAV, and that when each sgRNA does not have its own promoter, there can be twice to thrice that amount of different RNA(s), e.g., sgRNAs, e.g., 32 or even 48 different guides delivered by one vector) in transgenic Cas9 eukaryotes to model genetic disease, e.g. cancer. The invention comprehends testing putative treatments with such models, e.g., testing putative chemical compounds that may be pharmaceutically relevant for treatment or gene therapy that may be relevant for treatment, or combinations thereof. The invention allows for the study of genetic diseases and putative treatments to better understand and alleviate a genetic disease or a condition, e.g., cancer.</p>
>> Read More

METHODS TO INDUCE TARGETED PROTEIN DEGRADATION THROUGH BIFUNCTIONAL MOLECULES (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof.</p>
>> Read More

Inhibitors of Beta-Hydroxylase for Treatment of Cancer (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">The present invention relates to compounds which modulate (e.g., inhibit) the activity of beta-hydrolase (e.g., ASPH), including novel 2-aryl-5-amino-3(2H)-furanone and 2-heteroaryl-5-amino-3(2H)-furanone compounds, pharmaceutical compositions thereof, methods for their synthesis, and methods of using these compounds to modulate the activity of ASPH in an a cell-free sample, a cell-based assay, and in a subject. Other aspects of the invention relate to use of the compounds disclosed herein to ameliorate or treat cell proliferation disorders.</p>
>> Read More

CRYSTALLINE (8S,9R)-5-FLUORO-8-(4-FLUOROPHENYL)-9-(1-METHYL-1H-1,2,4-TRIAZOL-5-YL)-8,9-DIHYDRO-2H-PYRIDO[4,3,2-DE]PHTHALAZIN-3(7H)-ONE TOSYLATE SALT (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">Provided herein are (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt forms, including crystalline forms, arid methods of their preparation. Pharmaceutical compositions comprising a (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt are also provided, as are methods of using (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt to treat a disease or condition, such as a cancer.</p>
>> Read More

BICYCLIC FUSED PYRIMIDINE COMPOUNDS AS TAM INHIBITORS (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">This application relates to compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="57.49mm" file="US20180009815A1-20180111-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salts thereof, which are inhibitors of TAM kinases which are useful for the treatment of disorders such as cancer.</p>
>> Read More

NANOPARTICLE CONJUGATES OF HIGHLY POTENT TOXINS AND INTRAPERITONEAL ADMINISTRATION OF NANOPARTICLES FOR TREATING OR IMAGING CANCER (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">Disclosed are methods of treating cancer of the intraperitoneal cavity using compositions comprising nanoparticles without targeting agents. In addition, nanoparticles are described that comprise a highly toxic anticancer agent (e.g., an anticancer agent having an IC<sub>50 </sub>less than 1 nM) covalently bound via a linker to a triblock copolymer. Other nanoparticles that comprise Pt(IV) and an anticancer agent are also described. Also disclosed are nanoparticles comprising imaging agents non-covalently associated with a polymer, and methods of imaging cancer of the intraperitoneal cavity using compositions comprising nanoparticles without targeting agents.</p>
>> Read More

NON-TOXIC FORMULATIONS OF RADIO-LUMINESCENT NANOPARTICLES FOR USE AS CANCER RADIO-SENSITIZING AGENTS (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">The invention relates generally to a formulation in which metal tungstate or metal molybdate particles are encapsulated within biocompatible, diseased cell-targeting polymeric coatings. Such formulations render metal tungstate or metal molybdate particles suitable for in vivo biomedical imaging and therapeutic applications.</p>
>> Read More

METHOD FOR TREATING MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF)-IMPLICATED DISEASES AND CONDITIONS WITH IODO PYRIMIDINE DERIVATIVES (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">Compounds useful for the inhibition of macrophage migration inhibitory factor (MIF) are provided herein, having the Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="18.63mm" wi="20.83mm" file="US20180009764A1-20180111-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein A is selected from the group consisting of aromatic or non-aromatic rings, bicyclic rings, polycyclic rings, alkenes or alkynes; B is H, OH, OR, SR, NH<sub>2</sub>, NHR, or alkyl; R is H or alkyl, and X and Y are independently N or CH, but one of X and Y must be N. Also provided are pharmaceutical compositions that contain a Formula I compound and methods for the treatment of MIF-implicated diseases or conditions that include administering a safe and effective amount of a Formula I compound.</p>
>> Read More

Highly Selective Anti-Cancer Agents Targeting Non-Small Cell Lung Cancer and Other Forms of Cancer (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">Described herein are analogues of 2-methyl-3-(2-ethynylthiazol-4-yl)cyclopent-2-enol and the corresponding ketone 3-(2-ethynylthiazol-4-yl)-2-methylcyclopent-2-enone, the analogues having terminal alkyne groups at the 2-position of the thiazole ring. These drug-like molecules, referred to as CETZOLE compounds, are useful to treat non-small cell lung cancer and other forms of cancer. Methods of making and using the compounds, methods of treating various diseases, pharmaceutical compositions, and kits are also disclosed.</p>
>> Read More

INHIBITORS OF TRKA KINASE (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">The present invention is directed to the compounds of Formula I which are inhibitors of tropomyosin-related kinase A (TrkA): Formula (I) or steroisomers, tautomers or a pharmaceutically acceptable salts, metabolites, isotopes, solvates or prodrugs thereof, wherein, Ra, Rb, Rc, Rd, R1, R2, L and Het-Ar are as defined herein. These compounds can be used for the preventive and/or therapeutic treatment of diseases or disorders associated with abnormal activities of nerve growth factor (NGF) receptor TrkA such as Pain, inflammation or an inflammatory diseases, Cancer, atherosclerosis, restenosis, thrombosis, Neurodegenerative diseases, Erectile Dysfunction (ED), Skin disorders, Autoimmune disease like Multiple sclerosis, Sjögren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis, Infectious diseases, diseases related to an imbalance of the regulation of bone remodeling, endometriosis, pelvic pain syndrome and diseases resulting from abnormal tissue remodelling and fibrotic disorders; or a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.13mm" wi="69.85mm" file="US20180009781A1-20180111-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

NOVEL FUSED PYRIMIDINE COMPOUND OR SALT THEREOF (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">The problem to be solved by the present invention is to provide a novel compound having RET inhibitory activity. The present invention also provides a pharmaceutical preparation that is useful for the prevention and/or treatment of RET-related diseases, particularly cancer, based on RET inhibitory activity. The present invention provides a compound represented by Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="26.25mm" wi="27.26mm" file="US20180009818A1-20180111-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein A, R<sup>2</sup>, and X are as defined in the specification; or a salt thereof.</p>
>> Read More

HETEROCYCLIC COMPOUNDS AS PI3K-y INHIBITORS (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">This application relates to compounds of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="42.76mm" wi="55.37mm" file="US20180009816A1-20180111-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salts or stereoisomers thereof, which are inhibitors of PI3K-γ which are useful for the treatment of disorders such as autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.</p>
>> Read More

PTERIDINE DIONE MONOCARBOXYLATE TRANSPORTER INHIBITORS (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">The invention provides compounds effective as inhibitors of monocarboxylate transporters such as MCT1 and MCT4, which can be used for treatment of medical conditions wherein treatment of the condition with a compound having an inhibitor effect on MCT1, MCT4, or both is medically indicated. Compounds of the invention can have antitumor, antidiabetes, anti-inflammatory, or immunosuppressive pharmacological effects, and can be effective for treatment of cancer and of type II diabetes.</p>
>> Read More

BICYCLIC HETEROCYCLES AS FGFR4 INHIBITORS (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">The present disclosure relates to bicyclic heterocycles, and pharmaceutical compositions of the same, that are inhibitors of the FGFR4 enzyme and are useful in the treatment of FGFR4-associated diseases such as cancer.</p>
>> Read More

ENZALUTAMIDE DERIVATIVES FOR THE TREATMENT OF PROSTATE AND BREAST CANCER (Fri, 12 Jan 2018)
The invention provides a compound of formula (I) or (I') or a pharmaceutically acceptable salt thereof. Also provided are pharmaceutical compositions comprising the compounds, processes for preparing the compounds and medical uses of the compounds.
>> Read More

4-ANILINO-QUINOLINE COMPOUNDS AS ANTI-CANCER AGENTS (Fri, 12 Jan 2018)
The present invention relates to a compound of general formula (I): said compound being as defined in claim (1). The invention also relates to a pharmaceutical composition comprising: -a compound of general formula (I) as defined in claim (12) and, -at least one antibody selected from an anti-PD1antibody, an anti-CTLA4 antibody, an anti-PD-L1 antibody and a mixture of two or more thereof. The invention also relates to a compound of general formula (I) as defined in claim (17) for use in the treatment of cancer, said cancer being preferably selected from melanoma, bladder, kidney, prostate, colon, lung, breast and blood cancer.
>> Read More

SULFATED GLYCOPOLYMERS (Fri, 12 Jan 2018)
This invention relates to sulfated glycopolymers comprising a polymeric backbone wherein at least one of the monomeric units which form the backbone has a pendant galactose and/or N-acetyl galactosamine group, wherein one or more of the pendant galactose groups are sulfated at one or more of positions 2, 3, 4 and 6 and/or one or more of the N-acetyl galactosamine groups are sulfated at one or more of positions 3, 4 and 6. The invention also relates to the use of sulfated glycopolymers in the treatment of a disease, for example, IRI, acute kidney injury, myocardial ischaemia, ischaemic stroke, cancer or an autoimmune disease.
>> Read More

A CHEMICAL COMPOUND FOR INHIBITING THE GROWTH AND PROLIFERATION OF HUMAN LIVER CANCER CELLS HEPG2 AND METHOD FOR SYNTHESIZING IT (Fri, 12 Jan 2018)
The compound 2-((4-Nitrophenyl)amino)-7,8,9,10-tetrahydrocyclohepta[4,5]thieno[2,3-d][1,3,4]thiadiazolo[3,2-a]pyrimidin-11(6H)-one and method of synthesizing it, wherein the compound is effective to inhibit the growth and proliferation of human liver cancer cells HepG2. The compound has a higher efficiency to inhibit the growth and proliferation of these cells as it has an inhabitation concentration value (IC50) of 0.7 μg, compared to reference medication Doxorubicin that has an (IC50) value of 1.2 μg. It further surpasses that reference medication at all tested concentrations. The method includes the steps of: preparing a first compound of cycloheptanone, ethylcyanoacetate, sulfur, ethanol and diethylamine; preparing a second compound by heating of the first compound with hydrazine hydrate in absolute ethanol as solvent; preparing a third compound by heating the second compound with carbon disulphide in pyridine; and preparing the compound of the invention by reacting the third compound with 4-nitrophenylisothiocyanate in dimethylformamide as solvent.
>> Read More

COMBINATION OF A PD-l ANTAGONIST AND A RAF INHIBITOR FOR TREATING CANCER (Fri, 12 Jan 2018)
Disclosed herein is a pharmaceutical combination for use in the prevention, delay of progression or treatment of cancer, wherein the pharmaceutical combination exhibits a synergistic efficacy. The pharmaceutical combination comprises a humanized antagonist monoclonal antibody against PD- and a RAF inhibitor. Also disclosed herein is a combination for use in the prevention, delay of progression or treatment of cancer in a subject, comprising administering to the subject a therapeutically effective amount of a humanized antagonist monoclonal antibody against PD-1 and a therapeutically effective amount of a RAF inhibitor.
>> Read More

NOVEL THIAZOLO[5,4-D]PYRIMIDINE DERIVATIVES AS INVERSE AGONISTS OF A2A ADENOSINE RECEPTORS (Fri, 12 Jan 2018)
The present invention refers to novel thiazolo[5,4-d]pyrimidine derivatives that are inverse agonists of the adenosine A2A receptor, to a process for their preparation, to the pharmaceutical compositions containing them and to their use in the medical field, in particular in the therapeutic treatment of diseases or disorders associated to an activity of the adenosine A2A receptor, and more in particular in the therapeutic treatment of neurological diseases, of pain, of cancer, and of dermal fibrosis and scarring.
>> Read More

1,3-DIHYDROXY-PHENYL DERIVATIVES USEFUL AS IMMUNOMODULATORS (Fri, 12 Jan 2018)
The present disclosure generally relates to compounds of formula (I), wherin R2 is a phenyl or pyridinyl moiety, useful as immunomodulators. Provided herein are compounds, compositions comprising such compounds, and methods of their use. The disclosure further pertains to pharmaceutical compositions comprising at least one compound according to the disclosure that are useful for the treatment of various diseases, including cancer and infectious diseases.
>> Read More

BICYCLIC UREA KINASE INHIBITORS AND USES THEREOF (Fri, 12 Jan 2018)
The present disclosure provides compounds of Formula (I), (II), and (III). The provided compounds are able to bind protein kinases (e.g., SIK) and may be useful in modulating (e.g., inhibiting) the activity of a protein kinase (e.g., SIK, (e.g., SIK1, SIK2, or SIK3)) in a subject or cell. The provided compounds may be useful in treating or preventing a disease (e.g., proliferative disease, musculoskeletal disease, genetic disease, hematological disease, neurological disease, painful condition, psychiatric disorder, or metabolic disorder) in a subject in need thereof. Also provided are pharmaceutical compositions, kits, methods, and uses that include or involve a compound described herein.
>> Read More

LIPID, PROTEIN, AND METABOLITE MARKERS FOR THE DIAGNOSIS AND TREATMENT OF PROSTATE CANCER (Fri, 12 Jan 2018)
Methods for diagnosing the presence of prostate cancer in a subject are provided, such methods including the detection of levels of a variety of biomarkers diagnostic of prostate cancer. The invention also provides methods of treating prostate cancer by administering a biomarker or an agent that modulates a biomarker of prostate cancer. Compositions in the form of kits and panels of reagents for detecting the biomarkers of the invention are also provided.
>> Read More

SUBSTITUTED PYRIMIDINE COMPOUNDS AS PHOSPHATIDYLINOSITOL 3-KINASE DELTA INHIBITOR AND USE THEREOF (Thu, 11 Jan 2018)
The present invention belongs to the field of medicinal chemistry, and relates to substituted pyrimidine compounds as phosphatidylinositol 3-kinase (PI3K) ´ inhibitor and a use thereof. In particular, the present invention provides a compound as shown by formula I or an isomer, pharmaceutically acceptable salt, solvate or prodrug thereof, the preparation methods of same and pharmaceutical compositions containing these compounds and a use of these compounds or compositions for treating cancer, hyperblastosis diseases or inflammatory diseases. The compounds of the present invention have a good inhibiting activity on PI3K´ and have a high selectivity. It is hoped that these will be therapeutic agents for cancer, hyperblastosis diseases or inflammatory diseases.
>> Read More

APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES (Thu, 11 Jan 2018)
Disclosed are compounds (I) which inhibit the activity of anti-apoptotic Bcl-xL proteins, compositions containing the compounds and compounds (I) for use in the methods of treating diseases during which is expressed anti-apoptotic Bcl-xL protein.
>> Read More

PROTEIN ARGININE N-METHYLTRANSFERASES INHIBITORS AND USES THEREOF (Thu, 11 Jan 2018)
The present invention relates to a compound of following formula (I): or a pharmaceutically acceptable salt and/or solvate thereof, notably for use thereof as a drug, notably in the treatment of cancer, or as a PRMT inhibitor. The present invention relates also to a pharmaceutical composition containing such a compound and to a method for the preparation of such a compound.
>> Read More

Cleavable polymer drug conjugates (Thu, 11 Jan 2018)
Polymer-drug conjugates according to formula I below are disclosed as are methods of preparing said polymer-drug conjugates and their use in the treatment of diseases such as cancer, wherein A, B, R1, R2, R3, x, y, n, L and D are as defined therein. Also disclosed are precursor conjugates of the aforementioned polymer-drug conjugates.
>> Read More

AGENT FOR CONTROLLING CELLS CONSTITUTING CANCER MICROENVIRONMENT OR INFLAMMATORY MICROENVIRONMENT (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">An agent according to the present invention comprises as an effective component any of (1) disulfiram, diethyldithiocarbamate, or a metal complex of diethyldithiocarbamate; (2) a pharmaceutically acceptable salt of (1); or (3) a solvate of (1) or (2), and is used for inhibition of interaction between CR2B or CCR5 and FROUNT protein, inhibition of macrophages, control of cells constituting a cancer microenvironment or inflammatory microenvironment, or enhancement of anticancer activity of an anticancer drug. It is also possible to provide a compound with a reduced side effect and an increased pharmacological effect by identifying a disulfiram derivative having a lower aldehyde dehydrogenase-inhibiting activity and a higher FROUNT-inhibiting activity among derivatives prepared by structural modification of disulfiram.</p>
>> Read More

ZINC COMPLEXES OF HYDRAZONES AND (THIO)SEMICARBAZONES AND THEIR USE FOR THE TREATMENT OF CANCER (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The invention provides complexes of Zn2+ of formulae (la) and (IIa) that are useful for treating cancer, as well as compositions and kits comprising such complexes.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="50.55mm" wi="62.57mm" file="US20180000772A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

SMALL MOLECULE ANTAGONISTS OF DUSP5 AND METHODS OF USE (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The present invention is directed to compounds that specifically target DUSP5 and act as antagonists of that enzyme. Such compounds are useful in the treatment of various conditions including, but not limited to vascular anomalies, cancer, and macular degeneration.</p>
>> Read More

AGENTS FOR USE IN THE DETECTION OF NUCLEASE ACTIVITY (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The present invention relates to the field of diagnostics and, more in particular, to MRI activatable contrast agents and compositions thereof for the detection of nuclease activity, wherein said nuclease activity is caused by microbial infection or by nuclease activity related to cancer, particularly colon cancer or pancreatic cancer. Activatable contrast agents for MRI have been developed, wherein the oligonucleotide is flanked by a paramagnetic and a superparamagnetic agent, and thus providing magnetic quenching. Moreover, the oligonucleotide has regions that confer resistance to mammalian endonucleases and sensitivity to microbial endonucleases. When the activatable contrast agent of the invention is in the presence of microbial nuclease activity or a tumour cell nuclease activity, the oligonucleotide is cleaved, agents are unquenched, and the signal derived from the activated contrast agent is detected by MRI.</p>
>> Read More

BIS(SULFONAMIDE) DERIVATIVES AND THEIR USE AS MPGES INHIBITORS (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The present invention relates to bis(sulfonamide) compounds and pharmaceutically acceptable salts thereof. The present invention also relates to pharmaceutical compositions comprising these compounds and to their use as a medicament for the treatment and/or prevention of a disease, disorder or condition in which modulation of microsomal prostaglandin E synthase-1 activity is beneficial, such as pain, inflammation and cancer.</p>
>> Read More

(THIO, OXO, AND SELENO) SEMICARBAZONE COMPLEXES WITH ZINC AND THEIR USE FOR TREATING CANCER (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The invention provides organic complexes of Zn<sup>2+</sup> of formula (I) that are useful for treating cancer, as well as compositions and kits comprising such complexes, and intermediate monomer compounds that are useful for the preparation of such complexes.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.10mm" wi="64.43mm" file="US20180002279A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

(THIO, OXO, AND SELENO) SEMICARBAZONE DERIVATIVES AND THEIR USE FOR TREATING CANCER (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The invention provides compounds of formula I and II and salts thereof, wherein R<sup>1</sup>, R<sup>2</sup>, Y, R<sup>3</sup>, and R<sup>4 </sup>have any of the meanings described in the specification, as well as compositions comprising such compounds and salts, and methods for treating cancer using such compounds and salts.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="42.59mm" wi="55.96mm" file="US20180002280A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Malate salt of N-(4-phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, including a (L)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide.</p>
>> Read More

PROCESS FOR PREPARING AN ANTI-CANCER AGENT, 1-((4-(4-FLUORO-2-METHYL-1H-INDOL-5-YLOXY)-6-METHOXYQUINOLIN-7-YLOXY)METHYL)CYCLOPROPANAMINE, ITS CRYSTALLINE FORM AND ITS SALTS (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The present invention relates a new process to synthesize 1-((4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxyquinolin-7-yloxy)methyl)cyclopropanamine (AL3818). A stable crystalline form of A13818 has been prepared. Salts and their crystalline forms of AL3818 have been also prepared. Anti-cancer and optometric activities of AL3818 and its salts have been further tested. New process has been outlined in Scheme I.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="197.95mm" wi="75.86mm" file="US20180002311A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

HIGH MOLECULAR WEIGHT POLYSACCHARIDE THAT BINDS AND INHIBITS VIRUS (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">This invention provides a high molecular weight polysaccharide capable of binding to and inhibiting virus and related pharmaceutical formulations and methods of inhibiting viral infectivity and/or pathogenicity, as well as immunogenic compositions. The invention further includes methods of inhibiting the growth of cancer cells and of ameliorating a symptom of aging. Additionally, the invention provides methods of detecting and/or quantifying and/or isolating viruses.</p>
>> Read More

MODIFIED CYTOTOXINS AND THEIR THERAPEUTIC USE (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The present disclosure generally provides compounds useful for treating cancer. In some aspects, the disclosure provides small-molecule cytotoxins that are chemically modified to include one or more moieties that include hydrophobic portions. In some embodiments, the disclosure provides small-molecule cytotoxins that are chemically modified with fatty acid-containing moieties. In some aspects, the disclosure provides compositions, such as pharmaceutical compositions, that include such modified small-molecule cytotoxins and a protein. In some embodiments, the protein is albumin or an albumin mimetic. Further, the disclosure provides various uses of these compounds and compositions.</p>
>> Read More

TARGETED CONJUGATES AND PARTICLES AND FORMULATIONS THEREOF (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">Nanoparticles and microparticles, and pharmaceutical formulations thereof, containing conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to a targeting moiety, such as a somatostatin receptor binding moiety, via a linker have been designed. Such nanoparticles and microparticles can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or infectious diseases.</p>
>> Read More

SUBSTITUTED MONO- AND POLYAZANAPHTHALENE DERIVATIVES AND THEIR USE (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">Disclosed are compounds of formula (I) wherein A is CH or N, B is CR or N; and D is CR; R represents hydrogen, OH or NH<sub>2</sub>; R1 and R2, independently of each other, represent hydrogen, N(R3)<sub>2</sub>, halogen, cyano, nitro, R4-C1-C4alkyl, R4-C1-C4halogenoalkyl, OH, R4-C1-C4alkoxy, R4-C1-C4halogenoalkoxy, SH, R4-C1-C4alkythio, R4-C1-C4halogenoalkylthio; R3 represents, independently at each occurrence, hydrogen, R4-C1-C4alkyl or R4-C1-C4halogenoalkyl; R3a represents, independently at each occurrence, hydrogen or C1-C4 alkyl; R4 represents, independently at each occurrence, hydrogen, halogen, cyano, OH, SH, NH<sub>2</sub>, NH(CH<sub>3</sub>) or N(CH<sub>3</sub>)<sub>2</sub>; X represents a group of formula -E- or -E-F—, wherein E and F are different from each other and represent a group selected from —C(R3a)2-, —(C═O)—, —NR3a- and —O— and F is linked to Y, with the proviso that if X represents -E-F— one of E or F represents —C(R3a)<sub>2</sub>- or —(C═O)—; Y represents a group selected from C1-C6alkyl, mono- or bicyclic C3-C11cycloalkyl, which may be partially unsaturated, mono- or bicyclic 3 to 11-membered heterocycloalkyl, which may be partially unsaturated, a mono- or bicyclic group comprising at least one aryl or heteroaryl cycle, wherein said heterocycloalkyl group and said group comprising at least one heteroaryl cycle comprise one or more heteroatoms selected from nitrogen, oxygen and sulfur and said group Y is either unsubstituted or substituted by one or more substituents and comprises including its substituents one or more than one nitrogen atom having a lone electron pair; and Z represents a mono- or bicyclic group comprising at least one aryl or heteroaryl cycle, said heteroaryl cycle comprising one or more heteroatoms selected from nitrogen, oxygen and sulfur, which aryl or heteroaryl group is unsubstituted or substituted by one or more substituents; including tautomers of said compounds, mixtures of two tautomeric forms of said compounds, and pharmaceutically acceptable salts of said compounds, tautomers thereof or mixtures of two tautomeric forms thereof, preferably with the proviso that Y comprises one or more primary amino group —NH<sub>2</sub>, when X represents —(C═O)— or —(C═O)—NR3a-, wherein R3a represents hydrogen or C1-C4alkyl; which are useful for the treatment of proliferation disorders or diseases, such as cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="55.29mm" file="US20180002321A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

TRICYCLIC HETEROCYCLES AS ANTICANCER AGENTS (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">Tricyclic chemical modulators of FOXO transcription factor proteins are disclosed. The compounds are useful to treat cancer, age-onset proteotoxicity, stress-induced depression, inflammation, and acne. The compounds are of the following and similar genera:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="48.94mm" wi="72.73mm" file="US20180002339A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which Het is an aromatic heterocyclic ring and Y is a point of attachment of various side chains and rings. An example of such a compound is 4-chloro-N-(3-(10,11-dihydro-5H-benzo[b]pyrido[2,3-f]azepin-5-yl)propyl)benzenesulfonamide:</p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="32.43mm" wi="52.41mm" file="US20180002339A1-20180104-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

HETEROCYCLIC INHIBITORS OF MONOCARBOXYLATE TRANSPORTERS (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The invention provides compounds that inhibit monocarboxylate transporters, such as MCT1 and MCT4. Compounds of the invention can be used for treatment of a condition in a patient, wherein the condition is characterized by the heightened activity or by the high prevalence of MCT1 and/or MCT4, such as cancer or type II diabetes.</p>
>> Read More

BUFALIN PHOSPHATE PRODRUGS AND METHODS OF USE THEREOF (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">Bufalin phosphate prodrugs are provided herein, as well as methods for their use as small molecule inhibitors of steroid receptor coactivator (SRC) family proteins. Methods for using bufalin phosphate prodrugs in treating or preventing cancer are also provided herein.</p>
>> Read More

PYRAZOLE DERIVATIVES AS INHIBITORS OF STAT3 (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">Compositions that modulate the activity of signal transducer and activator of transcription-3 (STAT3) activity as well as their methods of use, such as treatment and imaging are provided. Compositions contain small molecules such as substituted pyrazoles and are useful in treatment of diseases related to the activity of STAT3 including, for example, cancer and other diseases.</p>
>> Read More

PROCESSES FOR THE PREPARATION OF A DIARYLTHIOHYDANTOIN COMPOUND (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">Disclosed are processes and intermediates for the preparation of compound (X), which is currently being investigated for the treatment of prostate cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.92mm" wi="70.19mm" file="US20180002309A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

COT MODULATORS AND METHODS OF USE THEREOF (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The present disclosure relates generally to modulators of Cot (cancer Osaka thyroid) and methods of use and manufacture thereof.</p>
>> Read More

BICYCLIC COMPOUND (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">Provided is a bicyclic compound having an acetyl-CoA carboxylase inhibitory action. A compound represented by the formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.02mm" wi="67.90mm" file="US20180002322A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as described in the DESCRIPTION, or a salt thereof has an acetyl-CoA carboxylase inhibitory action, is useful for the prophylaxis or treatment of cancer, inflammatory diseases and the like, and has superior efficacy.</p>
>> Read More

BENZOCYCLOOCTENE-BASED AND INDENE-BASED ANTICANCER AGENTS (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">Benzocyclooctene (fused 6,8 ring system) analogues and corresponding indene (fused 6,5 ring system) analogues function as inhibitors of tubulin polymerization. The compounds are useful as anticancer agents in a new therapeutic approach for cancer treatment utilizing small-molecule inhibitors of tubulin polymerization that also act as vascular disrupting agents (VDAs).</p>
>> Read More

CYCLIC DINUCLEOTIDES USEFUL FOR THE TREATMENT OF INTER ALIA CANCER (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">A compound of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="54.69mm" wi="75.35mm" file="US20180002369A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt and tautomers thereof, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, in the treatment of diseases and conditions in which modulation of STING (Stimulator of Interferon Genes) is beneficial, for example inflammation, allergic and autoimmune diseases, infectious diseases, cancer, pre-cancerous syndromes and as vaccine adjuvants</p>
>> Read More

FAS AND DRs ARE NOVEL MOLECULAR TARGETS OF SENESCENT CELLS (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The present invention relates to modulators of FAS and DRs and their method of use in the treatment and prevention of diseases and pathologies related to accumulation of senescent cells during aging, such as cancer, chronic obstructive pulmonary disease (COPD), osteoarthritis, atherosclerosis, neurodegenerative diseases, diabetes, and many others. The present invention also relates to pharmaceutical compositions containing these compounds as well as various uses thereof.</p>
>> Read More

ANTIBODIES AGAINST GLUCOCORTICOID-INDUCED TUMOR NECROSIS FACTOR RECEPTOR (GITR) AND USES THEREOF (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">Provided herein are antibodies, or antigen binding portions thereof, that bind to glucocorticoid-inducible TNF receptor (GITR). Also provided are uses of these proteins in therapeutic applications, such as in the treatment of cancer. Further provided are cells that produce the antibodies, polynucleotides encoding the heavy and/or light chain variable region of the antibodies, and vectors comprising the polynucleotides encoding the heavy and/or light chain variable region of the antibodies.</p>
>> Read More

ANTI-MERTK AGONISTIC ANTIBODIES AND USES THEREOF (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The present disclosure provides antibodies that specifically bind to Mer Tyrosine Kinase (MERTK) (e.g., human MERTK, or both human and mouse MERTK) and compositions comprising such antibodies, wherein said antibody agonizes MERTK signaling on endothelial cells. The present disclosure also provides methods for treating cancer, by administering an antibody that specifically binds to MERTK and agonizes MERTK signaling on endothelial cells.</p>
>> Read More

HYDRAZONE DERIVATIVES FOR THE TREATMENT OF CANCER (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The invention provides compounds of formula (I): and salts thereof wherein ring A, R<sup>2</sup>, HET, X, n, and R<sup>3 </sup>have any of the meanings described in the specification, as well as compositions comprising such compounds and salts, and methods for treating cancer using such compounds and salts.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.89mm" wi="61.72mm" file="US20180000806A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

CYCLOPROPYLAMINES AS LSD1 INHIBITORS (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">This invention relates to the use of cyclopropylamine derivatives for the modulation, notably the inhibition of the activity of Lysine-specific demethylase 1 (LSD1). Suitably, the present invention relates to the use of cyclopropylamines in the treatment of cancer.</p>
>> Read More

KINASE INHIBITOR AND USE THEREOF (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The invention relates to a CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers; a pharmaceutical formulation, pharmaceutical composition and kit comprising said CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers, and use of said CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers. For example, the compounds of the invention are useful for reducing or inhibiting the activity of CDK4/6 kinase in a cell, and/or treating and/or preventing a cancer-related disease mediated by CDK4/6 kinase.</p>
>> Read More

PHOSPHOLIPID COMPOSITIONS (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">Compositions involving a modified egg yolk extract for use as an effective anti-cancer agent are described. The modified egg yolk extract involves specific fractions of phosphatidylcholines and sphingomyelins modified and produced from a chemical synthesis applied to the extract that produce a beneficial effect on the inhibition of cancerous cell growth. Methods of administering these compositions are also described.</p>
>> Read More

Virus Vectors Expressing Multiple Epitopes of Tumor Associated Antigens For Inducing Antitumor Immunity (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">Provided are polynucleotides and viral vectors, particularly, alphavirus vectors such as Sindbis viral vectors, which encode multiple, e.g., two or more, epitopes of at least one tumor associated antigen in which each epitope is separated by a processing or enzyme cleavage site. The multiple epitopes of the two or more tumor associated antigens encoded by the described polynucleotides and viral vectors may be the same or different. Methods of treating mammalian subjects having a cancer or tumor expressing the tumor associated antigen epitopes are provided, in which the viral vectors encoding the multiple epitopes, as well as other immunostimulatory or immunomodulatory components, generate an anti-cancer or anti-tumor immune response in which high levels of effector T cells increase the survivability of tumored mammalian subjects and result in epitope spreading, thus providing a further enhancement of the immune response.</p>
>> Read More

TRICYCLIC HETEROCYCLES AS BET PROTEIN INHIBITORS (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The present invention relates to tricyclic heterocycles which are inhibitors of BET proteins such as BRD2, BRD3, BRD4, and BRD-t and are useful in the treatment of diseases such as cancer.</p>
>> Read More

PHOSPHOLIPID COMPOSITIONS (Fri, 05 Jan 2018)
Compositions involving a modified egg yolk extract for use as an effective anti-cancer agent are described. The modified egg yolk extract involves specific fractions of phosphatidylcholines and sphingomyelins modified and produced from a chemical synthesis applied to the extract that produce a beneficial effect on the inhibition of cancerous cell growth. Methods of administering these compositions are also described.
>> Read More

COMBINATION OF ERK1/2 INHIBITOR COMPOUND WITH GEMCITABINE OR WITH GEMCITABINE AND NAB-PACLITAXEL FOR USE IN TREATMENT OF PANCREATIC CANCER (Fri, 05 Jan 2018)
The present invention provides a combination of an ERK1/2 inhibitor compound, 6,6-dimethyl-2-{2-[(1-methyl-1H-pyrazol-5-yl)amino]pyrimidin-4-yl}-5-[2-(morpholin- 4-yl) ethyl]-5,6-dihydro-4H-thieno[2,3-c]pyrrol-4-one, or a pharmaceutically acceptable salt thereof, with gemcitabine, or a pharmaceutically acceptable salt thereof, preferably hydrochloride, or with gemcitabine, or a pharmaceutically acceptable salt thereof, preferably hydrochloride, and nab-paclitaxel, and to methods of using the combination to treat certain disorders, such as pancreatic cancer, including pancreatic ductal adenocarcinoma (PDAC).
>> Read More

4,6-DIAMINOQUINAZOLINES AS COT MODULATORS AND METHODS OF USE THEREOF (Fri, 05 Jan 2018)
The invention relates to 4,6-diaminoquinazoline derivatives of formula I which are modulators of the Cot (cancer Osaka thyroid) kinase, also known as MAP3K8, EST or Tlp-2, and their use for treating e.g. cancer, diabetes and inflammatory diseases.
>> Read More

COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CANCER (Fri, 05 Jan 2018)
The present disclosure provides compounds, pharmaceutical compositions, and methods for the treatment of cancer and fibrosis. The disclosed pharmaceutical compositions may include one or more pyrazolyl-containing compounds, or a derivative thereof.
>> Read More

RENAL CLEARABLE ORGANIC NANOCARRIERS (Fri, 05 Jan 2018)
Disclosed herein are nanocarriers that include one or more cyclodextrin moieties conjugated to a polymer. The cyclodextrin moieties can complex therapeutic (e.g., anticancer) agents, and can be used to treat diseases such as cancer.
>> Read More

HISTONE DEACETYLASE AND HISTONE METHYLTRANSFERASE INHIBITORS AND METHODS OF MAKING AND USE OF THE SAME (Fri, 05 Jan 2018)
The compounds of formula (I) are dual inhibitors of the enzymes histone deacetylases (HDACs) and histone methyltransferase G9a, both of which are key posttranslational enzymes in cancer development.
>> Read More

1 H-PYRAZOL-1 -YL-THIAZOLES AS INHIBITORS OF LACTATE DEHYDROGENASE AND METHODS OF USE THEREOF (Fri, 05 Jan 2018)
The disclosure provides a compound of the formula (II) and pharmaceutically acceptable salts thereof. The variables, e.g. n, R, R3, R10, X, Y, and Z are defined herein. These compounds act as lactate dehydrogenase inhibitors and are useful for treating cancer and fibrosis. The compounds may be particularly useful for treating forms of cancer in which a metabolic switch from oxidative phosphorylation to glycolysis has occurred. The disclosure also provides pharmaceutical compositions containing a compound of this formula and method for treating patients having cancer, fibrosis, or other conditions in which a metabolic switch from oxidative phosphorylation to glycolysis has occurred.
>> Read More

PYRIMIDINE-BASED COMPOUNDS FOR THE TREATMENT OF CANCER (Fri, 05 Jan 2018)
This invention is in the area of pyrimidine-based compounds for the treatment of disorders involving abnormal cellular proliferation, including but not limited to tumors and cancers.
>> Read More

SYNTHESIS OF NEW METHYLUMBELLIFERONE PRODRUGS AND THEIR INCORPORATION INTO LIPID-BASED DRUG DELIVERY FORMULATIONS (Fri, 05 Jan 2018)
Lipophilic prodrugs of 4-methylumbelliferone are incorporated into lipid based drug delivery systems (e.g., emulsions, micelles, liposomes and lipid particles). The formulations protect 4-methylumbelliferone from first pass hepatic metabolism to 4-MUG. Exemplary formulations are oral and parenteral formulations. Methods of treating proliferative diseases, e.g., cancer by administering the formulation to a subject in need thereof are provided.
>> Read More

COMPOSITIONS, ASSAYS, AND METHODS FOR DIRECT MODULATION OF FATTY ACID METABOLISM (Fri, 05 Jan 2018)
This disclosure relates to the surprising and unexpected finding that the well-known cancer protein, Myeloid Cell Leukemia-1 (MCL-1), binds to and modulates the enzymatic activity of Very Long Chain Acyl CoA Dehydrogenase (VLCAD), thereby regulating fatty acid β-oxidation. This finding is employed in compositions and methods of treating cancer, metabolic diseases, or other conditions characterized by excessive fatty acid β-oxidation by blocking or reducing the energy production of cells (e.g., cancer) through inhibiting the MCL-1/VLCAD interaction and/or directly inhibiting VLCAD enzymatic activity. In addition, the disclosure features methods for identifying such agents that inhibit the interaction between MCL-1 and VLCAD or that inhibit VLCAD enzymatic activity.
>> Read More

HETEROAROMATIC DERIVATIVES AS NIK INHIBITORS (Fri, 05 Jan 2018)
The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-κB-inducing kinase (NIK - also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.
>> Read More

CYANOINDOLINE DERIVATIVES AS NIK INHIBITORS (Fri, 05 Jan 2018)
Fused aromatic bicyclic substituted 5-(2-amino-4-pyrimidinyl)- cyanoindoline derivatives (I) useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-KB-inducing kinase (NIK - also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.
>> Read More

MITOCHONDRIAL INHIBITORS FOR THE TREATMENT OF PROLIFERATION DISORDERS (Fri, 05 Jan 2018)
The invention provides compounds of formula I or pharmaceutically acceptable salt, solvate or hydrate thereof (I) wherein ring A represents group A-I or A- II (A-I, A-II) A1, A2, A3, A4 represent independently C(R4aa) or N, wherein no more than one of A1, A2, A3, and A4 represents N; A5 represents C(R4b) or N; B1, B2, B3 and B4 represent independently C(R3) or N, wherein no more than two of B1, B2, B3 and B4 represent N; n is 1 or 2; and R1, R2, R3, R4a and R4aa and R4b are as defined in the claims, as well as methods of using the compounds to treat proliferation diseases, in particular cancer.
>> Read More

CLEAVABLE POLYMER DRUG CONJUGATES (Fri, 05 Jan 2018)
This invention relates to polymer drug conjugates comprising a (meth)acrylate based polymer backbone with at least two types of side chains wherein one of the side chains is a PEG chain and the other side chain comprises at least one therapeutic agent covalently bonded to a cleavable linker, methods of preparing said polymer-drug conjugates and their use for treatment of diseases such as cancer.
>> Read More

HYODEOXYCHOLIC ACID DERIVATIVES AND USE THEREOF (Fri, 05 Jan 2018)
The present invention concerns compounds having formula (I) and compositions thereof with a pharmacologically acceptable excipient and uses thereof as a medicament, in particular for the treatment and/or prevention of a disorder selected from the group consisting of: gastrointestinal disorders, liver diseases, cardiovascular and vascular diseases, pulmonary and metabolic diseases, infectious diseases, cancer, renal disorders, inflammatory disorders comprising immune mediated disorders, and neurological disorders.
>> Read More

SUBSTITUTED THIENOPYRROLOPYRIMIDINE RIBONUCLEOSIDES FOR THERAPEUTIC USE (Fri, 05 Jan 2018)
Substituted thienopyrrolopyrimidine ribonucleosides for therapeutic use The invention provides a new group of substituted thienopyrrolopyrimidine ribonucleosides of general formula I, wherein R is defined in the claims. The compounds of this invention show strong cytostatic and cytotoxic activities preferably against cancer cell lines of broad spectrum of diseases including tumors of various histogenetic origin.
>> Read More

Use of inhibitors of Bruton's tyrosine kinase (Btk) (Fri, 05 Jan 2018)
Methods are provided for treating a hematologic cancer comprising administering an anticancer agent to a subject identified as having an increased mobilization of a subpopulation of lymphocytes from a malignancy following administration of an irreversible Btk inhibitor. Methods also are provided for identification of subjects for treatment and the analysis of cells mobilized from a hematologic malignancy following administration of an irreversible Btk inhibitor.
>> Read More

Specific binding proteins and uses thereof (Fri, 05 Jan 2018)
The present invention relates to specific binding members, particularly antibodies and fragments thereof, which bind to amplified epidermal growth factor receptor (EGFR) and to the de2-7 EGFR truncation of the EGFR. In particular, the epitope recognized by the specific binding members, particularly antibodies and fragments thereof, is enhanced or evident upon aberrant post-translational modification. These specific binding members are useful in the diagnosis and treatment of cancer. The binding members of the present invention may also be used in therapy in combination with chemotherapeutics or anti-cancer agents and/or with other antibodies or fragments thereof.
>> Read More

HSP90 combination therapy (Fri, 05 Jan 2018)
This disclosure concerns a method for selecting an inhibitor of a cancer-implicated pathway or of a component thereof for coadministration with an inhibitor of HSP90 the method comprising: (a) contacting a sample containing cancer cells from a subject with an inhibitor of HSP90 under conditions such that one or more cancer pathway components present in the sample bind to the HSP90 inhibitor
>> Read More

IAP BIR DOMAIN BINDING COMPOUNDS (Thu, 04 Jan 2018)
A compound of Formula 1: or salt thereof, as well as methods of making compounds of Formula 1, methods of using compounds of Formula 1 to treat proliferative disorders such as cancer, and related compounds, composition, and methods.
>> Read More

PYRIDINONE COMPOUND AND USE THEREOF (Thu, 04 Jan 2018)
The present invention provides a compound capable of being used as an active ingredient of an anti-cancer agent. To provide an anti-cancer agent with few side effects, an object of the present invention is to provide a compound capable of selectively inhibiting the target, i.e., DOCK1, or a salt thereof. The pyridinone compound of the present invention is represented by Formula (1): wherein R 1 and R 2 are the same or different, and each represents C 1-6 alkyl; and R 3 is a group represented by, for example, Formula (3) below: wherein R 5 in the group represented by Formula (3) is hydrogen.
>> Read More

BIOMARKERS AND METHODS OF TREATMENT (Thu, 04 Jan 2018)
The present invention concerns cancer biomarkers. In particular, the invention concerns c-met as biomarkers for patient selection and patient prognosis in cancer, as well as methods of therapeutic treatment, articles of manufacture and methods for making them, diagnostic kits, methods of detection and methods of advertising related thereto.
>> Read More

Substituted naphthyridinyl hydrazines as anti-liver cancer agents (Wed, 03 Jan 2018)
<p id="p-0001" num="0000">The substituted naphthyridinyl hydrazine compounds as anti-liver cancer agents are anti-liver cancer agents that inhibit proliferative pathways of cancer cells, thereby exhibiting potent in vitro and in vivo anticancer activity. The compounds have the formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.01mm" wi="38.02mm" file="US09855255-20180102-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein R<sub>1 </sub>and R<sub>2 </sub>each are selected independently from hydrogen, mercapto, and C<sub>1</sub>-C<sub>5</sub>-alkyl, preferably methyl, ethyl, propyl, isopropyl or halogen; R<sub>3 </sub>and R<sub>4 </sub>each are selected independently from hydrogen, alkyl or halogen; and R<sub>5 </sub>is selected from substituted or unsubstituted aryl, more preferably from substituted phenyl, naphthyl, and substituted or unsubstituted heteroaryl, more preferably from furyl, pyrrolyl, thienyl, imidazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, benzothiazolyl, oxadiazolyl or sugar moities. These agents exert their action through topoisomerase II inhibition. </p>
>> Read More

MONOHYDROXYPHENYL METABOLITE URINE DETECTION REAGENT AND PREPARATION METHOD THEREOF (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">A reagent for detection of urine monophenolic metabolites and a method for preparing the reagent are disclosed, in which the monophenolic metabolites, for example, tyrosine, p-hydroxyphenyl alanine, tryptophan and 5-hydroxyindoleacetic acid can serve as tumor markers. The reagent for detection of urine monophenolic metabolites is an aqueous solution containing nitric acid, sulfuric acid, mercuric sulfate, mercurous nitrate, nickel nitrate, phosphomolybdic acid and cobalt sulfate. The preparation method includes preparation of solutions A, B, C, D and E, and mixing. The subject matter allows easy availability of raw materials, low cost, a simple preparation process, obtainment of reagents with stable performance which offer the advantages including high versatility, high sensitivity and good specificity when used in cancer detection, a simple detection process, a short detection cycle and easy determination, and is particularly suitable for large population screening, assistance in clinical cancer diagnosis and dynamic follow-up.</p>
>> Read More

IMIDAZOPYRAZINES AS LSD1 INHIBITORS (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The present invention is directed to imidazo[1,2-a]pyrazine derivatives of Formula I, or a pharmaceutically acceptable salt thereof, which are LSD1 inhibitors useful in the treatment of diseases such as cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.07mm" wi="52.49mm" file="US20170369497A1-20171228-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">This invention is directed to pyrrole, pyrazole, imidazole, triazole, and morpholine based selective androgen receptor degrader (SARD) compounds including heterocyclic anilide rings and their synthetic precursors, R-isomers, and non-hydroxylated and/or non-chiral propanamides, and pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.</p>
>> Read More

Diagnostics and Therapeutics for Diseases Associated With G-Protein Coupled Receptor AdipoR2 (AdipoR2) (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The invention provides human AdipoR2 which is associated with the cardiovascular diseases, dermatological diseases, gastroenterological diseases, cancer, hematological diseases, respiratory diseases, inflammation, neurological diseases, urological diseases. The invention also provides assays for the identification of compounds useful in the treatment or prevention of cardiovascular diseases, dermatological diseases, gastroenterological diseases, cancer, hematological diseases, respiratory diseases, inflammation, neurological diseases, urological diseases. The invention also features compounds which bind to and/or activate or inhibit the activity of AdipoR2 as well as pharmaceutical compositions comprising such compounds.</p>
>> Read More

TREATMENT OR PROPHYLAXIS OF PROLIFERATIVE CONDITIONS (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The invention relates to novel compounds for use in the treatment or prophylaxis of cancers and other proliferative conditions that are for example characterized by cells that express cytochromne P450 1B1 (CYP1B1) and allelic variants thereof. The invention also provides pharmaceutical compositions comprising one or more such compounds for use in medical therapy, for example in the treatment of prophylaxis of cancers or other proliferative conditions, as well as methods for treating cancers or other conditions in human or non-human animal patients. The invention also provides methods for identifying novel compounds for use in the treatment of prophylaxis of cancers and other proliferative conditions that are for example characterized by cells that express CYP1 B1 and allelic variants thereof. The invention also provides a method for determining the efficacy of a compound of the invention in treating cancer.</p>
>> Read More

BI-FUNCTIONAL ALLOSTERIC PROTEIN-DRUG MOLECULES FOR TARGETED THERAPY (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">Disclosed herein, is a bi-functional allosteric protein-drug molecule comprising a targeting moiety, one or more biological binding domains, and one or more therapeutic agents, wherein the therapeutic agent is allosterically bound to the biological binding domain. Also described herein, are methods of incorporating a bi-functional allosteric protein-drug molecule comprising a targeting moiety, one or more biological binding domains that captures the therapeutic agent without the formation of a chemical bond, and one or more therapeutic agents; physiologically acceptable compositions including them; and methods of administering the bi-functional allosteric protein-drug molecule to patients for the treatment of cancer.</p>
>> Read More

CANCER IMAGING AGENT (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The present disclosure relates to imaging agent formulations, methods for preparing imaging agent formulations and methods for using the same. The present disclosure also relates to kits for imaging agent formulations.</p>
>> Read More

TAK1 Kinase Inhibitors, Compositions, and Uses Related Thereto (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The disclosure relates to TAK1 inhibitors, compositions, and uses related thereto. In certain embodiments, the disclosure relates to compounds of formula I, pharmaceutical compositions having a compound of formula I, and methods of treating or preventing cancer by administering an effective amount of a pharmaceutical composition having a compound of formula I to a subject in need thereof.</p>
>> Read More

SELECTIVE HISTONE DEACTYLASE 6 INHIBITORS (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">Disclosed are selective histone deactylase inhibitors (HDACi) that having Formula I. Methods of making and using these inhibitors for the treatment of cancer, in particular melanoma are also disclosed.</p>
>> Read More

Cyclic Compounds and Uses Thereof (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The invention generally relates to substituted benzothiophenyl, substituted benzothiazolyl, substituted indolyl and substituted benzoimidazolyl compounds and, more particularly, to a compound represented by Structural Formula I: or a pharmaceutically acceptable salt thereof, wherein the variables are as defined and described herein. The invention also includes the synthesis and use of a compound of Structural Formula I, or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment of a disease or disorder selected from cancer (e.g., lymphoma, such as mantle cell lymphoma), a neurodegenerative disease, inflammatory diseases or an autoimmune system disease (e.g., a T-Cell mediated autoimmune disesase).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.86mm" wi="64.43mm" file="US20170369470A1-20171228-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

COMPOUNDS, COMPOSITIONS AND METHODS OF USE (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">Herein, compounds, compositions and methods for modulating inclusion formation and stress granules in cells related to the onset of neurodegenerative diseases, musculoskeletal diseases, cancer, ophthalmological diseases, and viral infections are described.</p>
>> Read More

TRIAZOLOPYRIDINES AND TRIAZOLOPYRAZINES AS LSD1 INHIBITORS (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The present invention is directed to [1,2,4]triazolo[1,5-a]pyridine and [1,2,4]triazolo[1,5-a]pyrazine derivatives of Formula I, or a pharmaceutically acceptable salt thereof, which are LSD1 inhibitors useful in the treatment of diseases such as cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.16mm" wi="52.41mm" file="US20170369488A1-20171228-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

IMIDAZOPYRIDINES AND IMIDAZOPYRAZINES AS LSD1 INHIBITORS (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The present invention is directed to imidazo[1,5-a]pyridine and imidazo[1,5-a]pyrazine derivatives of Formula I, or a pharmaceutically acceptable salt thereof, which are LSD1 inhibitors useful in the treatment of diseases such as cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.72mm" wi="54.78mm" file="US20170369487A1-20171228-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

DEUTERATED COMPOUNDS FOR TREATING CANCER AND RELATED DISEASES AND CONDITIONS, AND COMPOSITIONS AND METHODS THEREOF (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The invention provides novel chemical compounds useful for treating cancer or a related disease or disorder thereof, and pharmaceutical composition and methods of preparation and use thereof.</p>
>> Read More

PHARMACEUTICAL COMPOSITIONS COMPRISING POH DERIVATIVES (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The present invention provides for a derivative of monoterpene or sesquiterpene, such as a perillyl alcohol derivative. For example, the perillyl alcohol derivative may be a perillyl alcohol carbamate. The perillyl alcohol derivative may be perillyl alcohol conjugated with a therapeutic agent such as a chemotherapeutic agent. The present invention also provides for a method of treating a disease such as cancer, comprising the step of delivering to a patient a therapeutically effective amount of a derivative of monoterpene (or sesquiterpene). The route of administration may vary, and can include, inhalation, intranasal, oral, transdermal, intravenous, subcutaneous or intramuscular injection.</p>
>> Read More

INHIBITORS OF HISTONE DEMETHYLASES (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">Compounds of the form in which Q is selected from —COOH—CH═NR<sup>12</sup>, —W, —CH<sub>2</sub>NHR<sup>13</sup>, —CH=0 and —CH(OR<sup>17</sup>)<sub>2 </sub>capable of modulating the activity of histone demethylases (HDMEs), which are useful for prevention and/or treatment of diseases in which genomic dysregulation is involved in the pathogenesis, such as e.g. cancer and formulations and methods of use of such compounds.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.30mm" wi="31.41mm" file="US20170369444A1-20171228-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

KINASE INHIBITORS FOR THE TREATMENT OF DISEASE (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The invention relates to compounds and their use in the treatment of disease. Novel irreversible inhibitors of wild-type and mutant forms of EGFR, FGFR, ALK, ROS, JAK, BTK, BLK, ITK, TEC, and/or TXK and their use for the treatment of cell proliferation disorders are described.</p>
>> Read More

Bicyclic PKM2 Activators (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">Compounds and compositions comprising compounds that activate pyruvate kinase M2 (PKM2) are described herein. Also described herein are methods of using the compounds that activate PKM2 in the treatment of cancer.</p>
>> Read More

CK2 INHIBITORS, COMPOSITIONS AND METHODS THEREOF (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula (I), or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.71mm" wi="55.29mm" file="US20170369489A1-20171228-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">For Formula (I) compounds R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, Ar and Z are as defined in the specification. The inventive Formula (I) compounds are inhibitors of CK2 and find utility in any number of therapeutic applications, including but not limited to treatment of proliferative disorders such as cancer, inflammation and immunological disorders.</p>
>> Read More

CONFORMATIONALLY RESTRICTED 4-SUBSTITUTED-2,6-DIMETHYLFURO[2,3-d]PYRIMIDINES AS ANTI-TUMOR AGENTS (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The present invention provides conformationally restricted 4-substituted 2,6-dimethylfuro[2,3-d]pyrimidine compounds and pharmaceutical compositions comprising these compounds. Preferably, the compounds exhibit dual inhibition of microtubule assembly and receptor tyrosine kinases. Methods of treating cancer comprising administering a therapeutically effective amount of at least one conformationally restricted 4-substituted 2,6-dimethylfuro[2,3-d]pyrimidine compound to a patient is disclosed.</p>
>> Read More

DOUBLE TARGETED CONSTRUCTS TO AFFECT TUMOR KILL (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The present technology is directed to compounds, compositions, medicaments, and methods related to the treatment of cancers expressing PSMA. The compounds are of Formulas I & II</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="85.94mm" wi="74.42mm" file="US20170368005A1-20171228-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salts thereof. The present technology is especially well-suited for use in treating prostate cancer.</p>
>> Read More

MACROCYCLIC INHIBITORS OF THE PD-1/PD-L1 AND CD80(B7-1)/PD-L1 PROTEIN/PROTEIN INTERACTIONS (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The present disclosure provides novel macrocyclic peptides which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.</p>
>> Read More

3-HETEROCYCLYL SUBSTITUTED 5-TRIFLUOROMETHYL OXADIAZOLES AS HISTONE DEACETYLASE 6 (HDAC6) INHIBITORS (Fri, 29 Dec 2017)
The present invention is directed to substituted 5-trifluoromethyl oxadiazole compounds of generic formula (I) (I) or a pharmaceutically acceptable salt thereof. In particular, the invention is directed to a class of aryl and heteroaryl substituted 5-trifluoromethyl oxadiazole compounds of formula I which may be useful as HDAC6 inhibitors for treating cellular proliferative diseases, including cancer, neurodegenerative diseases, such as schizophrenia and stroke, as well as other diseases.
>> Read More

3-ARYL AND HETEROARYL SUBSTITUTED 5-TRIFLUOROMETHYL OXADIAZOLES AS HISTONE DEACETYLASE 6 (HDAC6) INHIBITORS (Fri, 29 Dec 2017)
The present invention is directed to substituted 5-trifluoromethyl oxadiazole compounds of generic formula (I) or a pharmaceutically acceptable salt thereof. In particular, the invention is directed to a class of aryl and heteroaryl substituted 5-trifluoromethyl oxadiazole compounds of formula I which may be useful as HDAC6 inhibitors for treating cellular proliferative diseases, including cancer, neurodegenerative diseases, such as schizophrenia and stroke, as well as other diseases.
>> Read More

3- HETEROARYL SUBSTITUTED 5-TRIFLUOROMETHYL OXADIAZOLES AS HISTONE DEACETYLASE 6 (HDAC6) INHIBITORS (Fri, 29 Dec 2017)
The present invention is directed to substituted 5-trifluoromethyl oxadiazole compounds of generic formula (I) (I) or a pharmaceutically acceptable salt thereof. In particular, the invention is directed to a class of heteroaryl substituted 5-trifluoromethyl oxadiazole compounds of formula I which may be useful as HDAC6 inhibitors for treating cellular proliferative diseases, including cancer, neurodegenerative diseases, such as schizophrenia and stroke, as well as other diseases.
>> Read More

CRYSTALLINE SOLID FORMS OF A BET INHIBITOR (Fri, 29 Dec 2017)
The present application relates to crystalline solid forms of an inhibitor of BET proteins such as BRD2, BRD3, BRD4, and BRD-t, including methods of preparation thereof, and intermediates in the preparation thereof, where the compound is useful in the treatment of diseases such as cancer.
>> Read More

SMALL MOLECULE INHIBITORS OF ALDH AND USES THEREOF (Fri, 29 Dec 2017)
This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a thiopyrimidinone structure which function as inhibitors of ALDH protein, and their use as therapeutics for the treatment of cancer and other diseases.
>> Read More

SUBSTITUTED ISOSELENAZOLONE ANTI-INFLAMMATORY, ANTI-CANCER, CYTOPROTECTIVE, NEUROPROTECTIVE, AND ANTI-OXIDANT AGENTS (Fri, 29 Dec 2017)
Compounds, compositions, and methods for the treatment of infections, inflammation, cancers, tinnitus, Meniere's disease, hearing loss, or bipolar disorder, or for providing cytoprotection against Clostridium difficile toxins, are disclosed.
>> Read More

ALDOSE REDUCTASE INHIBITORS AND METHODS OF USE THEREOF (Fri, 29 Dec 2017)
The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for promoting healthy aging of skin, the treatment of skin disorders, the treatment of cardiovascular disorders, the treatment of renal disorders, the treatment of angiogenesis disorders, such as cancer, treatment of tissue damage, such as non-cardiac tissue damage, the treatment of evolving myocardial infarction, the treatment of ischemic injury, and the treatment of various other disorders, such as complications arising from diabetes with the compounds and compositions of the invention. Other disorders can include, but are not limited to, atherosclerosis, coronary artery disease, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, diabetic cardiomyopathy, infections of the skin, peripheral vascular disease, stroke, asthma, and the like.
>> Read More

THIAZOLE DERIVATIVES USEFUL AS MUTANT IDH1 INHIBITORS FOR TREATING CANCER (Fri, 29 Dec 2017)
A compound of Formula II or a pharmaceutically acceptable salt thereof, wherein CyN is a cyclic amine group bound via a nitrogen atom; X is C or N; R1 and R2 are each independently a halogen, CN, CF3, CHF2, CH2F, a C1-C10alkyl group, a C1-C10alkoxy group, a di(C1-C5alkyl)amino; m and n are each independently 1, 2, or 3, and represents either a single bond or a double bond, wherein the racemic mixture of 3-(4-(4-chlorophenyl)thiazol-2-yl)-1-(2-ethyl-5-methoxyphenyl)-6-(2-methylprop-1-en-1-yl)-5-(piperazine-1-carbonyl)pyridin-2(1H)-one atropisomers is excluded.
>> Read More

NON-CATALYTIC SUBSTRATE-SELECTIVE P38α-SPECIFIC MAPK INHIBITORS WITH ENDOTHELIAL-STABILIZING AND ANTI-INFLAMMATORY ACTIVITY, AND METHODS OF USE THEREOF (Fri, 29 Dec 2017)
Compounds that inhibit p38α MAPK protein, and methods of using the same, are provided for treating or preventing diseases such as cancer or inflammatory diseases.
>> Read More

DOUBLE TARGETED CONSTRUCTS TO AFFECT TUMOR KILL (Fri, 29 Dec 2017)
The present technology is directed to compounds, compositions, medicaments, and methods related to the treatment of cancers expressing PSMA. The compounds are of Formulas I & II, or pharmaceutically acceptable salts thereof. The present technology is especially well-suited for use in treating prostate cancer.
>> Read More

HETEROCYCLIC COMPOUNDS AS PI3K-γ INHIBITORS (Fri, 29 Dec 2017)
This application relates to compounds of Formula (I) or pharmaceutically acceptable salts or stereoisomers thereof, which are inhibitors of PI3K-γ which are useful for the treatment of disorders such as autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.
>> Read More

DEGRADATION OF TRIPARTITE MOTIF-CONTAINING PROTEIN 24 (TRIM24) BY CONJUGATION OF TRIM24 INHIBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE (Fri, 29 Dec 2017)
The present application provides bifunctional compounds of Formula Ia or Ib: (Ia), or Targeting Ligand (Ib), Targeting Ligand or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for tripartite motif-containing 24 (TRIM24). The present application also relates to methods for the targeted degradation of TRIM24 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to TRIM24 which can be utilized in the treatment of disorders modulated by TRIM24.
>> Read More

RHENIUM COMPLEXES AND METHODS OF USE FOR TREATING CANCER (Fri, 29 Dec 2017)
A composition comprising the following structure: (formula I) wherein Re represents a rhenium ion having a +1 charge; (formula II) represents an uncharged bidentate bicyclic ligand bonded to the rhenium (Re) by two ring nitrogen (N) atoms; and L is a neutral ligand independently selected from CO and neutral phosphine molecules, wherein at least one of the L groups is a CO molecule; and X- represents a non-coordinating monovalent anion; wherein (formula II) is unsubstituted or substituted on any of its two rings, and said neutral phosphine molecule may or may not contain a phosphorus atom as a ring phosphorus atom; provided that, if (formula II) is unsubstituted, then one or two of said L groups are selected from said neutral phosphine molecules, with the provision that at least one of the neutral phosphine molecules has a phosphorus atom as a ring phosphorus atom. Methods for treating cancer by administering the above complex are also disclosed.
>> Read More

CK2 INHIBITORS, COMPOSITIONS AND METHODS THEREOF (Fri, 29 Dec 2017)
The present invention provides synthesis, pharmaceutically acceptable formulations and uses of compounds in accordance with Formula (I), or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof. (formula I) For Formula (I) compounds R1, R2, R3, Ar and Z are as defined in the specification. The inventive Formula (I) compounds are inhibitors of CK2 and find utility in any number of therapeutic applications, including but not limited to treatment of proliferative disorders such as cancer, inflammation and immunological disorders.
>> Read More

DEGRADATION OF BROMODOMAIN-CONTAINING PROTEIN 9 (BRD9) BY CONJUGATION OF BRD9 INHIBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE (Fri, 29 Dec 2017)
The present application provides bifunctional compounds of Formula (I): or an enantiomer, diastereomer, or stereoisomer thereof, or pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, which act as protein degradation inducing moieties for bromodomain-containing protein 9 (BRD9). The present application also provides methods for the targeted degradation of BRD9 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to BRD9 which can be utilized in the treatment of disorders modulated by BRD9.
>> Read More

PHTHALAZINE DERIVATIVES AS INHIBITORS OF PARP1, PARP2 AND/OR TUBULIN USEFUL FOR THE TREATMENT OF CANCER (Fri, 29 Dec 2017)
The application relates to phthalazine derivatives of formula (I) which are inhibitors of PARP1, PARP2 and/or tubulin and thus useful for the treatment of cancer. Also disclosed are pharmaceutical formulations containing such compounds, as well as combinations of these compounds with at least one additional therapeutic agent.
>> Read More

IMIDAZOPYRIMIDINE COMPOUNDS USEFUL FOR THE TREATMENT OF CANCER (Fri, 29 Dec 2017)
A compound of Formula (IA), or a pharmaceutically acceptable salt thereof, is provided that has been shown to be useful for treating a PRC2-mediated disease or disorder: wherein A, R3, R4, R6, and R7 are as defined herein.
>> Read More

HYBRID MUCO-ADHESIVE DELIVERY SYSTEMS AND USE THEREOF (Fri, 29 Dec 2017)
A composition and method for the administration of therapeutic and/or diagnostic agents is provided. Specifically, a hybrid system, composed of polymer that harbors drug-loaded lipid nanoparticles, and use thereof for the administration of active agents e.g., anti-cancer agents, is provided.
>> Read More

MECHANISTIC TARGET OF RAPAMYCIN SIGNALING PATHWAY INHIBITORS AND THERAPEUTIC APPLICATIONS THEREOF (Fri, 29 Dec 2017)
Selective mTOR inhibitors of formulas (I)-(III), processes for their preparation, pharmaceutical compositions containing them, and their use in the treatment of diseases and disorders, arising from abnormal cell growth, functions, or behaviors mediated by an mTOR kinase and/or one or more PI3K enzyme, are provided. Such diseases and disorder include cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine function disorders and neurological disorders.
>> Read More

SUBSTITUTED PYRROLO [2, 3-D] PYRIDAZIN-4-ONES AND PYRAZOLO [3, 4-D] PYRIDAZIN-4-ONES AS PROTEIN KINASE INHIBITORS (Fri, 29 Dec 2017)
Provided are certain compounds or pharmaceutically acceptable salts thereof which can inhibit kinase activity of Bruton's tyrosine kinase (BTK) and may be useful for the treatment of diseases like cancer, immunological disease and inflammation.
>> Read More

N-(SUBSTITUTED-PHENYL)-SULFONAMIDE DERIVATIVES AS KINASE INHIBITORS (Fri, 29 Dec 2017)
The invention relates to N-(substituted-phenyl)-sulfonamide compounds, which are extremely useful as inhibitors of protein kinases (e.g. PERK kinase) and accordingly can be used for the treatment of cell proliferative disorders, such as cancer, or diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions comprising these compounds.
>> Read More

LXR INVERSE AGONISTS FOR TREATMENT OF CANCER (Fri, 29 Dec 2017)
In some aspects, the present disclosure provides compounds of the formula: (I) or (II) wherein the variables are as defined herein. In some embodiments, these compounds may be used to treat cancer or other hyperproliferative diseases, as well as atherosclerosis and coronary artery disease.
>> Read More

Phenothiazine derivatives and methods of use thereof (Wed, 27 Dec 2017)
<p id="p-0001" num="0000">The present disclosure relates to phenothiazine derivatives such as conjugates of phenothiazine compounds, as well as pharmaceutical compositions thereof. The present disclosure also relates to a method of making and the use of such compounds for treating cancer, e.g., a lung cancer, a colon cancer, breast cancer or pancreatic cancer.</p>
>> Read More

SMALL MOLECULE INHIBITORS OF EGFR AND PI3K (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a quinazoline structure or a quinoline structure which function as dual inhibitors of EGFR proteins and PI3K proteins, and their use as therapeutics for the treatment of cancer and other diseases.</p>
>> Read More

MELAMPOMAGNOLIDE B DIMERS (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">The present disclosure provides dimers of melampomagnolide B (MMB), including carbamate, carbonate, succinic amide, ester and carboxamide dimers of MMB. These derivatives are useful for treating cancer in humans, in particular in treating leukemia, including acute myelogenous leukemia (AML). A compound comprising Formula (1) wherein: Z is independently selected from the group consisting of CH2, O, C(O), and CH, wherein when Z is CH, Z is connected to Y via a double bond and Y is N.</p>
>> Read More

COMPOUNDS, COMPOSITIONS AND METHODS OF USE (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">Herein, compounds, compositions and methods for modulating inclusion formation and stress granules in cells related to the onset of neurodegenerative diseases, musculoskeletal diseases, cancer, ophthalmological diseases, and viral infections are described.</p>
>> Read More

HISTONE DEACETYLASE INHIBITORS (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">In recognition of the need to develop novel therapeutic agents, the present invention provides novel histone deacetylase inhibitors. These compounds include an ester bond making them sensitive to deactivation by esterases. Therefore, these compounds are particularly useful in the treatment of skin disorders. When the compounds reaches the bloodstream, an esterase or an enzyme with esterase activity cleaves the compound into biologically inactive fragments or fragments with greatly reduced activity Ideally these degradation products exhibit a short serum and/or systemic half-life and are eliminated rapidly. These compounds and pharmaceutical compositions thereof are particularly useful in treating cutaneous T-cell lymphoma, neurofibromatosis, psoriasis, hair loss, skin pigmentation, and dermatitis, for example. The present invention also provides methods for preparing compounds of the invention and intermediates thereto.</p>
>> Read More

AGENT CONTAINING FLAVONOID DERIVATIVES FOR TREATING CANCER AND INFLAMMATION (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">A pharmaceutical composition for the prevention and treatment of cancer with specific flavanoid-based compounds selected from among the groups of Flavone, Flavanone and Flavanol, a method for the prevention and treatment of cancer and inflammation using the specific flavonoid-based pharmaceutical compositions, a method for isolating the flavonoid-based pharmaceutical compositions from raw plant material, and a method for synthesizing said specific flavonoid-based pharmaceutical compositions.</p>
>> Read More

POLYMORPH OF GRANATICIN B (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">The present invention provides a crystalline Form A of Compound 1, also referred to as Granaticin B, and pharmaceutically compositions thereof. The present invention also provides methods of treating a microbial infection, or a disease, disorder, or condition associated with abnormal cellular proliferation, using crystalline Form A of Compound 1 or pharmaceutical compositions thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="49.61mm" wi="66.04mm" file="US20170360746A1-20171221-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

ORGANIC ANION TRANSPORTING PEPTIDE-BASED CANCER IMAGING AND THERAPY (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">A dye-drug conjugate for preventing, treating, or imaging cancer having the following structure:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="21.17mm" wi="74.00mm" file="US20170360945A1-20171221-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sub>1 </sub>and R<sub>2 </sub>are independently selected from the group consisting of —H, alkyl, alkyl-sulphonate, alkylcarboxylic, alkylamino, aryl, —SO<sub>3</sub>H, —PO<sub>3</sub>H, —OH, —NH<sub>2</sub>, and -halogen; wherein Y<sub>1 </sub>and Y<sub>2 </sub>is independently selected from the group consisting of alkyl, aryl, aralkyl, alkylsulphonate, alkylcarboxylic, alkylamino, ω-alkylaminium, ω-alkynyl, PEGyl, PEGylcarboxylate, ω-PEGylaminium, ω-acyl-NH, ω-acyl-lysinyl-, ω-acyl-triazole, ω-PEGylcarboxyl-NH—, ω-PEGylcarboxyl-lysinyl, and ω-PEGylcarboxyl-triazole; wherein X is selected from the group consisting of a hydrogen, halogen, CN, Me, NH<sub>2</sub>, SH and OH; and R<sub>3 </sub>and R<sub>4 </sub>are independently a hydrogen, a therapeutic agent, or an imaging moiety, wherein the therapeutic agent is selected from the group consisting of a platinum-based therapeutic agent, a small molecule therapeutic agent, a peptide, a protein, a polymer, an siRNA, a microRNA, and a nanoparticle, wherein the imaging is a radio-isotope selected from the group consisting of F18, I-125, I-124 I-123, I-131, and small molecule labeled with any of these isotopes, or wherein the imaging moiety is a chelator-complexed radioactive isotope, wherein the radioactive isotope is selected from the group consisting of Cu-64, In-111, Tc-99m, Ga-68, Lu-177, Zo-89, Th-227 and Gd-157.</p>
>> Read More

BETA-SUBSTITUTED BETA-AMINO ACIDS AND ANALOGS AS CHEMOTHERAPEUTIC AGENTS AND USES THEREOF (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">β-Substituted β-amino acids, β-substituted β-amino acid derivatives, and β-substituted β-amino acid analogs and (bio)isosteres and their use as chemotherapeutic agents are disclosed. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and (bio)isosteres are selective LAT1/4F2hc substrates and exhibit rapid uptake and retention in tumors expressing the LAT1/4F2hc transporter. Methods of synthesizing the β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and methods of using the compounds for treating cancer are also disclosed. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs exhibit selective uptake in tumor cells expressing the LAT1/4F2hc transporter and accumulate in cancerous cells when administered to a subject in vivo. The β-substituted β-amino acid derivatives and β-substituted β-amino acid analogs and (bio)isosteres exhibit cytotoxicity toward several tumor types.</p>
>> Read More

Substituted Cyclohexylamine Compounds (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">The present disclosure provides substituted cyclohexylamine compounds having Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein R<sup>1</sup>, R<sup>2a</sup>, R<sup>2b</sup>, R<sup>3a</sup>, R<sup>3b</sup>, R<sup>4</sup>, R<sup>5</sup>, and R<sup>7 </sup>are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of SMYD proteins such as SMYD<b>3</b> or SMYD<b>2</b>. Compounds of the present disclosure are especially useful for treating cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.63mm" wi="65.11mm" file="US20170362191A1-20171221-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

NOVEL PYRIMIDINES AS EGFR INHIBITORS AND METHODS OF TREATING DISORDERS (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">The application relates to a compound having Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="63.50mm" file="US20170362204A1-20171221-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">which modulates the activity of EGFR, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which EGFR plays a role.</p>
>> Read More

PHARMACEUTICAL COMPOSITION COMPRISING BICYCLIC NITROGEN-CONTAINING AROMATIC HETEROCYCLIC AMIDE COMPOUND AS ACTIVE INGREDIENT (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">[Problem] Provided is a pharmaceutical composition for treating lung cancer in which mitochondrial Complex I is involved, particularly non-small cell lung cancer.</p> <p id="p-0002" num="0000">[Means for Solution] The inventors of the present invention conducted examinations on a compound having an effect of inhibiting mitochondrial Complex I, and confirmed that a bicyclic nitrogen-containing aromatic heterocyclic amide compound of the present invention has the effect of inhibiting mitochondrial Complex I and that this compound exhibits an anti-tumor effect on mice bearing tumors of non-small cell lung cancer-derived cells, and therefore completed the present invention.</p>
>> Read More

PHARMACEUTICAL COMPOSITION COMPRISING BICYCLIC NITROGEN-CONTAINING AROMATIC HETEROCYCLIC AMIDE COMPOUND AS ACTIVE INGREDIENT (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">[Problem] Provided is a pharmaceutical composition for treating various types of cancer in which mitochondrial Complex I is involved, particularly colorectal cancer, leukemia and/or malignant lymphoma.</p> <p id="p-0002" num="0000">[Means for Solution] As a result of intensive examination for creating a pharmaceutical composition for treating various types of cancer, the inventors of the present invention confirmed that a specific bicyclic nitrogen-containing aromatic heterocyclic amide compound has the effect of inhibiting mitochondrial Complex I and activating AMPK, and that a pharmaceutical composition comprising the compound as an active ingredient has a treatment effect on various types of cancer in which mitochondrial Complex I is involved, particularly colorectal cancer, leukemia and/or malignant lymphoma, and therefore completed the present invention.</p>
>> Read More

COMPOSITION AND METHOD FOR AFFECTING CYTOKINES AND NF-KB (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">The present invention discloses a composition and method for effecting various cytokines and NF-κB by administering an effective amount of a phyto-percolate composition to an individual. In various exemplary embodiments, the composition is claimed to be useful for the effective treatment of inflammation, cancer, and/or various infections including HIV by regulation of various interleukins, such as IL-10 and IL-2, and of transcription factors including NF-κB.</p>
>> Read More

METHOD OF PREVENTING OR REDUCING THE PROGRESSION OF PROSTATE CANCER (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">The embodiments include methods of preventing or reducing the progression of prostate cancer in mammals susceptible to developing prostate cancer, and to methods of reducing the incidence of clinically detected prostate cancer, using compositions containing compounds based on small peptides and a pharmaceutically acceptable carrier. The method includes, but is not limited to, administering the compounds intramuscularly, orally, intravenously, intraprostatically, intrathecally, intratumorally, intranasally, topically, transdermally, etc., either alone or conjugated to a carrier to a mammal in need thereof.</p>
>> Read More

COT MODULATORS AND METHODS OF USE THEREOF (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">The present disclosure relates generally to modulators of Cot (cancer Osaka thyroid) and methods of use and manufacture thereof.</p>
>> Read More

Substituted Piperidine Compounds (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">The present disclosure provides substituted piperidine compounds having Formula (I), and the pharmaceutically acceptable salts and solvates thereof, wherein R<sup>1</sup>, B, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="20.57mm" wi="59.77mm" file="US20170362217A1-20171221-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Site Search