Cancer

ANTI-GP73 ANTIBODIES AND IMMUNOCONJUGATES (Fri, 25 May 2018)
The present invention relates to antigen-binding molecules, preferably antibodies or antigen-binding fragments thereof, that specifically bind to a GP73, or to an antigenic portion thereof, wherein the antigen-binding molecule binds to an epitope within the extracellular part of GP73 that is internalized into a cell usually subsequent to proteolytic cleavage. The invention further relates to immunoconjugates comprising the antigen-binding molecules, in particular the anti-GP73 antibodies, or antigen-binding fragments thereof. The antigen- binding molecules and immunoconjugates of the invention may be administered alone, as a therapeutic conjugate or in combination with other naked antibodies, or with therapeutic agents, or with other immunoconjugates or as a diagnostic conjugate. The present invention also relates to nucleotide sequences encoding anti GP73 antibodies, and immunoconjugates, vectors and host cells containing the nucleotide sequences, and methods of making anti-GP73-antibodies. The antigen-binding molecules, antibodies and compositions of the invention are useful in diagnostic and therapeutic applications for diseases in which expression of GP73 is altered, in particular in which GP73 is overexpressed, such as cancer.
>> Read More

SELF-ASSEMBLED DIBLOCK COPOLYMERS COMPOSED OF PEGMEMA AND DRUG BEARING POLYMERIC SEGMENTS (Fri, 25 May 2018)
This invention relates to polymer drug conjugates according to formula I, and their use for treatment of diseases such as cancer.
>> Read More

NOVEL ANTI-VIRAL AND ANTI-CANCER MOLECULE (Fri, 25 May 2018)
Novel anti-Viral and anti-Cancer molecule containing nucleobase or its derivatives or its analogues attached to an Ascorbic Acid molecule or its derivatives or its analogues with or without an oxygen bond in-between.
>> Read More

NANOPARTICLE CONJUGATES AND USES THEREOF (Fri, 25 May 2018)
The targeted delivery of therapeutic agents to specific cells remains a challenge in drug delivery. Provided herein are nanoparticle-targeting agent conjugates that can be used for the targeted delivery of therapeutic agents to certain cells and target tissues. The conjugates comprise nanoparticles (e.g., metal nanoparticles such as gold nanoparticles) with organic outer shells capable of adsorbing large numbers of therapeutic agents (e.g., small molecule drugs). The nanoparticles are covalently linked to targeting agents (e.g., proteins such as antibodies). The present invention also provides formulations comprising the nanoparticle-targeting agent conjugates, and kits comprising the same. In another aspect, the present invention provides methods of using the conjugates for the delivery of therapeutic agents to cells, and the treatment and/or prevention of diseases (e.g., autoimmune diseases, infectious diseases, proliferative diseases such as cancer). In another aspect, the present invention provides methods of preparing the nanoparticle-targeting agent conjugates described herein.
>> Read More

ANTI-MET ANTIBODIES, BISPECIFIC ANTIGEN BINDING MOLECULES THAT BIND MET, AND METHODS OF USE THEREOF (Fri, 25 May 2018)
Provided herein are antibodies and bispecific antigen-binding molecules that bind MET and methods of use thereof. The bispecific antigen-binding molecules comprise a first and a second antigen-binding domain, wherein the first and second antigen-binding domains bind to two different (preferably non-overlapping) epitopes of the extracellular domain of human MET. The bispecific antigen-binding molecules are capable of blocking the interaction between human MET and its ligand HGF. The bispecific antigen-binding molecules can exhibit minimal or no MET agonist activity, e.g., as compared to monovalent antigen-binding molecules that comprise only one of the antigen-binding domains of the bispecific molecule, which tend to exert unwanted MET agonist activity. Also included are antibody-drug conjugates (ADCs) comprising the antibodies or bispecific antigen-binding molecules provided herein linked to a cytotoxic agent, radionuclide, or other moiety, as well as methods of treating cancer in a subject by administering to the subject a bispecific antigen-binding molecule or an ADC thereof.
>> Read More

2-SUBSTITUTED AMINO-NAPHTH[1,2-D]IMIDAZOL-5-ONE COMPOUNDS OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF CROSS REFERENCE TO RELATED APPLICATIONS (Fri, 25 May 2018)
Provided herein are therapeutic and/or prophylactic compounds for mitochondrial or oxidative stress diseases such as cancer, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, Machado-Joseph disease, spinocerebellar ataxia, Huntington disease, Parkinson disease, Alzheimer disease, myocardial infarction, cerebral infarction, diseases related to aging, diabetes, alcoholic liver injury, chronic obstructive pulmonary disease, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and the like, wherein the compound is represented by formula (1), or reduced forms thereof, or pharmaceutically acceptable salts thereof.
>> Read More

5,6-DIHYDRO-11H-INDOLO[2,3-B]QUINOLIN-11-ONES AS ALK INHIBITORS (Fri, 25 May 2018)
The present disclosure provides compounds represented by Formula( I), and the pharmaceutically acceptable salts and solvates thereof, wherein R1a, R1b, R2a, R2b, R3, R4, R5, R6, R7, E and (B) are as defined as set forth in the specification. The present disclosure also provides compounds of Formula ( I) for use to treat a condition or disorder responsive to inhibition of ALK such as cancer.
>> Read More

INHIBITORS OF CD73-MEDIATED IMMUNOSUPPRESSION (Fri, 25 May 2018)
Compounds that modulate the conversion of AMP to adenosine by 5'- nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5'- nucleotidase, ecto is also provided.
>> Read More

ALKYL PYRROLOPYRIMIDINE ANALOGS AND METHODS OF MAKING AND USING SAME (Fri, 25 May 2018)
The present disclosure is concerned with benzo annulene compounds that are capable of inhibiting a Mer tyrosine kinase and/or a Tyro3 tyrosine kinase and methods of treating a bacterial infection, a viral infection, and/or a disorder of uncontrolled cellular proliferation such as, for example, a cancer, using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
>> Read More

Transplatin derivatives as anticancer agents (Wed, 23 May 2018)
<p id="p-0001" num="0000">The invention is directed to platinum(II) thione complexes of formula (I) and to methods of treating cancer using these complexes.</p>
>> Read More

COMBINATION THERAPY OF AN AFUCOSYLATED CD20 ANTIBODY WITH A CD79b ANTIBODY-DRUG CONJUGATE (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present invention is directed to the combination therapy of an afucosylated anti-CD20 antibody with a CD79b antibody-drug conjugate for the treatment of cancer, especially to the combination therapy of CD20 expressing cancers with an afucosylated humanized B-Ly1 antibody and a CD79b antibody-drug conjugate.</p>
>> Read More

5-ALA DERIVATIVES AND USE THEREOF (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present invention is directed to new 5-ALA derivatives, particles and formulation thereof, related methods of preparation and methods of use thereof. In particular, the invention relates to compounds of the invention, particles and formulation thereof useful in the treatment of a cancer and/or the diagnosis of a cancer cell such as in photodynamic therapy or photodynamic diagnosis.</p>
>> Read More

Site-Specific DNA-Doxorubicin Conjugates Display Enhanced Cytotoxicity to Breast Cancer Cells (Fri, 18 May 2018)
<p id="p-0001" num="0000">Doxorubicin (Dox) is widely used for breast cancer treatment but causes serious side-effects including cardiotoxicity that may adversely impact patient lifespan even if treatment is successful. The present invention relates to selective conjugation of Dox to a single site in a DNA hairpin resulting in a highly stable complex that enables Dox to be used more effectively. Selective conjugation of Dox to G15 in the hairpin loop was verified using site-specific labeling with [2-15N]-2′-deoxyguanosine in conjunction with [1H-15N] 2D NMR while 1:1 stoichiometry for the conjugate was validated by ESI-QTOF mass spectrometry and UV spectroscopy. Molecular modeling indicated covalently bound Dox also intercalated into the stem of the hairpin and stability studies demonstrated the resulting Dox-conjugated hairpin (DCH) complex had a half-life >30 h, considerably longer than alternative covalent and non-covalent complexes. Secondary conjugation of DCH with folic acid (FA) resulted in increased internalization into breast cancer cells. The dual conjugate, DCH-FA, can be used for safer and more effective chemotherapy with Dox and this conjugation strategy can be expanded to include additional anti-cancer drugs.</p>
>> Read More

ADMINISTRATION OF UBIQUITIN-ACTIVATING ENZYME INHIBITOR AND CHEMOTHERAPEUTIC AGENTS (Fri, 18 May 2018)
<p id="p-0001" num="0000">Disclosed are methods for the treatment of cancer in patients in need of such treatment. The methods comprise administering to such a patient an ubiquitin-activating enzyme (UAE) inhibitor such as ((1R,2R,3S,4R)-2,3-dihydroxy-4-(2-(3-(tri-fluoromethylthio)phenyl)pyrazolo [1,5-a]pyrimidin-7-ylamino)cyclopentyl)methyl sulfamate (Compound 1) or a pharmaceutically acceptable salt in combination with one or more chemotherapeutic agents. Also disclosed are medicaments for use in the treatment of cancer.</p>
>> Read More

METHODS OF TREATING PEDIATRIC CANCERS (Fri, 18 May 2018)
<p id="p-0001" num="0000">A method of treating a pediatric cancer in a subject in need thereof. The method includes administering to the subject a therapeutically effective amount of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, or a pharmaceutically acceptable salt thereof, or a combination thereof.</p>
>> Read More

COMBINATION THERAPY WITH A PHOSPHOINOSITIDE 3-KINASE INHIBITOR WITH A ZINC BINDING MOIETY (Fri, 18 May 2018)
<p id="p-0001" num="0000">The invention provides a method of treating cancer in a subject in need thereof, comprising administering to the subject: <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">(a) a compound of Formula I:</li> </ul> </li> </ul> </p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.56mm" wi="72.56mm" file="US20180133223A1-20180517-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt thereof, wherein R is hydrogen or an acyl group; and (b) a BCL-2 inhibitor; wherein the compound of Formula I or pharmaceutically acceptable salt thereof and a BCL-2 inhibitor are administered in amounts which in combination are therapeutically effective. The invention further provides a pharmaceutical composition comprising a compound of Formula I or a pharmaceutically acceptable salt thereof, a BCL-2 inhibitor and a pharmaceutically acceptable carrier or excipient.</p>
>> Read More

METHOD FOR TREATING CANCER (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present invention provides a method for treating or alleviating a symptom of a disorder, e.g., immune evasion, cancer-cell induced immune dysfunction, reduced immune response, lowered inflammation, decreased expression of a major histocompatibility complex (MHC), or cancer, characterized by aberrant, misregulated, or increased Enhancer of Zeste Homolog 2 (EZH2) activity in a cell or subject in need thereof by contacting the cell or administering to the subject a therapeutically effective amount of an EZH2 inhibitor.</p>
>> Read More

NANOPARTICLE CONJUGATES AND USES THEREOF (Fri, 18 May 2018)
<p id="p-0001" num="0000">The targeted delivery of therapeutic agents to specific cells remains a challenge in drug delivery. Provided herein are nanoparticle-targeting agent conjugates that can be used for the targeted delivery of therapeutic agents to certain cells and target tissues. The conjugates comprise nanoparticles (e.g., metal nanoparticles such as gold nanoparticles) with organic outer shells capable of adsorbing large numbers of therapeutic agents (e.g., small molecule drugs). The nanoparticles are covalently linked to targeting agents (e.g., proteins such as antibodies). The present invention also provides formulations comprising the nanoparticle-targeting agent conjugates, and kits comprising the same. In another aspect, the present invention provides methods of using the conjugates for the delivery of therapeutic agents to cells, and the treatment and/or prevention of diseases (e.g., autoimmune diseases, infectious diseases, proliferative diseases such as cancer). In another aspect, the present invention provides methods of preparing the nanoparticle-targeting agent conjugates described herein.</p>
>> Read More

MITRAGYNINE ANALOGS AND USES THEREOF (Fri, 18 May 2018)
<p id="p-0001" num="0000">Described herein are compounds of Formulae (I′)-(II′), compounds of Formulae (I)-(II) and pharmaceutically acceptable salts thereof. Compounds of the present invention are useful for modulating opioid receptor activity. The provided compounds may have both agonistic and antagonistic effect on one or more opioid receptors. Methods of using the compounds for treating or managing pain are also described.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="191.52mm" wi="64.60mm" file="US20180134708A1-20180517-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

BROMODOMAIN INHIBITORS (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present invention relates to substituted heterocyclic derivative compounds, compositions comprising said compounds, and the use of said compounds and compositions for epigenetic regulation by inhibition of bromodomain-mediated recognition of acetyl lysine regions of proteins, such as histones. Said compositions and methods are useful for the treatment of cancer and neoplastic disease.</p>
>> Read More

PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF (Fri, 18 May 2018)
<p id="p-0001" num="0000">Conjugates and compounds for making conjugates which are PBD molecules linked via the N10 position are disclosed, along with the use of the conjugates for treating proliferative diseases, including cancer.</p>
>> Read More

INHIBITION OF GLIADIN PEPTIDES (Fri, 18 May 2018)
<p id="p-0001" num="0000">Novel compounds and methods for the inhibition of biological barrier permeability and for the inhibition of peptide translocation across biological barriers are identified. Assays for determining modulators of biological barrier permeability and for peptide translocation across biological barriers are provided. Methods for treating diseases relating to aberrant biological barrier permeability and peptide translocation across biological barriers are provided. Such diseases include celiac disease, necrotizing enterocolitis, diabetes, cancer, inflammatory bowel diseases, asthma, COPD, excessive or undesirable immune response, gluten sensitivity, gluten allergy, food allergy, rheumatoid arthritis, multiple sclerosis, immune-mediated or type 1 diabetes mellitus, systemic lupus erythematosus, psoriasis, scleroderma and autoimmune thyroid diseases.</p>
>> Read More

ANTI-MET ANTIBODIES, BISPECIFIC ANTIGEN BINDING MOLECULES THAT BIND MET, AND METHODS OF USE THEREOF (Fri, 18 May 2018)
<p id="p-0001" num="0000">Provided herein are antibodies and bispecific antigen-binding molecules that bind MET and methods of use thereof. The bispecific antigen-binding molecules comprise a first and a second antigen-binding domain, wherein the first and second antigen-binding domains bind to two different (preferably non-overlapping) epitopes of the extracellular domain of human MET. The bispecific antigen-binding molecules are capable of blocking the interaction between human MET and its ligand HGF. The bispecific antigen-binding molecules can exhibit minimal or no MET agonist activity, e.g., as compared to monovalent antigen-binding molecules that comprise only one of the antigen-binding domains of the bispecific molecule, which tend to exert unwanted MET agonist activity. Also included are antibody-drug conjugates (ADCs) comprising the antibodies or bispecific antigen-binding molecules provided herein linked to a cytotoxic agent, radionuclide, or other moiety, as well as methods of treating cancer in a subject by administering to the subject a bispecific antigen-binding molecule or an ADC thereof.</p>
>> Read More

PRODUCTION MODULE AND METHOD, IMAGING DEVICE AND METHOD AND MRI AND/OR MRS PROGRAMS (Fri, 18 May 2018)
<p id="p-0001" num="0000">The invention relates to a module (<b>6</b>) for producing an MRI and/or MRS reference signal (S<b>0</b>), characterized in that the module comprises: <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">a first receiving input (<b>621</b>) for receiving of an MRI and/or MRS synchronization signal (S<b>3</b>),</li> <li id="ul0002-0002" num="0000">a second receiving input (<b>612</b>) for receiving of a time signal (S<b>8</b>) of external stimulation,</li> <li id="ul0002-0003" num="0000">supply means (<b>62</b>) for supplying of a prescribed signal (RV) representing an MRI and/or MRS virtual object (RVV),</li> <li id="ul0002-0004" num="0000">generating means for generating of the MRI and/or MRS reference signal (S<b>0</b>), for temporally varying the MRI and/or MRS reference signal (S<b>0</b>) in the same way as a time characteristic determined from the time signal (S<b>8</b>) of external stimulation and in synchronization with the MRI and/or MRS synchronization signal (S<b>3</b>),</li> <li id="ul0002-0005" num="0000">a supply output (<b>632</b>) for supplying of the MRI and/or MRS reference signal (S<b>0</b>).</li> </ul> </li> </ul> </p>
>> Read More

METHODS TO INDUCE TARGETED PROTEIN DEGRADATION THROUGH BIFUNCTIONAL MOLECULES (Fri, 18 May 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

AZA-PHENALENE-3-KETONE DERIVATIVE, PREPARATION METHOD THEREOF, AND ITS APPLICATION AS PARP INHIBITOR (Fri, 18 May 2018)
<p id="p-0001" num="0000">Disclosed are an aza-phenalene-3-ketone derivative, a preparation method thereof and its application as a PARP inhibitor. The aza-phenalene-3-ketone derivative has the following structure:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.79mm" wi="36.66mm" file="US20180134722A1-20180517-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R is hydrogen, methyl, ethyl, isopropyl, benzyl or 3-methyl-3-butenyl. The aza-phenalene-3-ketone derivative has very high activity for inhibiting PARP, thereby providing a good basis for new drug research of developing a nitrogen-doped phenalene-3-ketone compound as PARP inhibitor to treat cancer.</p>
>> Read More

CORTISTATIN ANALOGUES, SYNTHESES, AND USES THEREOF (Fri, 18 May 2018)
<p id="p-0001" num="0000">New cortistatin compounds and pharmaceutically acceptable salts and pharmaceutically acceptable compositions thereof are provided. These compounds can be used to treat a disorder mediated by CDK8 and/or CDK19 kinase or by the Mediator Complex generally. In particular, the compounds can be used, for example, to treat a disorder such as a tumor, cancer, or a disorder associated with angiogenesis.</p>
>> Read More

MITO-HONOKIOL COMPOUNDS AND METHODS OF SYNTHESIS AND USE THEREOF (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present invention provides mito-honokiol compounds, pharmaceutical compositions thereof, and methods of using the mito-honokiol compounds in the treatment of cancer.</p>
>> Read More

METHODS OF SYNTHESIZING SUBSTITUTED PURINE COMPOUNDS (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure.</p>
>> Read More

SALTS AND PRODRUGS OF 1-METHYL-D-TRYPTOPHAN (Fri, 18 May 2018)
<p id="p-0001" num="0000">Presently provided are indoximod prodrug and salt compounds and pharmaceutical compositions comprising salts and prodrugs of indoximod, that produce enhanced plasma concentration and exposure to indoximod compared to direct administration of indoximod, in patients in need of treatment of immunosuppression mediated by the indoleamine-2,3-dioxygenase pathway, such as patients with cancer or chronic infectious diseases.</p>
>> Read More

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS (Fri, 18 May 2018)
<p id="p-0001" num="0000">Chemical entities based on quinoxaline that are kinase inhibitors are described. Specifically quinoxaline derivatives of Formula I, containing a diarylamide or diarylurea substructure that inhibit Braf mutant kinase activity, pharmaceutical compositions containing the inhibitor compounds and methods of treatment of cancer comprising administering an effective amount of the Braf inhibitor compound are described.</p>
>> Read More

COMPOUNDS FOR THE TREATMENT OR PREVENTION OF BREAST CANCER (Fri, 18 May 2018)
<p id="p-0001" num="0000">It discloses compounds for the treatment and prevention of breast cancer, which are specifically 2-phenyl benzoselenazole compounds, pharmaceutically acceptable salts thereof and prodrugs thereof. The present invention further discloses pharmaceutical compositions containing the compounds and applications of the compounds in preparing medicines for the treatment and prevention of breast cancer in mammals. The compounds of the present invention can effectively inhibit or reduce the growth or proliferation of breast cancer cells in mammals, with no inhibition effect on the growth of part of the tested cell lines except for the breast cancer cell lines, and are highly selective.</p>
>> Read More

THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF (Fri, 18 May 2018)
<p id="p-0001" num="0000">The invention provides compounds that are useful for treating or preventing cancer.</p>
>> Read More

BARBITURATE AND THIOBARBITURATE COMPOUNDS FOR USE IN CANCER THERAPY (Fri, 18 May 2018)
<p id="p-0001" num="0000">Provided are methods and compositions for use in therapy, and in particular for treating cancer, preferably drug-resistant cancer, and/or radiation resistant cancer. The compounds may be used for reducing tumor size in a mammalian subject and for inducing apoptosis in a tumor cell. The methods are effective on tumor cells that are resistant to drugs such as temozolomide, doxorubicin, and geldanamycin, as well as non-resistant tumor cells. Further provided are barbiturate and thiobarbiturates diene compounds for use in treating cancer, and uses, methods and compositions relating to these compounds.</p>
>> Read More

1,4-PYRIDONE BICYCLIC HETEROARYL COMPOUNDS (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present invention relates to 1,4-pyridone bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.</p>
>> Read More

Imidazo[4,5-c]quinolin-2-one Compounds and Their Use in Treating Cancer (Fri, 18 May 2018)
<p id="p-0001" num="0000">The specification generally 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="32.77mm" wi="75.69mm" file="US20180134699A1-20180517-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">and pharmaceutically acceptable salts thereof, where Q, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and R<sup>5 </sup>have any of the meanings defined herein. The specification also relates to the use of such compounds and salts thereof to treat or prevent ATM kinase mediated disease, including cancer. The specification further relates to crystalline forms of compounds of imidazo[4,5-c]quinolin-2-one compounds and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds and salts; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; intermediates useful in the manufacture of such compounds and salts; and to methods of treating ATM kinase mediated disease, including cancer, using such compounds and salts.</li> </ul> </li> </ul> </p>
>> Read More

METHODS OF SYNTHESIZING SUBSTITUTED PURINE COMPOUNDS (Fri, 18 May 2018)
<p id="p-0001" num="0000">The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure.</p>
>> Read More

TARGETED SELECTION OF PATIENTS FOR TREATMENT WITH CORTISTATIN DERIVATIVES (Fri, 18 May 2018)
<p id="p-0001" num="0000">A method for the targeted selection and treatment of patients with a tumor or cancer, comprising (i) determining whether the patient has a RUNX1 pathway impairment; and if so (ii) administering an effective amount of a cortistatin or its pharmaceutically acceptable salt or oxide, optionally in a pharmaceutically acceptable composition.</p>
>> Read More

NOVEL CLASS OF QUINOLONE HETEROCYCLIC AROMATIC MOLECULES FOR CANCER TREATMENT (Fri, 18 May 2018)
The invention is directed to new class of quinolone heterocyclic aromatic molecules (Renotinibs) and their use in the treatment of cancer, in particular, cancer that harbor abnormal human epidermal growth factor receptors (EGFRs).
>> Read More

3-SUBSTITUTED PROPIONIC ACIDS AS ALPHA V INTEGRIN INHIBITORS (Fri, 18 May 2018)
The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αν- containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of ay- containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
>> Read More

CYCLOBUTANE- AND AZETIDINE-CONTAINING MONO AND SPIROCYCLIC COMPOUNDS AS ALPHA V INTEGRIN INHIBITORS (Fri, 18 May 2018)
The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αv- containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of av-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
>> Read More

INDAZOLE DERIVATIVES AS αV INTEGRIN ANTAGONISTS (Fri, 18 May 2018)
The present invention provides compounds of Formula (Ia) or (Ib): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αV- containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αV-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
>> Read More

AZOLE AMIDES AND AMINES AS ALPHA V INTEGRIN INHIBITORS (Fri, 18 May 2018)
The present invention provides compounds of Formula (I): (Formula (I)), or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are inhibitors to αv-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αv-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
>> Read More

PYRROLE AMIDES AS ALPHA V INTEGRIN INHIBITORS (Fri, 18 May 2018)
The present invention provides compounds of Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are inhibitors to αv-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αv-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.
>> Read More

COMPOSITIONS AND METHODS OF MODULATING ANTI-TUMOR IMMUNITY (Fri, 18 May 2018)
The present invention provides methods of treating cancer by combination therapy with CDK4/6 inhibitors and immune checkpoint inhibition.
>> Read More

RESTORATION OF TUMOR SUPPRESSION USING MRNA-BASED DELIVERY SYSTEM (Fri, 18 May 2018)
Compositions and methods for treating cancer that include administering a therapeutically effective amount of a tumor suppressor mRNA complexed with a delivery vehicle as described herein, e.g., a nanoparticle.
>> Read More

ECKOL DERIVATIVES, METHODS OF SYNTHESIS AND USES THEREOF (Fri, 18 May 2018)
Provided herein are eckol derivatives, methods of synthesis thereof and pharmaceutical compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, Alzheimer's disease, microbial infections, obesity, diabetes, cancer or inflammation using the compounds and pharmaceutical compositions disclosed herein.
>> Read More

ACTIVIN RECEPTOR TYPE IIA VARIANTS AND METHODS OF USE THEREOF (Fri, 18 May 2018)
The invention features polypeptides that include an extracellular ActRlla variant. In some embodiments, a polypeptide of the invention includes an extracellular ActRlla variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving weakness and atrophy of muscles, e.g., Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, inclusion body myositis, amyotrophic lateral sclerosis, sarcopenia; or cancer cachexia; or metabolic diseases, e.g., obesity, Type-1 diabetes, or Type-2 diabetes.
>> Read More

ACTIVIN RECEPTOR TYPE IIA VARIANTS AND METHODS OF USE THEREOF (Fri, 18 May 2018)
The invention features polypeptides that include an extracellular ActRlla variant. In some embodiments, a polypeptide of the invention includes an extracellular ActRlla variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving bone damage, e.g., primary osteoporosis, secondary osteoporosis, osteopenia, osteopetrosis, facture, bone cancer or cancer metastasis-related bone loss, Paget's disease, renal osteodystrophy, treatment-related bone loss, diet- related bone loss, bone loss associated with the treatment of obesity, low gravity-related bone loss, or immobility-related bone loss.
>> Read More

DEGRADATION OF PROTEIN KINASES BY CONJUGATION OF PROTEIN KINASE INHIBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE (Fri, 18 May 2018)
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 protein kinases (e.g., Bcr-Abl). The present application also relates to methods for the targeted degradation of one or more protein kinases through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to one or more protein kinases which can be utilized in the treatment of disorders modulated by protein kinases.
>> Read More

ATG7 INHIBITORS AND THE USES THEREOF (Fri, 18 May 2018)
Disclosed are chemical entities which are compounds of formula (I) : or a pharmaceutically acceptable salt thereof, wherein R1, R2, and Ra have the values described herein. Chemical entities according to the disclosure can be useful as inhibitors of ATG7. Further provided are pharmaceutical compositions comprising a chemical entity of the disclosure and methods of using the compositions in the treatment of cancer.
>> Read More

HETEROCYCLIC MODULATORS OF LIPID SYNTHESIS (Fri, 18 May 2018)
Compounds that are fatty acid synthesis modulators are provided. The compounds may be used to treat disorders characterized by disregulation of the fatty acid synthase function by modulating the function and/or the fatty acid synthase pathway. Methods are provided for treating such disorders including viral infections, such as hepatitis C infection, cancer and metabolic disorders, such as non-alcoholic steatohepatitis (NASH).
>> Read More

HUMAN PLASMA-LIKE MEDIUM (Fri, 18 May 2018)
In some aspects, described herein are cell culture media that are useful for in vitro culture of mammalian cells. The culture media contain a variety of small organic compounds that are found in normal adult human blood. Also described are methods of using the culture media for a variety of purposes. Also described are methods of treating cancer.
>> Read More

INHIBITORS OF CANCER INVASION, ATTACHMENT, AND/OR METASTASIS (Fri, 18 May 2018)
Provided herein are, inter alia, compositions that bind to a PDZ1 domain of MDA-9/Syntenin (syndecan binding protein: SDCBP), thereby inhibiting MDA-9/Syntenin activity, and methods of use of same. The compositions and methods provided herein are useful for treating cancer and preventing cancer metastasis, particularly in cancers that have increased MDA-9/Syntenin expression.
>> Read More

COMBINATION OF A BRD4 INHIBITOR AND AN ANTIFOLATE FOR THE THERAPY OF CANCER (Fri, 18 May 2018)
The present invention relates to the combination of a BRD4 inhibitor with an antifolate (particularly an MTHFD1 inhibitor) for use in the treatment or prevention of cancer. The invention also relates to an antifolate (particularly an MTHFD1 inhibitor) for use in resensitizing a BRD4 inhibitor-resistant cancer to the treatment with a BRD4 inhibitor. The invention further provides a pharmaceutical composition comprising a BRD4 inhibitor, an antifolate (particularly an MTHFD1 inhibitor), and a pharmaceutically acceptable excipient. Moreover, the invention provides a method of assessing the susceptibility or responsiveness of a subject to the treatment with a BRD4 inhibitor, wherein the subject has been diagnosed as suffering from cancer or is suspected of suffering from cancer, the method comprising determining the level of nuclear folate and/or the level of expression of MTHFD1 in a sample obtained from the subject.
>> Read More

PYRIMIDINONE DERIVATIVES AS CDC7 INHIBITORS (Fri, 18 May 2018)
The present invention relates to compounds of formula I as defined herein, and salts and solvates thereof, that function as inhibitors of cell division cycle 7 (Cdc7) kinase enzyme activity Formula (I). The present invention also relates 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 Cdc7 kinase activity is implicated.
>> Read More

ANTI-CD46 ANTIBODIES AND METHODS OF USE (Fri, 18 May 2018)
Disclosed herein are methods of treating a subject having a cancer characterized by a modification at biomarker 1q21, which comprises administering to the subject a therapeutically effective amount of an anti-CD46 antibody.
>> Read More

BICYCLIC HETEROARYL DERIVATIVES AS MNK1 AND MNK2 MODULATORS AND USES THEREOF (Thu, 17 May 2018)
The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.
>> Read More

HEDGEHOG ANTAGONISTS HAVING ZINC BINDING MOIETIES (Thu, 17 May 2018)
The present invention provides compounds which antagonize hedgehog signaling and inhibit HDAC activity. The compounds can be used in methods of treating proliferative diseases and disorders such as cancer.
>> Read More

ZINC-γ-PGA COMPOSITIONS AND METHODS FOR TREATING CANCER (Sat, 12 May 2018)
The invention relates to pharmaceutical compositions comprising a zinc2+ salt and a γ-polyglutamic acid carrier, and, optionally, an NF-kB inhibitor as a tumor-sensitizing agent, and methods for using such compositions to treat tumors in patients. Methods include administering a liquid dosage form or a solid dosage form of a therapeutically effective amount of a Zn(ll) salt and a γ-polyglutamic acid carrier to a patient in need thereof. Methods of treating a broad spectrum of human tumors, including tumors with a drug-resistant phenotype, using the disclosed compositions are provided. Tumors that respond to the pharmaceutical compositions disclosed herein include neuroendocrine (neuroblastoma), gastric, uterine, and lung tumors.
>> Read More

COMPOUNDS FOR MALT1 DEGRADATION (Sat, 12 May 2018)
Provided herein are bifunctional compounds that inhibit MALTl and/or promote targeted ubiquitination for the degradation of MALTl. In particular, provided are compounds that can bind MALTl, a protein whose activity is responsible for constitutive NF-KB signaling in certain cancers (e.g., activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL)), and can assist in its degradation by recruiting an E3 ubiquitin ligase (e.g., Cereblon, VHL), which can ubiquitinate MALTl, marking it for proteasome degradation. Also provided are pharmaceutical compositions comprising the bifunctional compounds, methods of treating cancer with the bifunctional compounds, methods of promoting the degradation of MALTl, and methods of binding E3 ubiquitin ligase activity in a subject by administering a compound or composition described herein.
>> Read More

COMBINATION THERAPY WITH A PHOSPHOINOSITIDE 3-KINASE INHIBITOR WITH A ZINC BINDING MOIETY (Sat, 12 May 2018)
The invention provides a method of treating cancer in a subject in need thereof, comprising administering to the subject: (a) a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein R is hydrogen or an acyl group; and (b) a BCL-2 inhibitor; wherein the compound of Formula I or pharmaceutically acceptable salt thereof and a BCL-2 inhibitor are administered in amounts which in combination are therapeutically effective. The invention further provides a pharmaceutical composition comprising a compound of Formula I or a pharmaceutically acceptable salt thereof, a BCL-2 inhibitor and a pharmaceutically acceptable carrier or excipient.
>> Read More

SUBSTITUTED QUINOLINES AND METHODS FOR TREATING CANCER (Sat, 12 May 2018)
Substituted quinoline compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat, prevent or ameliorate cancer are provided.
>> Read More

AGENTS AND METHODS FOR TREATING CREB BINDING PROTEIN-DEPENDENT CANCERS (Sat, 12 May 2018)
Single chain peptides comprising either a cell penetrating HIV-TAT peptide sequence and a MYB:CBP complex interfering peptide sequence from MYB, or compsiring a cell penetrating HIV-TAT peptide sequence, a CBP binding peptide sequence from CREB and a MYB:CBP complex interfering peptide sequence from MYB, are provided for use in preventing MYB:CBP complex formation and downstream events leading to cancer, in particular a leukemia. Both L-amino acid single chain peptides and retro-inverso single chain peptides are provided.
>> Read More

6-SUBSTITUTED DERIVATIVES OF HEXAMETHYLENE AMILORIDE AS INHIBITORS OF uPA AND USES THEREOF (Sat, 12 May 2018)
The present invention broadly relates to 6-substituted derivatives of hexamethylene amiloride, the preparation thereof, and their use in the treatment of diseases such as cancer.
>> Read More

IMMUNOMODULATORS (Sat, 12 May 2018)
The present disclosure provides compounds which are immunomodulators and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.
>> Read More

COMBINATIONS COMPRISING A PYRROLIDINE-2,5-DIONE IDO1 INHIBITOR AND AN ANTI-BODY (Fri, 11 May 2018)
<p id="p-0001" num="0000">Combinations of an IDO1 inhibitor (e.g., a 3-(5-fluoro-1H-indol-3-yl)pyrrolidine-2,5-dione compound), with an anti-PD1 antibody or anti-PD-L1 antibody, and an anti-4-1BB antibody, as selected anti-cancer or anti-viral agents are provided. Also provided are use of these combinations for the treatment and/or prevention of cancer and endometriosis.</p>
>> Read More

THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE (Fri, 11 May 2018)
<p id="p-0001" num="0000">Provided are compounds useful for treating cancer and methods of treating cancer, for example an advanced solid tumor, such as a glioma, or angioimmunoblastic T-cell lymphoma (AITL).</p>
>> Read More

SUBSTITUTED QUINAZOLINES FOR INHIBITING KINASE ACTIVITY (Fri, 11 May 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

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS (Fri, 11 May 2018)
<p id="p-0001" num="0000">Chemical entities that are bufalin derivatives, pharmaceutical compositions and methods of treatment of cancer are described.</p>
>> Read More

MODIFIED BINDING PROTEINS INHIBITING THE VEGF-A RECEPTOR INTERACTION (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present invention relates to binding proteins specific for VEGF-A, in particular to recombinant binding proteins comprising a polyethylene glycol moiety and a binding domain, which inhibits VEGF-Axxx binding to VEGFR-2. Examples of such recombinant binding proteins are proteins which comprise an ankyrin repeat domain with the desired binding specificity, and a polyethylene glycol moiety. The binding proteins are useful in the treatment of cancer and other pathological conditions, e.g. eye diseases such as age-related macular degeneration.</p>
>> Read More

TRAIL RECEPTOR-BINDING AGENTS AND USES OF SAME (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present invention discloses TRAIL receptor-binding agents, their therapeutic effects on tumor inhibition in vitro and in vivo, alone or in combination with various chemotherapeutic agents. In particular, the present invention discloses methods for the treatment of cancer, comprising administrating a TRAIL receptor binding agent of the present technology, alone or in combination with a chemotherapeutic agent.</p>
>> Read More

ANTIBODY-VACCINE ENGINEERED CONSTRUCTS (AVEC) (Fri, 11 May 2018)
<p id="p-0001" num="0000">Hereby, we disclose and claim, the concept, designs, enabling technologies, and utility for therapy of patients suffering from cancer, of a novel class of biomolecularly engineered, synthetic molecules: antibody-vaccine engineered constructs (AVEC). They comprise the main functional domains (antibodies and vaccines) and the supporting domains (linkers and reporters). Their mechanisms of actions rely upon antibody dependent redirecting, accelerating, and amplifying of the prophylactic or natural vaccination induced immune response (ADRAAVIR) from the initially elicited by vaccination towards the finally aimed by therapies. The routes of administration to the patients, pharmacokinetics, pharmacodynamics, pharmacogenomics, and therapeutic efficacies are resultant of those of the pertinent antibodies and vaccines assembled within AVEC.</p>
>> Read More

TREATMENT OF CANCER USING CHIMERIC ANTIGEN RECEPTORS (Fri, 11 May 2018)
<p id="p-0001" num="0000">The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.</p>
>> Read More

COMPOSITIONS FOR TREATING CANCER AND METHODS FOR MAKING THE SAME (Fri, 11 May 2018)
<p id="p-0001" num="0000">Described herein are compositions and methods relating to chemotherapeutic agent conjugates and the treatment of cancer.</p>
>> Read More

METHODS AND COMPOSITIONS FOR THERANOSTIC NANOPARTICLES (Fri, 11 May 2018)
<p id="p-0001" num="0000">Disclosed are compositions and methods for identifying a solid tumor cell target. Compositions and methods for treating prostate cancer are also disclosed. Further, cancer therapeutic compositions comprising CT20p are disclosed. Nanoparticles that are conjugated with a targeting ligand that is a substrate for a solid tumor-specific cell protein are disclosed.</p>
>> Read More

DENDRI-TAC AND THEIR USE AS THERANOSTICS (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present invention relates to novel amphiphilic dendrimers, hereafter denoted Dendri-TAC. The present invention also relates to perfluorocarbon nanoemulsions stabilized by these amphiphilic dendrimers and their uses for in vivo diagnostic and/or for therapy, notably as theranostic tools, for detection and/or treatment of cancer.</p>
>> Read More

COMPOSITIONS FOR ENHANCING DELIVERY OF AGENTS ACROSS THE BLOOD BRAIN BARRIER AND METHODS OF USE THEREOF (Fri, 11 May 2018)
<p id="p-0001" num="0000">Compositions and methods for improved delivery of active agents to the brain are provided. The compositions typically include a nanocarrier, such as a polymeric nanoparticle, liposome, or nanolipagel or are in the form of a conjugate. The nanocarriers or conjugates typically include three components: a targeting moiety; a blood brain barrier blood-brain barrier modulator (BBB modulator), loaded into, attached to the surface of, and/or enclosed within a nanocarrier; and an additional active agent loaded into, attached to the surface of, and/or enclosed within a nanocarrier. The targeting moiety, which is typically conjugated to or otherwise dismodulator played on the surface of the nanocarrier, can be, for example, a moiety that preferentially or specifically targets brain cells or tissue, cancer cells, or a combination thereof.</p>
>> Read More

ARYLCYCLOPROPYLAMINE BASED DEMETHYLASE INHIBITORS OF LSD1 AND THEIR MEDICAL USE (Fri, 11 May 2018)
<p id="p-0001" num="0000">The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula (I) as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection. Thus, in one specific aspect the invention relates to formulas (II), (III), (IV), (V), (VI), (VII), (VIII), (IX).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="213.19mm" wi="74.34mm" file="US20180127406A1-20180510-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="122.68mm" wi="73.91mm" file="US20180127406A1-20180510-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

INHIBITORS OF LYSINE SPECIFIC DEMETHYLASE-1 (Fri, 11 May 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

EPOXYAZULENE DERIVATIVES USEFUL FOR TREATING CANCER AND DIABETES (Fri, 11 May 2018)
<p id="p-0001" num="0000">Disclosed is a compound of formula (I) in which R<sup>1</sup>-R<sup>5 </sup>and X<sup>1 </sup>are as described herein. Also provided are methods of using a compound of formula (I), including a method of treating cancer and a method of treating diabetes.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.07mm" wi="52.41mm" file="US20180127433A1-20180510-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

C5, C6 SUBSTITUTED AND/OR FUSED OXINDOLES AS ANTI-CANCER AGENTS AND PROCESS FOR PREPARATION THEREOF (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present invention describes the C5,C6 Substituted and/or fused oxindole compounds useful as anti-cancer agents and process for preparation thereof. Particularly the present invention relates to C5,C6 Substituted and/or fused oxindole compounds of formula I.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.88mm" wi="66.97mm" file="US20180127365A1-20180510-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">A=C, CH, CH<sub>2</sub>, None</li> <li id="ul0002-0002" num="0000">B=C or CH part of open chain and/or cyclic alkyl/aryl/heteroaryl moiety</li> <li id="ul0002-0003" num="0000">G=alkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalkyl, alkoxy, aryloxy-all these optionally substituted with one or more substituents</li> <li id="ul0002-0004" num="0000">D=O, N, S, OH, SH, NH, None</li> <li id="ul0002-0005" num="0000">Z=C, CH<sub>2 </sub></li> <li id="ul0002-0006" num="0000">Ring E=aryl/heteroaryl/cycloalkyl optionally substituted with one or more substituents</li> <li id="ul0002-0007" num="0000">Ring C=aryl/heteroaryl/cycloalkyl optionally substituted with one or more substituents</li> <li id="ul0002-0008" num="0000">L=H, alkyl, alkoxy, halogen, CN, OH, amino, NO<sub>2 </sub></li> <li id="ul0002-0009" num="0000">K=H, alkyl, alkoxy, halogen, CN, OH, amino, NO<sub>2 </sub></li> <li id="ul0002-0010" num="0000">X=H, alkyl, alkoxy, halogen, CN, OH, amino, NO<sub>2 </sub></li> <li id="ul0002-0011" num="0000">Y=H, alkyl, alkoxy, halogen, CN, OH, amino, NO<sub>2 </sub></li> <li id="ul0002-0012" num="0000">R1=H, alkyl</li> <li id="ul0002-0013" num="0000">R2=H, alkyl, halogen, CN, NO<sub>2</sub>, alkoxy, amino, OH</li> </ul> </li> </ul> </p>
>> Read More

LSD1 Inhibitors (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present invention relates to compounds that inhibit LSD1 activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of treating cancer using the compounds and pharmaceutical compositions of the present invention.</p>
>> Read More

IMIDAZOLYL TRICYCLIC ENONES AS ANTIOXIDANT INFLAMMATION MODULATORS (Fri, 11 May 2018)
<p id="p-0001" num="0000">Disclosed herein are compounds of the formula: (I), wherein the variables are defined herein. Also provided are pharmaceutical compositions thereof. In some aspects, the compounds and compositions provided herein may be used as antioxidant inflammation modulators. In some aspects, the present disclosure provides methods wherein the compounds and composition described herein are used for the treatment of diseases and disorders associated with inflammation and cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.23mm" wi="57.74mm" file="US20180127380A1-20180510-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

TETRASUBSTITUTED ALKENE COMPOUNDS AND THEIR USE (Fri, 11 May 2018)
<p id="p-0001" num="0000">Disclosed herein are compounds, or pharmaceutically acceptable salts thereof, and methods of using the compounds for treating breast cancer by administration to a subject in need thereof a therapeutically effective amount of the compounds or pharmaceutically acceptable salts thereof. The breast cancer may be an ER-positive breast cancer and/or the subject in need of treatment may express a mutant ER-α protein.</p>
>> Read More

NOVEL CLASS OF QUINOLONE HETEROCYCLIC AROMATIC MOLECULES FOR CANCER TREATMENT (Fri, 11 May 2018)
<p id="p-0001" num="0000">The invention is directed to new class of quinolone heterocyclic aromatic molecules (Renotinibs) and their use in the treatment of cancer, in particular, cancer that harbor abnormal human epidermal growth factor receptors (EGFRs).</p>
>> Read More

INHIBITORS OF RAS AND METHODS OF USE THEREOF (Fri, 11 May 2018)
<p id="p-0001" num="0000">Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="17.44mm" wi="52.75mm" file="US20180127396A1-20180510-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein A, B, R″, Q, W, X, Y, Z, n<sup>2 </sup>and <img id="CUSTOM-CHARACTER-00001" he="3.56mm" wi="2.79mm" file="US20180127396A1-20180510-P00001.TIF" alt="custom-character" img-content="character" img-format="tif"/> are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.</p>
>> Read More

SUBSTITUTED PURINE COMPOUNDS (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present invention relates to substituted purine compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer, by administering these compounds and pharmaceutical compositions to subjects in need thereof.</p>
>> Read More

5-SUBSTITUTED INDAZOLE-3-CARBOXAMIDES AND PREPARATION AND USE THEREOF (Fri, 11 May 2018)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease, fibrotic disorders, cartilage (chondral) defects, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, and neurological conditions/disorders/diseases linked to overexpression of DYRK1A.</p>
>> Read More

ECKOL DERIVATIVES, METHODS OF SYNTHESIS AND USES THEREOF (Fri, 11 May 2018)
<p id="p-0001" num="0000">Provided herein are eckol derivatives, methods of synthesis thereof and pharmaceutical compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, Alzheimer's disease, microbial infections, obesity, diabetes, cancer or inflammation using the compounds and pharmaceutical compositions disclosed herein.</p>
>> Read More

SUBSTITUTED BENZIMIDAZOLES AND BENZOPYRAZOLES AS CCR(4) ANTAGONISTS (Fri, 11 May 2018)
<p id="p-0001" num="0000">Benzimidazole, benzopyrazole and benzotriazole compounds are provided which bind to CCR(4) and are useful for the treatment of diseases such as allergic diseases, autoimmune diseases, graft rejection and cancer.</p>
>> Read More

ISOXAZOLYL SUBSTITUTED BENZIMIDAZOLES (Fri, 11 May 2018)
<p id="p-0001" num="0000">A compound which is a benzimidazolyl isoxazole of formula (I): wherein: R<sup>0 </sup>and R, which are the same or different, are each H or C<sub>1-6 </sub>alkyl; R<sup>9</sup>, R<sup>9 </sup>and R<sup>9</sup>, which are the same or different, are each H or F; X is -(alk<sub>n</sub>-, -alk-C(═O)—NR—, -alk-NR—C(═O)— or -alk-C(═O)—; R<sup>1 </sup>is selected from —S(═O)<sub>2</sub>R′; a 4- to 6-membered, C-linked heterocyclic group which is unsubstituted or substituted; and an N-linked spiro group of the following formula: R<sup>2 </sup>and R<sup>2′</sup>, which are the same or different, are each H or C<sub>1-6 </sub>alkyl, or R<sup>2 </sup>and R<sup>2′</sup> form, together with the C atom to which they are attached, a C<sub>3-6 </sub>cycloalkyl group; R<sup>3 </sup>and R<sup>3</sup>, which are the same or different, are each H, C<sub>1-6 </sub>alkyl, OH or F; R<sup>4 </sup>is phenyl or a 5- to 12-membered, N-containing heteroaryl group and is unsubstituted or substituted; alk is C<sub>1-6 </sub>alkylene; R′ is C<sub>1-6 </sub>alkyl; and n is 0 or 1; or a pharmaceutically acceptable salt thereof. The compound has activity in modulating the activity of p300 and/or CBP and is used to treat cancer, particularly prostate cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.08mm" wi="63.58mm" file="US20180127402A1-20180510-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

PYRAZOLYL QUINOXALINE KINASE INHIBITORS (Fri, 11 May 2018)
<p id="p-0001" num="0000">The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.</p>
>> Read More

Algorithms for Disease Diagnostics (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present invention relates to compositions and methods for molecular profiling and diagnostics for genetic disorders and cancer, including but not limited to gene expression product markers associated with cancer or genetic disorders. In particular, the present invention provides algorithms and methods of classifying cancer, for example, thyroid cancer, methods of determining molecular profiles, and methods of analyzing results to provide a diagnosis.</p>
>> Read More

BICYCLIC HETEROCYCLES AS FGFR INHIBITORS (Thu, 10 May 2018)
The present invention relates to bicyclic heterocycles of formula I, and pharmaceutical compositions of the same, that are inhibitors of one or more FGFR enzymes and are useful in the treatment of FGFR-associated diseases such as cancer.
>> Read More

METHODS FOR INCREASING EFFICACY OF FOLR1 CANCER THERAPY (Thu, 10 May 2018)
Methods to improve the success of cancer therapies that target the human folate receptor 1 are provided. Kits comprising reagent useful in the methods are further provided.
>> Read More

Anthracene-9, 10-dione dioxime compound prodrugs and their uses (Wed, 09 May 2018)
<p id="p-0001" num="0000">Chemical agents, such as disulfonamide derivatives of fluorene, anthracene, xanthene, dibenzosuberone and acridine, and similar heterocyclic ring structures; including, salts thereof that act as anti-cancer and anti-tumor agents, along with methods for preparing such agents, as well as pharmaceutical compositions containing such agents as active ingredients and methods of using these as therapeutic agents.</p>
>> Read More

MODULATORS OF FARNESOID X RECEPTOR AND METHODS FOR THE USE THEREOF (Fri, 04 May 2018)
<p id="p-0001" num="0000">Compounds, compositions and methods are provided for treating the FXR-mediated disease or process in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound claimed, wherein the FXR-mediated disease or condition linked to chronic liver diseases such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis; gastrointestinal diseases; cardiovascular diseases; metabolic diseases such as diabetes and obesity; inflammation, or cancer etc.</p>
>> Read More

DEMETHYLPENCLOMEDINE ANALOGS AND THEIR USE AS ANTI-CANCER AGENTS (Fri, 04 May 2018)
<p id="p-0001" num="0000">This disclosure concerns novel demethylpenclomedine analogs. Also disclosed are pharmaceutical compositions and methods for using such compositions to treat hyperproliferative disorders. In one embodiment the analogs are represented by the formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.98mm" wi="27.94mm" file="US20180117022A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

BROMODOMAIN AND EXTRA-TERMINAL PROTEIN INHIBITOR COMBINATION THERAPY (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present disclosure relates generally to compositions and methods of treating neoplastic diseases or cancers, such as glioblastoma and non-Hodgkin's lymphomas, or other cancers in which the subject suffers from an advanced solid tumor, comprising a combination of, or administering a combination of, a bromodomain and extra-terminal protein (BET) inhibitor and at least one chemotherapeutic agent, which does not inhibit BET directly. The BET inhibitor/chemotherapeutic agent combination, or combination therapy, can yield synergistic effects, thereby increasing the effectiveness of the cancer treatment as compared with the administration of either the BET inhibitor or the chemotherapeutic agent alone.</p>
>> Read More

6-AMINO-PURIN-8-ONE COMPOUNDS (Fri, 04 May 2018)
<p id="p-0001" num="0000">Compounds of formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.34mm" wi="69.85mm" file="US20180117048A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1 </sup>is C<sub>1-6</sub>alkylamino, C<sub>1-6</sub>alkoxy, or C<sub>3-7</sub>cycloalkyloxy; m is an integer having a value of 3 to 6; n is an integer having a value of 0 to 4; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.</p>
>> Read More

DEUTERIUM-ENRICHED ISOINDOLINONYL-PIPERIDINONYL CONJUGATES AND OXOQUINAZOLIN-3(4H)-YL-PIPERIDINONYL CONJUGATES AND METHODS OF TREATING MEDICAL DISORDERS USING SAME (Fri, 04 May 2018)
<p id="p-0001" num="0000">The invention provides deuterium-enriched isoindolinonyl-piperidinonyl conjugates, deuterium-enriched oxoquinazolin-3(4H)-yl-piperidinonyl conjugates, pharmaceutical compositions, and methods of using such conjugates and pharmaceutical compositions to treat cancer, angiogenesis disorders, immune disorders, and other medical disorders.</p>
>> Read More

Binding Agents That Modulate the Hippo Pathway and Uses Thereof (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to agents that modulate the Hippo pathway and Hippo pathway signaling, such as antibodies and soluble receptors, as well as to methods of using the agents for the treatment of diseases such as cancer.</p>
>> Read More

ANTIBODIES SPECIFIC TO GLYCOSYLATED PD-L1 AND METHODS OF USE THEREOF (Fri, 04 May 2018)
<p id="p-0001" num="0000">Antibodies that bind specifically to glycosylated PD-L1 relative to unglycosylated PD-L1 are provided. Antibodies that recognize specific epitopes of glycosylated PD-L1 protein and can block the binding of PD-L1 to PD-1 are provided. In some aspects, PD-L1 polypeptides comprising glycosylated amino acid residues at amino and carboxy terminal positions of the PD-L1 extracellular domain are also provided. Methods for making and using such antibodies and polypeptides (e.g., for the treatment of cancer) are also provided.</p>
>> Read More

CAR T-CELLS FOR THE TREATMENT OF B7-H4 EXPRESSING SOLID TUMORS (Fri, 04 May 2018)
<p id="p-0001" num="0000">CAR cells and antibodies targeting human B7-H4 expressed on many human cancers including but not limited to breast ovarian, and renal cancers are described as a new method of cancer treatment. It is proposed that B7-H4 CAR cells are safe and effective in patients and can be used to treat human tumors expressing the B7-H4 surface protein.</p>
>> Read More

SHMT Inhibitors (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to a method for the treatment of cancer or an autoimmune disorder, comprising the administration of a serine hydroxymethyltransferase (SHMT) inhibitor, and in particular the administration of pyrazolopyran compounds of Formula (VI) as presently described, wherein the compounds are capable of inhibiting a mammalian SHMT, such as human SHMT1 and/or SHMT2. The treatment method further comprises the optional administration of an additional agent as a rescue therapy to reduce toxicity, wherein said agent may be chosen from formate, a formate salt, folinic acid, formate ester, or leucovorin.</p>
>> Read More

Method of Using dihydro-resveratrol or its stilbenoid derivatives and/or chemical variants in treatment of tumorous pathologies (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to a polyphenol derivative of the stilbenoid family, namely trans-3,5,4′-trihydroxybibenzyl, also known as dihydro-resveratrol, as a remedial agent. In particular, the present invention presents the usage of dihydro-resveratrol or its derivatives/chemical variants in the manufacture of a medicament for the treatment of tumors or cancers. The dihydrostilbenes can be used in the treatment or delay of progression of a cancer in a patient or used in a pharmaceutical formulation for the aforementioned purposes.</p>
>> Read More

SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF (Fri, 04 May 2018)
<p id="p-0001" num="0000">This invention provides novel 3-amino propanamide selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), 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

THERAPEUTIC AGENTS (Fri, 04 May 2018)
<p id="p-0001" num="0000">A compound of formula (I) or a compound of formula (II) or pharmaceutically acceptable salts thereof, wherein R1-R7 and X are as defined in the description, and the use of these compounds in therapy, in particular in treating cancer or as an inhibitor of the interaction of the MDM2 protein with p53.</p>
>> Read More

HETEROCYCLIC DERIVATIVES MODULATING ACTIVITY OF CERTAIN PROTEIN KINASES (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to novel heterocyclic derivatives having general formula (I) and their therapeutic use for diseases such as cancer, inflammation, pain, autoimmune diseases or neurodegenerative diseases like Alzheimer's or Parkinson's disease that can be treated by modulation of certain protein kinases. Compounds of formula (I) can be used for treatment of patients who do not respond to kinase inhibition therapy that comprises currently available medications.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.86mm" wi="59.86mm" file="US20180118691A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

COMPOUNDS FOR TREATMENT OF CANCER (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to colchicine-binding site compounds having anti-cancer activity, compositions comprising the same, and their use for treating various forms of cancer.</p>
>> Read More

SELECTIVE HDAC6 INHIBITORS (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention provides a compound having the structure:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="11.51mm" wi="34.63mm" file="US20180118709A1-20180503-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</li> <li id="ul0002-0002" num="0000">R<sub>1 </sub>is halogen, —NR<sub>5</sub>R<sub>6</sub>, —NR<sub>5</sub>—C(═O)—R<sub>6</sub>, —NH—C(═O)—OR<sub>7</sub>, —OR<sub>7</sub>, —NO<sub>2</sub>, —CN, —SR<sub>7</sub>, —SO<sub>2</sub>R<sub>7</sub>, —CO<sub>2</sub>R<sub>7</sub>, CF<sub>3</sub>, —SOR<sub>7</sub>, —POR<sub>7</sub>, —C(═S)R<sub>7</sub>, —C(═O)—NR<sub>5</sub>R<sub>6</sub>, —CH<sub>2</sub>—C(═O)—NR<sub>5</sub>R<sub>6</sub>, —C(═NR<sub>5</sub>)R<sub>6</sub>, —P(═O)(OR<sub>5</sub>)(OR<sub>6</sub>), —P(OR<sub>5</sub>)(OR<sub>6</sub>), —C(═S)R<sub>7</sub>, C<sub>1-5 </sub>alkyl, C<sub>2-5 </sub>alkenyl, C<sub>2-5 </sub>alkynyl, aryl, heteroaryl, or heterocyclyl, <ul id="ul0003" list-style="none"> <li id="ul0003-0001" num="0000">wherein R<sub>5</sub>, R<sub>6</sub>, and R<sub>7 </sub>and are each, independently, H, C<sub>1-5 </sub>alkyl, C<sub>2-5 </sub>alkenyl, C<sub>2-5 </sub>alkynyl, heteroalkyl, hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C<sub>1-5 </sub>alkyl-aryl, or C<sub>1-5 </sub>alkyl-NH-aryl;</li> </ul> </li> <li id="ul0002-0003" num="0000">Ar<sub>1 </sub>is phenyl or thiophene;</li> <li id="ul0002-0004" num="0000">wherein when Ar<sub>1 </sub>is phenyl, then R<sub>1 </sub>is other than —C(═O)—NR<sub>5</sub>R<sub>6</sub>, where one of R<sub>5 </sub>or R<sub>6 </sub>is phenyl or quinoline and the other of R<sub>5 </sub>or R<sub>6 </sub>is hydroxyalkyl, or where one of R<sub>5 </sub>or R<sub>6 </sub>is quinoline and the other of R<sub>5 </sub>or R<sub>6 </sub>is H; and</li> <li id="ul0002-0005" num="0000">wherein when Ar<sub>1 </sub>is phenyl, then R<sub>1 </sub>is other than —NR<sub>5</sub>—C(═O)—R<sub>6</sub>, where one of R<sub>5 </sub>is H and R<sub>6 </sub>is quinoline, <br/> or a pharmaceutically acceptable salt thereof. </li> </ul> </li> </ul> </p>
>> Read More

HISTONE DEMETHYLASE INHIBITORS (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates generally to compositions and methods for treating cancer and neoplastic diseases. Provided herein are substituted imidazole-pyridine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of histone demethylase enzymes. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as pancreatic cancer, prostate cancer, breast cancer, bladder cancer, lung cancer, gastric cancer, leukemia and/or melanoma and the like.</p>
>> Read More

PYRIMIDINE DERIVATIVES (Fri, 04 May 2018)
<p id="p-0001" num="0000">Compounds of Formula I or II</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="49.78mm" wi="69.85mm" file="US20180118721A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which R1, X1 and X2 have the meanings indicated in claim <b>1</b>, are MTH1 inhibitors and can be employed, inter alia, in the treatment of cancer.</p>
>> Read More

IDO Inhibitors (Fri, 04 May 2018)
<p id="p-0001" num="0000">Presently provided are IDO inhibitors and pharmaceutical compositions thereof, useful for modulating an activity of indoleamine 2,3-dioxygenase; treating indoleamine 2,3-dioxygenase (IDO) mediated immunosuppression; treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine-2,3-dioxygenase; enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent; treating tumor-specific immunosuppression associated with cancer; and treating immunosupression associated with an infectious disease.</p>
>> Read More

SUBSTITUTED QUINAZOLINES AS INHIBITORS OF KRAS G12C (Fri, 04 May 2018)
<p id="p-0001" num="0000">Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.72mm" wi="65.02mm" file="US20180118757A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R<sup>1</sup>, R<sup>2a</sup>, R<sup>3a</sup>, R<sup>3b</sup>, R<sup>4a</sup>, R<sup>4b</sup>, G<sup>1</sup>, G<sup>2</sup>, L<sup>1</sup>, L<sup>2</sup>, m<sup>1</sup>, m<sup>2</sup>, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.</p>
>> Read More

COMPOSITIONS AND METHODS FOR ALTERING SECOND MESSENGER SIGNALING (Fri, 04 May 2018)
<p id="p-0001" num="0000">The invention relates to compositions, methods, kits, and assays related to the use and/or exploitation of isomers of cGAMP as well as the structure of the enzyme cGAS.</p>
>> Read More

PHARMACOLOGICALLY ACTIVE COMPOUNDS (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to compounds of formula II</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.73mm" wi="69.85mm" file="US20180117032A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein X, Y, R<sub>2</sub>, R<sub>3</sub>, R<sub>4 </sub>and Ar are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1—also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.</p>
>> Read More

COMBRETASTATIN ANALOGS (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates novel heterocyclic analogs of combretastatin, their synthesis, and their use as anti-cancer compounds. In particular, compounds of Formula (I), Formula (II), and Formula (V) are provided.</p>
>> Read More

Substituted Quinazoline Derivatives as DNA Methyltransferase Inhibitors (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to compounds of the following formula (I) and pharmaceutically acceptable salts and solvates thereof, their methods of preparation, their use as a drug, notably in the treatment of cancer, and pharmaceutical compositions containing such compounds.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.10mm" wi="69.85mm" file="US20180118717A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

NOVEL ARYL-CYANOGUANIDINE COMPOUNDS (Fri, 04 May 2018)
<p id="p-0001" num="0000">The present invention relates to protein-lysine N-methyltransferase SMYD2 (SET and MYND domain-containing protein 2) inhibitors, in particular SMYD2-inhibitory substituted cyanoguanidine-pyrazolines of general formula (I), wherein R<sup>1</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5 </sup>and n have the meaning as described and defined herein, as well as to pharmaceutical compositions comprising compounds according to the invention and to their prophylactic and therapeutic use for hyperproliferative disorders, in particular for cancer, respectively tumour disorders. The present invention furthermore relates to the use of SMYD2 inhibitors for benign hyperplasias, atherosclerotic disorders, sepsis, autoimmune disorders, vascular disorders, viral infections, neurodegenerative disorders, inflammatory disorders, atherosclerotic disorders and the control of male fertility.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="53.09mm" wi="68.07mm" file="US20180118722A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

6,7,8,9-TETRAHYDRO-3H-PYRAZOLO[4,3-F]ISOQUINOLINE DERIVATIVES USEFUL IN THE TREATMENT OF CANCER (Fri, 04 May 2018)
The specification relates to compounds of Formula (I) and to pharmaceutically acceptable salts thereof, to processes and intermediates used for their preparation, to pharmaceutical compositions containing them and to their use in the treatment of cell proliferative disorders.
>> Read More

MODULATORS OF HEDGEHOG (HH) SIGNALLING PATHWAY (Fri, 04 May 2018)
There are described compounds of formula (I): and there use as a medicament in the treatment of conditions involving abnormal activation and/or malfunction of the of the hedgehog pathway, such as cancer, fibrosis and chronic graft-versus-host disease (cGVHD).
>> Read More

HYPERPOLARIZED [3- 13C]ACETOACETATE AND METHODS OF USING THE SAME (Fri, 04 May 2018)
The present invention relates to hyperpolarized [3-13C]acetoacetate. Provided are [3-13C]acetoacetate and compositions comprising said [3-13C]acetoacetate. Further provided are methods of preparing and using hyperpolarized [3- 13C]acetoacetate in the determination of the spatial and temporal distribution and metabolism of [3-13C]acetoacetate and/or its metabolites in a cell or subject, preferably by magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and/or magnetic resonance spectroscopic imaging (MRSI), whereby conditions, diseases, or disorders associated with the metabolism of acetoacetate and/or other ketone bodies can be diagnosed. The conditions, diseases, or disorders to be diagnosed preferably are cancer, diabetes, cardiovascular diseases, or neurodegenerative diseases.
>> Read More

DEUTERATED N-(5-((4-ETHYLPIPERAZIN-1-YL)METHYL) PYRIDIN-2-YL)-5-FLUORO-4-(4-FLUORO-1-ISOPROPYL-2-METHYL-1H-BENZO[d]IMIDAZOL-6-YL)PYRIMIDIN-2-AMINE (Fri, 04 May 2018)
The present invention is related to compounds of Formula (I): (I) or a pharmaceutically acceptable salt thereof; wherein: Y1, Y2, Y3, Y4, Y4,, Y5, Y5,, Y6,Y6,, Y7, Y7,,Υ8, Y8', Y9, Y9', Y10, Y10', YI0", Y11, Y12, Y13, Y14, Y I4', Y14", Υ15, Y16, Υ16', Y16", Y17, Y17' and Y17" are selected from the group consisting of hydrogen or deuterium, wherein at least one of Y1, Y2, Y3, Y4, Y4,,Y5 Y5,, Y6, Y6,, Y7, Y7,, Y8, Y8', Y9, Y9', Y10, Y10', Y10", Υ11, Y12, Y13, Y14, Y14', Y14", Y15, Y16, Y16', Y16", Y17, Y17', and Y17'' is deuterium; and each carbon is independently optionally replaced with 13C. It also relates to pharmaceutical compositions comprising the compounds of Formula (I) and the use of these compounds as selective CDK4/6 inhibitors with the potential for treatment of pRb-positive tumor types including HR (hormone-receptor)-positive aid HER2 (human epidermal growth factor receptor 2)- negative breast cancer, melanoma, liposarcoma and non-small-cell lung cancer, alone or in combination with additional agents.
>> Read More

DEUTERATED 7-CYCLOPENTYL-N, N-DIMETHYL-2-((5-(PIPERAZIN-1-YL)PYRIDIN-2-YL)AMINO)-7H-PYRROLO[2,3-D]PYRIMDINE-6-CARBOXAMIDE (Fri, 04 May 2018)
The present invention is related to compounds of Formula (I): (I) or a pharmaceutically acceptable salt thereof; wherein: Y1, Y2, Y3, Y4, Y4,, Y5, Y5,; Y6, Y6,, Y7, Y7,, Y8, Y9, Y10, Y10,, Y10,,, Y11, Y11,, Y11,,, Y12, Y12,, Y13, Y13,, Y14, Y14,, Y15, Y15, and Y16 are selected from the group consisting of hydrogen or deuterium, wherein at least one of Y1, Y2, Y3, Y4, Y4,, Y5, Y5,; Y6, Y6,, Y7, Y7,, Y8, Y9, Y10, Y10,, Y10,,, Y11, Y11,, Y11,,, Y12, Y12,, Y13, Y13,, Y14, Y14,, Y15, Y15, and Y16 is deuterium; and each carbon is independently optionally replaced with l3C. It also relates to pharmaceutical compositions comprising the compounds of Formula (I) and the use of these compounds as selective CDK4/6 inhibitors with the potential for treatment of pRb-positive tumor types including HR-positive and HER2 -negative breast cancer in combination with additional agents (i.e. letrozole).
>> Read More

POLYOXOMETALATE COMPLEXES AND USES IN MANAGING CANCER (Fri, 04 May 2018)
The disclosure relates polyoxometalate complexes and uses in the management, treatment, or prevention of cancer. In certain embodiments, the polyoxometalate complexes comprise polydentate oxygen bridging ligands such as those of the following formula: [POM{(OCH2)3CX}2], [M6O13{(OCH2)3CX}2], [V6O13{(OCH2)3CX}2], salts, or derivatives thereof wherein POM is a polyoxometalate, M is a metal, and X is defined herein. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising polyoxometalate complexes disclosed herein.
>> Read More

BROMODOMAIN AND EXTRA-TERMINAL PROTEIN INHIBITOR COMBINATION THERAPY (Fri, 04 May 2018)
The present disclosure relates generally to compositions and methods of treating neoplastic diseases or cancers, such as glioblastoma and non-Hodgkin's lymphomas, or other cancers in which the subject suffers from an advance solid tumor, comprising a combination of, or administering a combination of, a bromodomain and extra-terminal protein BET inhibitor and at least on echemotherapeutic agent, which does not inhibit BET directly. The BET inhibitor/chemotherapeutic agent combination, or combination therapy, can yield syngergistic effects, thereby increasing the effectiveness of the cancer treatment as compared with the administration of either the BET inhibitor or the chemotherapeutic agent alone.
>> Read More

COMPOSITIONS AND ASSOCIATED METHODS OF MESOPOROUS NANOPARTICLES COMPRISING PLATINUM-ACRIDINE MOLECULES (Fri, 04 May 2018)
Large-pore mesoporous silica nanoparticles (MSN) were prepared and functionalized to serve as a robust and biocompatible delivery platform for platinum-acridine (PA) anticancer agents. The material showed a high loading capacity for the dicationic, hydrophilic hybrid agent [PtCl(en)(N-[acridin-9-ylaminoethyl]-N-methylpropionamidine)] dinitrate salt (P1 A1) and virtually complete retention of payload at neutral pH in a high-chloride buffer. In acidic media mimicking the pH inside the cells' lysosomes, rapid, burst-like release of P1 A1 from the nanoparticles is observed. Coating of the materials in phospholipid bilayers resulted in nanoparticles with greatly improved colloidal stability. The lipid and carboxylate- modified nanoparticles containing 40 wt.% drug caused S phase arrest and inhibited cell proliferation in pancreatic cancer cells at submicromolar concentrations similar to carrier-free P1A1. One feature of the nanoparticle-delivered P1A1 was that the payload did not escape from the acidified lysosomal vesicles into the cytoplasm, but was shuttled to the nuclear membrane and released into the nucleus.
>> Read More

METHODS AND COMPOSITIONS FOR IDENTIFYING AND TREATING PATIENTS WITH SMALL CELL LUNG CANCER (Fri, 04 May 2018)
Described herein are methods and compositions useful in detecting, diagnosing and treating small cell lung cancer. Transgenic animal models and cell lines are disclosed for the study of a small cell lung cancer subtype. Methods of screening and identifying active agents for the treatment of a small cell lung cancer subtype as well as methods of identifying patients susceptible to treatment with aurora kinase inhibitors are also provided.
>> Read More

COMPOUNDS AND METHODS FOR TREATING CANCER (Fri, 04 May 2018)
Substituted hydrazone compounds, methods of making such compounds and metal complexes thereof, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds and metal complexes to treat, prevent or ameliorate cancer are provided.
>> Read More

COMPOSITONS AND METHODS FOR THE TREATMENT OF CANCER (Fri, 04 May 2018)
This disclosure provides compositions and methods for treating cancer or inducing an immune response to the cancer in a subject by administering to the subject an effective amount of an isoaspartylated protein or a fragment thereof or an antibody that binds specifically to an isoaspartylated protein or a fragment thereof. In another aspect, the disclosure also provides a pharmaceutical composition, comprising, consisting essentially of, or yet further consisting of an effective amount of the isoaspartylated protein or a fragment thereof or antibody that binds specifically to an isoaspartylated protein or a fragment thereof; and a pharmaceutically acceptable carrier.
>> Read More

SMALL MOLECULE INHIBITORS OF NEK2 AND USES THEREOF (Fri, 04 May 2018)
This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having an imidazole pyrimidine structure which function as inhibitors of NEK2 protein, and their use as therapeutics for the treatment of cancer and other diseases.
>> Read More

GRP94 SELECTIVE INHIBITORS AND USES THEREOF (Fri, 04 May 2018)
The present technology provides compounds according to Formula I or Formula III as well as compositions including such compounds useful for the treatment of metastatic cancer and/or glaucoma.
>> Read More

METHODS OF TREATMENT FOR MYELOID LEUKEMIA (Fri, 04 May 2018)
Embodiments of the present disclosure provide for methods of treating cancer (e.g., leukemia), pharmaceutical compositions for treating cancer, methods of modulating cancer progression and development, and the like.
>> Read More

COMPOSITIONS AND METHODS FOR TREATING EZH2-MEDIATED CANCER (Fri, 04 May 2018)
Methods for designing bivalent compounds which selectively degrade/disrupt EZH2 and compositions and methods of using such degraders/disruptors to treat EZH2-mediated cancer are provided.
>> Read More

IMIDAZO-PYRIMIDONE COMPOUNDS, AND PREPARATION METHOD AND APPLICATION THEREOF (Thu, 03 May 2018)
The present invention discloses compounds of formula (I), imidazopyrimidine ketones, wherein n, R and Ar are as described in the specifications. This invention also discloses the preparations and applications of these compounds. Whereas these compounds and pharmaceutically acceptable salts thereof can stimulate the body to produce tumor necrosis factor- related apoptosis-inducing ligands, while avoiding the drawbacks of existing cancer treatments based on recombinant proteins and antibodies. Thus, they can provide novel options for the treatment of related tumors.
>> Read More

Process for preparing substituted quinolin-4-ol compounds (Wed, 02 May 2018)
<p id="p-0001" num="0000">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.</p>
>> Read More

ANTHRACYCLINE PRODRUGS AND METHODS OF MAKING AND USING THE SAME (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">Therapeutically effective prodrug compounds for the prevention and treatment of cancer and pharmaceutical compositions containing these compounds as well as methods of making and using these compounds.</p>
>> Read More

ANTIPROLIFERATIVE COMPOUNDS AND CONJUGATES MADE THEREFROM (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">A compound capable of inhibiting cell proliferation, having a structure according to formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.04mm" wi="76.12mm" file="US20180110873A1-20180426-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein the variables in formula (I) are as defined in the specification. Such compounds are useful as anti-cancer agents, especially in antibody-drug conjugates.</p>
>> Read More

ANTI-C-MET ANTIBODY AND ANTI-C-MET ANTIBODY-CYTOTOXIC DRUG CONJUGATE AND PHARMACEUTICAL USE THEREOF (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">Provided are an anti-c-Met antibody or an antigen binding fragment thereof, and an anti-c-Met antibody-cytotoxic drug conjugate, wherein the antibody or antigen binding fragment thereof is a chimeric antibody or a humanized antibody. Also provided are pharmaceutical compositions containing the humanized anti-c-Met antibody or antigen binding fragment thereof, the antibody-cytotoxic drug conjugate, or pharmaceutically acceptable salts or solvents thereof, that are used in the treatment of cancer.</p>
>> Read More

Heterodimers of Glutamic Acid (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">Compounds of Formula (Ia)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="26.75mm" wi="65.62mm" file="US20180111895A1-20180426-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R is a C<sub>6</sub>-C<sub>12 </sub>substituted or unsubstituted aryl, a C<sub>6</sub>-C<sub>12 </sub>substituted or unsubstituted heteroaryl, a C<sub>1</sub>-C<sub>5 </sub>substituted or unsubstituted alkyl or —NR′R′, <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000">Q is C(O), O, NR′, S, S(O)<sub>2</sub>, C(O)<sub>2</sub>(CH2)p</li> <li id="ul0001-0002" num="0000">Y is C(O), O, NR′, S, S(O)<sub>2</sub>, C(O)<sub>2</sub>(CH2)p</li> <li id="ul0001-0003" num="0000">Z is H or C<sub>1</sub>-C<sub>4 </sub>alkyl,</li> <li id="ul0001-0004" num="0000">R′ is H, C(O), S(O)<sub>2</sub>, C(O)<sub>2</sub>, a C<sub>6</sub>-C<sub>12 </sub>substituted or unsubstituted aryl, a C<sub>6</sub>-C<sub>12 </sub>substituted or unsubstituted heteroaryl or a C<sub>1</sub>-C<sub>6 </sub>substituted or unsubstituted alkyl, when substituted, aryl, heteroaryl and alkyl are substituted with halogen, C<sub>6</sub>-C<sub>12 </sub>heteroaryl, —NR′R′ or COOZ, which have diagnostic and therapeutic properties, such as the treatment and management of prostate cancer and other diseases related to NAALADase inhibition. Radiolabels can be incorporated into the structure through a variety of prosthetic groups attached at the X amino acid side chain via a carbon or hetero atom linkage.</li> </ul> </p>
>> Read More

Crystalline Forms of Cabozantinib Phosphate And Cabozantinib Hydrochloride (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">The present invention relates to crystalline forms of cabozantinib phosphoric acid salt and cabozantinib hydrochloric acid salt and to a method for their preparation. Furthermore, the invention relates to pharmaceutical compositions comprising said crystalline forms and their use as anti-cancer medicaments. Cabozantinib, i.e. N-{4-[(6,7-dimethoxy-4-quinolinyl)oxy]phenyl}-N′-(4-fluorophenyl)-1,1-cyclopropanedicarboxamide is represented by the chemical structure: Formula.</p>
>> Read More

DIMERIC QUINACRINE DERIVATIVES AS AUTOPHAGY INHIBITORS FOR CANCER THERAPY (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">The invention provides dimeric quinacrine derivatives and related compounds and compositions, methods of treatment and syntheses. The novel compounds exhibit unexpected anticancer activity and are useful in the treatment of a variety of autophagy-related disorders.</p>
>> Read More

N2-(2-METHOXYPHENYL)PYRIMIDINE DERIVATIVE, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION FOR CANCER PREVENTION OR TREATMENT CONTAINING SAME AS ACTIVE INGREDIENT (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">The present invention relates to a N2-(2-methoxyphenyl)pyrimidine derivative, a preparation method thereof, and a pharmaceutical composition for the prevention or treatment of cancer comprising the same as an active ingredient. The N2-(2-methoxyphenyl)pyrimidine derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention is very effective in suppressing anaplastic lymphoma kinase (ALK) activity and as a result it can improve the effectiveness of treatment on cancer cells having anaplastic lymphoma kinase (ALK) fusion proteins such as EML4-ALK and NPM-ALK, so that it can be effectively used as a pharmaceutical composition for preventing or treating cancer.</p>
>> Read More

STK4 INHIBITORS FOR TREATMENT OF HEMATOLOGIC MALIGNANCIES (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">The 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="24.38mm" wi="61.21mm" file="US20180111916A1-20180426-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">which modulate the activity of a kinase (e.g., STK4), a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease or disorder associated with the modulation of a kinase, such as STK4.</p>
>> Read More

BENZIMIDAZOLE DERIVATES USEFUL AS INHIBITORS OF MAMMALIAN HISTONE DEACETYLASE ACTIVITY (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">A compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the compound. The compound is useful in therapy, for the treatment of disorders mediated by HDAC6, such as autoimmune disorders, neurodegenerative disorders and hyperproliferative disorders, such as cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.48mm" wi="69.85mm" file="US20180110755A1-20180426-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Cabozantinib Salts And Their Use As Anti-Cancer Agents (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">The present invention relates to crystalline forms of cabozantinib succinate (Form A) and cabozantinib acetate (Form A-1) and to pharmaceutical compositions comprising said crystalline forms and their use as anti-cancer medicaments.</p>
>> Read More

Curcumin Conjugates and Methods of Use Thereof (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">Curcumin-based conjugates and methods of use thereof are provided. Pharmaceutical compositions including an effective amount of one or more curcumin conjugates are also provided. In particular embodiments, the compositions are formulated for oral delivery. The conjugates and pharmaceutical compositions thereof can be administered to a subject in need thereof to treat a host of diseases and disorders including but not limited to, cancer, inflammation, and microbial growth.</p>
>> Read More

5-HT2B Antagonists (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">The invention provides novel compounds and compositions comprising a 5-HT<sub>2B </sub>antagonist 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="69.85mm" file="US20180111908A1-20180426-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and related methods for treating a person having a disorder characterized by undesirable 5-HT<sub>2B </sub>receptor signaling, such as migraine, irritable bowel syndrome (IBS), pulmonary arterial hypertension (PAH), fibrosis, hepatocellular cancer, a small intestinal neuroendocrine tumor, cardiovascular disorders, and gastrointestinal (GI) tract disorders.</p>
>> Read More

PYRIDYL BENZOTHIOPHENES AS KINASE INHIBITORS (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">This invention is directed to compounds, which are useful as protein kinase (PK) inhibitors and can be used to treat such diseases as cancer, blood vessel proliferative disorders, fibrotic disorders, mesangial cell proliferative disorders, metabolic diseases inflammatory disorders and neurodegenerative disorders.</p>
>> Read More

DIHYDRO-2H-BENZO[b][1,4]OXAZINE SULFONAMIDE AND RELATED COMPOUNDS FOR USE AS AGONISTS OF RORy AND THE TREATEMENT OF DISEASE (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">The invention provides dihydro-2H-benzo[b] [1,4]oxazine sulfonamide and related compounds, pharmaceutical compositions, methods of promoting RORγ activity, methods of increasing the amount of IL-17 in a subject, and methods of treating cancer and other medical disorders using such compounds.</p>
>> Read More

MEDICAL USES AND METHODS FOR TREATING CANCER USING MONOPOLAR SPINDLE 1 (MPS1) KINASE INHIBITORS (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">Medical uses and methods are provided for treating cancer using monopolar spindle 1 (MPS1) kinase inhibitors. Methods and uses for selecting MPS1 kinase inhibitors for use in treating cancer in a subject are provided, both in the initial selection of MPS1 kinase inhibitors and for addressing the development of acquired drug resistance that occur in the course of treatment.</p>
>> Read More

Methods and Systems for Predicting Colorectal Cancer Incidence and Mortality (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">Disclosed are methods and systems that uses GlycA concentration in biosamples to evaluate risks of CRC incidence and mortality.</p>
>> Read More

7-(MORPHOLIN-4-YL)PYRAZOLE[1,5-A]PYRIMIDINE DERIVATIVES WHICH ARE USEFUL FOR THE TREATMENT OF IMMUNE OR INFALMMATORY DISEASES OR CANCER (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">A compound of the general formula (I) wherein Y represents —CH<sub>2</sub>— or >C=0; R<sup>1 </sup>is selected from the group consisting of A1, A2 and A3; R<sup>2 </sup>represents dioxothiomorpholino moiety B1, piperazinyl moiety B2, azetidinyl moiety B3, or piperidinyl moiety B4; R<sup>3 </sup>is selected from the group consisting of H, halogen, and C1-C4 alkyl; R<sup>4 </sup>is selected from the group consisting of C1-C4 alkyl, C3-C4-cycloalkyl, C1-C4 alkyl substituted with C1-C4 alkoxy, and CHF<sub>2</sub>, and their pharmaceutically acceptable salts. Pharmaceutical compositions comprising said compounds and their use in the treatment of diseases of immune system, inflammatory diseases and cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="240.62mm" wi="56.81mm" file="US20180111939A1-20180426-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Chlorin e6 Derivative and Pharmaceutically Acceptable Salt Thereof and Process for Preparing and Use of the Same (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">Chlorin e6 derivatives and pharmaceutically acceptable salt thereof, as well as preparation and use thereof, which belongs to the medicine field. The chlorin e6 ether amino acid derivative has general structural formula I and optical isomers thereof. The preparation process has etherification of 3-vinyl in chlorin e6, A peptide is produced from 15-carboxylethyl and amino acid. The chlorin e6 ether amino acid derivative and pharmaceutically acceptable salt thereof can be used as a photodynamic anti-tumor drug. Compared with the prior similar photosensitizer Talaporfin used in clinic, the chlorin e6 ether amino acid derivative of the present application possess improved photodynamic anti-tumor activities and a high ratio of darktoxicity-phototoxicity. The prepared new photodynamic anti-tumor drugs has photodynamic anti-cancer drugs, drugs for photodynamic treatment of benign vascular diseases, such as age-related macular degeneration and naevus flammeus, and drugs for photodynamic treatment of condyloma <i>acuminata</i>.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="53.09mm" wi="60.88mm" file="US20180111945A1-20180426-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

4,6-PYRIMIDINYLENE DERIVATIVES AND USES THEREOF (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., lung cancer, breast cancer, leukemia, lymphoma, melanoma, multiple myeloma, Ewing's sarcoma, osteosarcoma, brain cancer, neuroblastoma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase (e.g. a protein kinase (e.g. a cyclin-dependent kinase (CDK) (e.g. CDK7, CDKl2, or CDKl3) or a lipid kinase such as a phosphatidylinositol-5-phosphate 4-kinase (PIP4K) (e.g., PI5P4Kα, PI5P4Kβ, or PI5P4Kγ)) in the subject.</p>
>> Read More

CAR T-CELL THERAPY DIRECTED TO LHR FOR THE TREATMENT OF SOLID TUMORS (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">Provided herein are novel anti-LHR chimeric antigen receptor (CAR), cells or compositions comprising the same, vector or plasmid encoding anti-LHR CAR, and methods for producing the same, or using the same for detecting or treating ovarian cancer or prostate cancer. Also provided herein are anti-LHR antibody, compositions comprising the same, nucleic acid sequence encoding the same, and a kit for detecting LHR.</p>
>> Read More

ANTI-MUC16 ANTIBODIES AND USES THEREOF (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">Provided herein are compositions, methods, and uses involving antibodies that immunospecifically bind glycosylated forms of MUC16, a tethered mucin protein. Also provided herein are uses and methods for managing, treating, or preventing disorders, such as cancer.</p>
>> Read More

POLY(BETA-AMINO ESTER)-CO-POLYETHYLENE GLYCOL (PEG-PBAE-PEG) POLYMERS FOR GENE AND DRUG DELIVERY (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">Polyethylene glycol (PEG)-b-poly(β-amino ester) (PBAE) co-polymers (PEG-PBAE) and blends of PEG-PBAEs and PBAEs and their use for delivering drugs, genes, and other pharmaceutical or therapeutic agents safely and effectively to different sites in the body and to different cells, such as cancer cells, are disclosed.</p>
>> Read More

TUMOR BIOMARKERS AND USE THEREOF (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">Disclosed herein are biomarkers related to WNT signal transduction pathway, as well as methods and kits comprising the same. Further, the present disclosure relates to the use of the biomarkers in patient selection, companion diagnostics, and treatment of cancer.</p>
>> Read More

METHODS USING HDAC11 INHIBITORS (Fri, 27 Apr 2018)
The present invention provides methods and uses of inhibitors of histone deacetylase 11 (HDAC11) in the treatment of diseases and/or disorders, such as, for example, cell proliferative diseases.
>> Read More

POLYMORPHIC FORMS OF PALBOCICLIB (Fri, 27 Apr 2018)
The present invention relates to polymorphic forms of palbociclib and processes for preparation thereof,to pharmaceutical compositions comprising palbociclib,and to the use of such compositions for the treatment of cancer.
>> Read More

PHARMACEUTICAL COMPOUNDS (Fri, 27 Apr 2018)
A compound which is an arylimidazolyl isoxazole of formula (I): (Formula (I)) or a pharmaceutically acceptable salt thereof. The compound has activity in modulating the activity of p300 and/or CBP and is used to treat cancer, particularly prostate cancer.
>> Read More

PHARMACEUTICAL COMPOUNDS (Fri, 27 Apr 2018)
A compound which is a benzimidazole of formula (I): wherein X is a 5-membered heteroaryl group selected from the following: or a pharmaceutically acceptable salt thereof. The compound has activity in modulating the activity of p300 and/or CBP and is used to treat cancer, particularly prostate cancer.
>> Read More

COMPOUNDS AND METHODS TO SENSITIZE CANCER CELLS TO TYROSINE KINASE INHIBITORS (Fri, 27 Apr 2018)
The present invention generally relates to sensitizer compounds and their use in combination with Tyrosine Kinase Inhibitors (TKIs) for sensitizing tumor, cancer or pre-cancerous cells to TKI treatment. In particular, the present invention relates to administration regimes that combine TKIs such as Gefitinib or Icotinib with TKI- sensitizing DZ1 esters and amides conjugated to statin or platin-based drugs, or to Artemisinin, including, without limitation: DZl-Simvastatin amide, DZl-Simvastatin ester, DZl-Cisplatin ester, and DZl-Cisplatin amide, DZl-Artemisinin ester, and DZl-Artemisinin amide. Furthermore, the present invention relates to improved TKI treatment of cancers by sensitizing tumor, cancer or pre-cancerous cells, in particular cancers that develop TKI resistance, including e.g. lung cancer and pancreatic cancer.
>> Read More

URINARY POLYAMINES AS PROSTATE CANCER DETECTION BIOMARKERS (Fri, 27 Apr 2018)
Privided is a novel, highly-sensitive and specific, method for detecting and quantifying urinary polyamines using lanthanide complexes or DNA capped gold nanoparticles.
>> Read More

TARGETED DELIVERY OF NICOTINAMIDE ADENINE DINUCLEOTIDE SALVAGE PATHWAY INHIBITORS (Fri, 27 Apr 2018)
Compounds and compositions are disclosed in which a NAMPT Drug Unit is linked to a targeting Ligand Unit through a Unit from which a NAMPT inhibitor compound or derivative thereof 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

PYRIMIDO-DIAZEPINONE KINASE SCAFFOLD COMPOUNDS AND METHODS OF TREATING DCLK1/2-MEDIATED DISORDERS (Fri, 27 Apr 2018)
The present invention relates to use of pyrimido-diazepinone compounds that are able to modulate protein kinases such as doublecortin-like kinase (DCLK1) and doublecortin-like kinase 2 (DCLK2), which are members of serine/threonine-protein kinase family and Ca2+/calmodulin-dependent protein kinase class of enzymes, and the use of such compounds in the treatment of various diseases, disorders or conditions.
>> Read More

BROMODOMAIN INHIBITOR (Fri, 27 Apr 2018)
Described herein is the bromodomain inhibitor 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one, including crystalline forms, amorphous forms, solvates, and hydrates thereof, as well as pharmaceutical compositions that include this bromodomain inhibitor. In some embodiments the pharmaceutical composition comprises 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one that has been processed by micronization or spray dried dispersion. In some embodiments, the pharmaceutical composition further comprises at least one polymer. In some embodiments, the pharmaceutical compositions comprises a solid polymer matrix comprising 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one and at least one polymer. Pharmaceutical compositions comprising 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one are useful for the treatment of cancer or neoplastic disease.
>> Read More

CONDENSED BENZODIAZEPINE DERIVATIVES AND CONJUGATES MADE THEREFROM (Fri, 27 Apr 2018)
A compound capable of inhibiting cell proliferation, having a structure according to formula (I) wherein the variables in formula (I) are as defined in the specification. Such compounds are useful as anti-cancer agents, especially in antibody-drug conjugates.
>> Read More

PHENOTHIAZINE DERIVATIVES AND METHODS OF USE THEREOF (Fri, 27 Apr 2018)
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.
>> Read More

COMPOUNDS AND METHODS TO SENSITIZE CANCER CELLS TO CISPLATIN (Fri, 27 Apr 2018)
The present invention generally relates to sensitizer compounds and their use to sensitize cancer and/or pre-cancerous cells of certain cancers to treatment with certain resistance-prone therapeutics used in cancer therapy. In embodiments, the conjugates of particular esters or amides of Near Infrared Dyes, are used as sensitizers to avoid or overcome therapeutic resistance once formed. In embodiments, the sensitizers include conjugates with Cisplatin, Simvastatin, Artemisinin, platin-based compounds or statins. In embodiments, the resistance prone cancer therapeutics include cisplatin, gemcitabine, doxorubicin, paclitaxel, docetaxel, and platin-based compounds. These may be administered in combination with the sensitizer, or the sensitizer itself may comprise an therapeutci-derived moiety conjugated to the sensitizer, for example as is the case for dye-CIS conjugated sensitizers. Alternatively, the sensitizer may be co-administered with one or more therapeutic.
>> Read More

HETEROARYL DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING DISEASES ASSOCIATED WITH PI3 KINASES, CONTAINING SAME AS ACTIVE INGREDIENT (Thu, 26 Apr 2018)
The present invention relates to a heteroaryl derivative or a pharmaceutically acceptable salt thereof, a preparation method therefor, and a pharmaceutical composition for preventing or treating diseases associated with PI3 kinases, containing the same as an active ingredient. The heteroaryl derivative according to the present invention has an excellent effect of selectively inhibiting PI3 kinases, thereby being useful in preventing or treating PI3 kinase diseases such as: cancers such as hematologic malignancy, ovarian cancer, uterine cervical cancer, breast cancer, colorectal cancer, liver cancer, gastric cancer, pancreatic cancer, colon cancer, peritoneal metastatic cancer, skin cancer, bladder cancer, prostate cancer, lung cancer, osteosarcoma, fibrous tumors, and brain tumors; autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosis, multiple sclerosis, diabetes mellitus, hyperthyroidism, myasthenia, Crohn's disease, ankylosing spondylitis, autoimmune pernicious anemia, and Sjogren's syndrome; and respiratory diseases such as chronic obstructive pulmonary disease (COPD), rhinitis, asthma, chronic bronchitis, chronic pulmonary inflammatory diseases, silicosis, pulmonary sarcoidosis, pleurisy, alveolitis, angitis, pneumatosis, pneumonia, and bronchiectasis.
>> Read More

TRICYCLIC DERIVATIVE COMPOUND, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION COMPRISING SAME (Thu, 26 Apr 2018)
The present invention relates to novel tricyclic derivative compounds, and more specifically to tricyclic derivative compounds, optical isomers thereof, racemates thereof, or pharmaceutically acceptable salts thereof, which have excellent activity against PARP-1, tankyrase-1 or tankyrase-2. The tricyclic derivative compounds, optical isomers thereof, racemates thereof or pharmaceutically acceptable salts thereof according to the present invention have inhibitory activity against PARP-1, tankyrase-1, or tankyrase-2, and thus can be effectively used for the prevention or treatment of neuropathic pain, neurodegenerative diseases, cardiovascular diseases, diabetic neuropathy, inflammatory diseases, osteoporosis, or cancer.
>> Read More

APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES (Thu, 26 Apr 2018)
Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein.
>> Read More

PIPERIDINE DERIVATIVE AND PREPARATION METHOD AND PHARMACEUTICAL USE THEREOF (Thu, 26 Apr 2018)
The present invention relates to a piperidine derivative and the preparation method and a pharmaceutical use thereof. In particular, the present invention relates to the piperidine derivative as shown by general formula (I) and the preparation method thereof and a pharmaceutical composition containing same, and the use thereof as an estrogen receptor modulator in the treatment of estrogen receptor mediated or dependent diseases or conditions, the diseases particularly preferably being breast cancer. In the abstract, the definition of each substituent of the general formula (I) is the same as that in the description.
>> Read More

COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE FOR THE TREATMENT OF CANCER (Thu, 26 Apr 2018)
The present invention relates to compounds useful as inhibitors of ATR protein kinase for use in the treatment of a cancer having a defect in the ATM signaling pathway. The disclosure also relates to pharmaceutically acceptable compositions comprising the compounds of this invention and combination therapies thereof; use of said compounds in the treatment of various diseases, disorders, and conditions; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: wherein the variables are as defined herein. Preferably, the compound is VE-822.
>> Read More

1,4-DI-SUBSTITUTED IMIDAZOLE DERIVATIVE (Thu, 26 Apr 2018)
The present invention provides a 1,4-disubstituted imidazole derivative of formula (1') wherein ring Q 1 is optionally-substituted C 6-10 aryl group, etc.; R 1 and R 2 are independently hydrogen atom, etc.; W 1 is optionally-substituted C 1-4 alkylene group; W 2 is -NR 3a C(O)- wherein R 3a is hydrogen atom or C 1-6 alkyl group, etc.; ring Q 2 is 5- to 10-membered heteroaryl group, etc.; W 3 is optionally-substituted C 1-4 alkylene group, etc.; n is 1, 2, 3, 4, or 5; R 4 is independently halogen atom, optionally-substituted C 1-6 alkyl group, etc.; R 5 is hydroxy group, etc.; and a pharmacologically acceptable salt thereof, which have a potent inhibitory effect on the sphere-forming capacity of cancer cells and are useful as an orally-available anti-tumor agent.
>> Read More

BRK INHIBITORY COMPOUND (Thu, 26 Apr 2018)
The present invention relates to a compound represented by general formula (I) (wherein, all symbols represent the same meanings as the symbols set forth in the specification), a salt thereof, a solvate thereof, an N-oxide thereof, or a prodrug of any of these. Since the compound has a Brk inhibitory activity, the compound is useful as a drug ingredient for the prevention and/or treatment of Brk-related diseases such as cancer, for example.
>> Read More

''''SYNTHESIS AND STUDIES OF SOME NOVELS-TRIAZINE BASED ISOXAZOLE FROM CYANURIC CHLORIDE'''' (Sat, 21 Apr 2018)
The present invention relates to synthesis and studies of some novel 2,4?6-tri-substituted-l,3,5-triazine containing isoxazole by sequential substitution of the three chlorides of cyanuric chloride by one oxygen and two nitrogens centered nucleophiles by substituting parachloro benzaldehyde oxime, aniline and sulphacetamide sodium. The compound (1) obtained were further treated with various aldehydes such as furfuraldehyde (la), Dimethylaminobenzaldehyde (lb), parachloro benzaldehyde (lc) and vanillin (Id). All the synthesized compounds on cyclization with hydroxylamine hydrochloride in the presence of alkali to give isoxazole ring substituted 2,4, 6-tri-substituted-l,3,5-triazine compounds (2a-2d). All the products obtained from these reactions are characterized by elemental analysis, IR, "H-NMR, l3C-NMR, Mass spectra, molecular properties, docking and in-vitro studies for anti-cancer and anti-microbial activity.
>> Read More

4-(2-AMINO-TETRAHYDRONAPHTHALENYL)PYRIMIDINE DERIVATIVE, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING CANCER, CONTAINING SAME AS ACTIVE INGREDIENT (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">The present invention relates to a 4-(2-amino-tetrahydronaphthaleneyl)pyrimidine derivative, a preparation method thereof, and a pharmaceutical composition for the prevention or treatment of cancer comprising the same as an active ingredient. The 4-(2-amino-tetrahydronaphthaleneyl)pyrimidine derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention is very effective in suppressing anaplastic lymphoma kinase (ALK) activity and as a result it can improve the effectiveness of treatment on cancer cells having anaplastic lymphoma kinase (ALK) fusion proteins such as EML4-ALK and NPM-ALK, so that it can be effectively used as a pharmaceutical composition for preventing or treating cancer.</p>
>> Read More

PYRROLOPYRIMIDINE COMPOUNDS FOR THE TREATMENT OF CANCER (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">Compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="26.50mm" wi="55.46mm" file="US20180104247A1-20180419-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein: one of X and X′ is N and the other of X and X′ is C, are described, along with compositions containing the same and methods of use thereof in the treatment of cancer.</p>
>> Read More

Nanoparticles, Composed of Sterol and Saponin From Quillaja Saponaria Molina Process for Preparation and Use Thereof as Carrier for Amphipatic of Hydrophobic Molecules in Fields of Medicine Including Cancer Treatment and Food Related Compounds (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">A nanoparticle comprising at least one sterol, e.g. cholesterol and a component from Quillaja Saponaria Molina (QuilQ) selected from quillaja saponin, characterized in that said nanoparticles do not comprise a phospholipid and in that the sterol molecule is bound by a hydrophobic bond between a hydroxyl group of the sterol and terpene moieties in a Quil A micelle and by an hydrophilic ester bond between a sterol OH<sup>−</sup> and COOH<sup>−</sup> or aldehyde groups in the QuilA micelle. It also relates to a composition comprising the nanoparticles, and the use thereof as carriers for amphipathic or hydrophobic molecules and as agents for treatment of cancer. Further, it regards a method for producing the phospholipid-free nanoparticles, a method for the treatment of cancer and a method for assessing the applicability of the cancer treating method.</p>
>> Read More

RADIOTRACER DERIVATIVES OF TRIMETHOPRIM FOR DIAGNOSITC IMAGING (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">The present invention provides radiolabeled trimethoprim which are useful in imaging tests such as PET scans. The compounds show robust bacterial uptake in vitro and identify infections from inflammation or tumor when administered to a subject. The compounds show rapid and sensitive detection of Ec DHFR containing tumors from control tumors and background tissue. In one aspect, a compound having the structure of formula (I) is provided or a pharmaceutically acceptable salt or prodrug thereof, wherein R is defined herein. Also provided are compositions containing these compounds, positron emission tomography reporter probe comprising these compounds, and methods of imaging a bacterial infection, tracking or monitoring bacteria, distinguishing a bacterial infection from inflammation or tumor, monitoring genetically fused protein expression, and monitoring genetically engineered cells in clinical scenarios such as immunotherapy for cancer treatment.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.86mm" wi="63.33mm" file="US20180104365A1-20180419-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

PYRIDYL BENZOTHIOPHENES AS KINASE INHIBITORS (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">This invention is directed to compounds, which are useful as protein kinase (PK) inhibitors and can be used to treat such diseases as cancer, blood vessel proliferative disorders, fibrotic disorders, mesangial cell proliferative disorders, metabolic diseases inflammatory disorders and neurodegenerative disorders.</p>
>> Read More

TRKA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">The present invention is directed to bicyclic heteroaryl benzamide compounds of formulas (I): which are tropomyos-in-related kinase (Trk) family protein kinase inhibitors, and hence are useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.</p>
>> Read More

PREPARATION AND USE OF NOVEL PROTEIN KINASE INHIBITORS (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">The invention provides novel compounds and methods of using such compounds to treat or prevent cancer.</p>
>> Read More

NOVEL CYCLOSPORIN DERIVATIVES AND USES THEREOF (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">The present invention relates to a compound of the Formula (I)):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="44.11mm" wi="75.69mm" file="US20180105558A1-20180419-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same, a method for treating or preventing viral infections, inflammation, dry eye, central nervous disorders, cardiovascular diseases, cancer, obesity, diabetes, muscular dystrophy, and hair loss.</p>
>> Read More

Biologically Active Taxane Analogs and Methods of Treatment by Oral Administration (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">The present invention relates to a novel chemical compound for use in the treatment of cancer, to compositions containing said compound, methods of manufacture and combinations with other therapeutic agents.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="47.33mm" wi="75.44mm" file="US20180105535A1-20180419-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

CYTIDINE DERIVATIVE DIMERS AND APPLICATIONS THEREOF (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">The present disclosure provides cytidine derivative dimers, salts and compositions of the cytidine derivative dimers, and methods of making and using the cytidine derivative dimers that are useful for treating a neoplasm in mammalian subjects. A cytidine derivative dimer may have the following general formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="85.17mm" wi="76.20mm" file="US20180105550A1-20180419-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">By molecularly designing such cytidine-based compounds, the disclosed cytidine-based derivative dimers/salts show significant inhibiting effects on HCT-116 human colon cancer cells, and exhibit strong growth inhibiting effects on HCT-116 human colon cancer xenografts grown in nude mice. The disclosed cytidine derivative dimers/salts provide high anti-tumor activity with low toxicity and are useful for treating cancers.</p>
>> Read More

N1-CYCLIC AMINE-N5-SUBSTITUTED BIGUANIDE DERIVATIVES, METHODS OF PREPARING THE SAME AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">The present invention provides an N1-cyclic amine-N5-substituted biguanide derivative compound represented by Formula 1, a method of preparing the same and a pharmaceutical composition including the biguanide derivative or the pharmaceutically acceptable salt thereof as an active ingredient. The biguanide derivatives have an effect of inhibiting cancer cell proliferation, cancer metastasis and cancer recurrence by activation of AMPK, even when administered in a small dose compared with conventional drugs.</p>
>> Read More

GLUTATHIONE-CLEAVABLE PRODRUG AND METHODS OF USE THEREOF (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">A glutathione-cleavable prodrug is provided herein, as well as methods for its use in treating cancer, including triple negative breast cancer. The prodrug can be cleaved by glutathione under physiological conditions to generate a biologically active agent. The compound described herein is advantageous as the compound is fluorescent and can therefore be monitored within a subject.</p>
>> Read More

INHIBITORS OF PHOSPHOGLYCERATE DEHYDROGENASE (PHGDH) AND USES THEREOF (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">The present invention provides compounds pounds of Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, pro-drugs, and compositions thereof. Also provided are methods and kits involving the compounds of Formula (I), (II) or (III) for treating diseases associated with the over-expression of phosphoglycerate dehydrogenase (PHGDH) in a subject, such as proliferative diseases (e.g., cancers (e.g., breast cancer, ER negative breast cancer, melanoma, cervical cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases). Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the activity of PHGDH or inhibit the serine biosynthetic pathway, or both.</p>
>> Read More

ISOXAZOLYL SUBSTITUTED IMIDAZOPYRIDINES (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">A compound which is an isoxazolyl imidazopyridine of formula (I): wherein: R<sup>0 </sup>and R, which are the same or different, are each H or C alkyl; R<sup>9′</sup> and R<sup>9″</sup>, which are the same or different, are each H or F; X is -(alk)<sub>n</sub>-, -alk-C(═O)—NR—, -alk-NR—C(═O)— or -alk-C(═O)—; R<sup>1 </sup>is selected from —S(═O)<sub>2</sub>R′ and a 4- to 7-membered heterocyclic group which is unsubstituted or substituted; R<sup>2 </sup>and R<sup>2′</sup>, which are the same or different, are each H or C<sub>1-6 </sub>alkyl; or R<sup>2 </sup>and R<sup>2′</sup> form, together with the C atom to which they are attached, a C<sub>3-6 </sub>cycloalkyl group; R<sup>3 </sup>and R<sup>3′</sup>, which are the same or different, are each H, C<sub>1-6 </sub>alkyl, OH or F; R<sup>4 </sup>is phenyl or a 5- to 12-membered N-containing heteroaryl group and is unsubstituted or substituted; alk is C<sub>1-6 </sub>alkylene; R′ is C<sub>1-6 </sub>alkyl; and n is 0 or 1; or a pharmaceutically acceptable salt thereof. The compound has activity in modulating the activity of p300 and/or CBP and is used to treat cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.61mm" wi="63.67mm" file="US20180105519A1-20180419-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

HISTONE DEMETHYLASE INHIBITORS (Fri, 20 Apr 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 pyrrolopyridine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of histone demethylase. 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

BICYCLIC AND TRICYCLIC PYRIMIDINE TYROSINE KINASE INHIBITORS WITH ANTITUBULIN ACTIVITY AND METHODS OF TREATING A PATIENT (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">Bicyclic and tricyclic pyrimidine tyrosine kinase inhibitors with antitubulin activity are provided in the present invention. The compositions of the present invention possess dual activity in a single agent of potent vascular endothelial growth factor receptor inhibitory activity as well as antitubulin activity. Water soluble salts of these compositions are also described. Methods of treating a patient having cancer, macular degeneration, and arthritis with the compositions and salts thereof of the present invention are disclosed.</p>
>> Read More

HETEROCYCLIC COMPOUNDS AND THEIR USES (Fri, 20 Apr 2018)
<p id="p-0001" num="0000">Substituted bicyclic heteroaryls and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiples sclerosis, Sjoegren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity, The present invention also enables methods for treating cancers that are mediated, dependent on or associated with p110δ activity, including but not restricted to leukemias, such as Acute Myeloid leukaemia (AML) Myelo-dysplastic syndrome (MDS) myelo-proliferative diseases (MPD) Chronic Myeloid Leukemia (CML) T-cell Acute Lymphoblastic leukaemia (T-ALL) B-cell Acute Lymphoblastic leukaemia (B-ALL) Non Hodgkins Lymphoma (NHL) B-cell lymphoma and solid tumors, such as breast cancer.</p>
>> Read More

ULTRALOW-POWER NEAR INFRARED LAMP LIGHT OPERABLE TARGETED ORGANIC NANOPARTICLE PHOTODYNAMIC THERAPY (Fri, 20 Apr 2018)
The invention provides a novel class of NIR-absorbing biocompatible organic nanoparticles for effective imaging, targeting and treatment of deep-tissue cancers or tumors. The invention enables a new platform for precise cancer- or tumor-targeting theranostics and clinical cancer treatment.
>> Read More

INHIBITORS OF MUTANT ISOCITRATE DEHYDROGENASES AND COMPOSITIONS AND METHODS THEREOF (Fri, 20 Apr 2018)
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.
>> Read More

BROMODOMAIN INHIBITORS (Fri, 20 Apr 2018)
Provided are compounds of formula (I),wherein R 1, Y, X 1, X 2, R 2, R 3, R 4, R 5, R 6 and m have any of the values defined in the specification and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising compounds of formula (I).
>> Read More

BROMODOMAIN INHIBITORS (Fri, 20 Apr 2018)
Provided herein are compounds of formula (I) wherein R 1, Y, L 1, G 1, X 1, X 2, L 2, R 2, R 3, and R 4 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, which are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising compounds of formula (I).
>> Read More

CYCLOHEPTAPEPTIDE AGENTS FOR TREATMENT OF CANCER AND OBESITY DISEASES (Fri, 20 Apr 2018)
New anticancer and anti-obesity agents based on the cyclic peptide compounds are disclosed, and its preparation and application method for treating cancer and obesity diseases are also disclosed.
>> Read More

BENZOTHIAZOLE DERIVATIVES AS DYRK1 INHIBITORS (Fri, 20 Apr 2018)
The present invention relates to compounds of Formula (I), which are DYRK1A and/or DYRK1B inhibitors,and their use in the treatment of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), metabolic disorders such as Metabolic Syndrome or diabetes mellitus, and cancer.
>> Read More

CRYSTALLINE FORMS OF 4-(2-((1R,2R)-2-HYDROXYCYCLOHEXYLAMINO) BENZOTHIAZOL-6-YLOXY)-N-METHYLPICOLINAMIDE (Fri, 20 Apr 2018)
This application relates to various crystalline forms of 4-(2-((1R,2R)-2-hydroxycyclohexylamino)benzothiazol-6-yloxy)-N-methylpicolinamide hydrochloride salts as well as compositions and methods of using the same. In some embodiments the crystalline forms also contain water ("hydrates"). These materials are useful in the treatment of various diseases, including glioblastoma multiforme, breast cancer, pancreatic cancer and other solid tumors.
>> Read More

HISTONE DEACETYLASE INHIBITORS AND USES THEREOF (Fri, 20 Apr 2018)
Provided herein are compounds of the formula (I) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of cancer.
>> Read More

LIPIDATED IMMUNE RESPONSE MODIFIER COMPOUND COMPOSITIONS, FORMULATIONS, AND METHODS (Fri, 20 Apr 2018)
The compound N-(4- { [4-amino-2-butyl- 1H-imidazo [4,5-c] quinolin- lyl] oxy} butyl)octadecanamide is a useful drug compound for enhancing immune response and can be used, for example, as a vaccine adjuvant and a cancer treatment.
>> Read More

TUMOR AND MICROENVIRONMENT GENE EXPRESSION, COMPOSITIONS OF MATTER AND METHODS OF USE THEREOF (Fri, 13 Apr 2018)
<p id="p-0001" num="0000">This invention relates generally to compositions and methods for identifying genes and gene networks that respond to, modulate, control or otherwise influence tumors and tissues, including cells and cell types of the tumors and tissues, and malignant, microenvironmental, or immunologic states of the tumor cells and tissues. The invention also relates to methods of diagnosing, prognosing and/or staging of tumors, tissues and cells, and provides compositions and methods of modulating expression of genes and gene networks of tumors, tissues and cells, as well as methods of identifying, designing and selecting appropriate treatment regimens. The invention also relates to the modulation of complement activity to shift cellular immunity and obtain an effective therapeutic response.</p>
>> Read More

3-(1H-BENZIMIDAZOL-2-YL)-1H-PYRIDIN-2-ONE DERIVATIVES (Fri, 13 Apr 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="24.21mm" wi="69.85mm" file="US20180099947A1-20180412-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which W, R<sup>1</sup>, R<sup>2 </sup>and R<sup>3 </sup>have the meanings indicated in claim <b>1,</b> are inhibitors of ALK1, AL2 and ALK5, and can be employed for the treatment of diseases such as cancer.</p>
>> Read More

Compounds Useful for Inhibiting Metastasis from Cancer and Methods Using Same (Fri, 13 Apr 2018)
<p id="p-0001" num="0000">The present invention includes compositions that are useful in preventing or treating metastasis in a subject diagnosed with cancer. The present invention also includes methods of preventing or treating metastasis in a subject diagnosed with cancer, wherein the method comprises administering to the subject in need thereof an effective amount of a pharmaceutical formulation comprising at least one pharmaceutically acceptable carrier and at least one CX<sub>3</sub>CR1 or fractalkine antagonist.</p>
>> Read More

NOVEL COMPOUNDS AS REARRANGED DURING TRANSFECTION (RET) INHIBITORS (Fri, 13 Apr 2018)
<p id="p-0001" num="0000">This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.</p>
>> Read More

VACCINE COMPOSITIONS AND METHODS OF USE THEREOF (Fri, 13 Apr 2018)
<p id="p-0001" num="0000">Nanoparticle-based vaccines, compositions, kits and methods are used for the effective delivery of one or more antigens in vivo for vaccination and antibody (e.g., monoclonal antibody) production, and for the effective delivery of peptides, proteins, siRNA, RNA or DNA to PAPCs or MHC class II positive cells (e.g. tumor cells). Antigens may be, for example, DNA that results in expression of the gene of interest and induction of a robust and specific immune response to the expressed protein in a subject (e.g., mammal). Antigens may also be immunogenic peptides or polypeptides that are processed and presented. In one embodiment, a nanoparticle-based method to deliver antigens in vivo as described herein includes injection of a vaccine composed of a DNA encoding at least one antigen, or at least one antigenic peptide or polypeptide conjugated to a charged dendrimer (e.g., PADRE-derivatized dendrimer) that is also conjugated to a T helper epitope (e.g., PADRE). Negatively-charged plasmids bind naturally to a positively-charged PADRE-dendrimer, while peptide or polypeptide antigens can be chemically linked to the PADRE-dendrimer if they are not negatively-charged. Alternatively, negatively-charged dendrimers may be used. The compositions, kits, vaccines and methods described herein have both prophylactic and treatment applications, i.e., can be used as a prophylactic to prevent onset of a disease or condition in a subject, as well as to treat a subject having a disease or condition. A vaccine as described herein can be used to mount an immune response against any infectious pathogen or cancer.</p>
>> Read More

Quinazoline Derivatives as VEGF Inhibitors (Fri, 13 Apr 2018)
<p id="p-0001" num="0000">The invention relates to quinazoline derivatives of formula (I), wherein m is an integer from 1 to 3; R<sup>1 </sup>represents halogeno or C<sub>1-3</sub>alkyl; X<sup>1 </sup>represents —O—; R<sup>2 </sup>is selected from one of the following three groups: 1) C<sub>1-5</sub>alkylR<sup>3 </sup>(wherein R<sup>3 </sup>is piperidin-4-yl which may bear one or two substituents selected from hydroxy, halogeno, C<sub>1-4 </sub>alkyl, C<sub>1-4</sub>hydroxyalkyl and C<sub>1-4</sub>alkoxy; 2) C<sub>2-5</sub>alkenylR<sup>3 </sup>(wherein R<sup>3 </sup>is as defined hereinbefore); 3) C<sub>2-5</sub>alkynylR<sup>3 </sup>(wherein R<sup>3 </sup>is as defined hereinbefore); and wherein any alkyl, alkenyl or alkynyl group may bear one or more substituents selected from hydroxy, halogeno and amino; and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.17mm" wi="69.85mm" file="US20180099946A1-20180412-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Macroheterocyclic nucleoside derivatives and their analogues, production and use thereof (Fri, 13 Apr 2018)
<p id="p-0001" num="0000">Nucleosides and nucleotides (nucleos(t)ides) have been in clinical use for almost 50 years and have become cornerstones of treatment for patients with viral infections or cancer. The approval of several additional drugs over the past decade demonstrates that this family still possesses strong potential. Therefore nucleos(t)ide are of great interest as promising chemotherapeutic agents, including: 2′-deoxy-L-uridine (CAS No 31501-19-6), 2′-deoxy-D-uridine (CAS No 951-78-0), telbivudine (CAS No 3424-98-4), zidovudine (AZT, CAS No 30516-87-1), trifluridine (CAS No 70-00-8), clevudine (CAS No 163252-36-6), PSI-6206 (CAS No 863329-66-2), 2′-(5)-2′-chloro-2′-deoxy-2′-fluorouridine (CAS No 1673560-41-2), ND06954 (CAS No 114248-23-6), stavudine (CAS No 3056-17-5), 5-ethynyltavudine (Festinavir, CAS No 634907-30-5), torcitabine (CAS No 40093-94-5), (−)-beta-D-(2R,4R)-dioxolane-thymine (DOT, 1-((2R,4R)-2-(hydroxymethyl)-1,3-dioxolan-4-yl)-5-methyl-2,4 (1H,3H)-pyrimidinedione, CAS No. 127658-07-5), 2-(6-amino-purin-9-yl)-ethanol (CAS No 707-99-3), 2′-C-methylcytidine (CAS No 20724-73-6), PSI-6130 (CAS No 817204-33-4), gemcitabine (CAS No 95058-81-4), 2′-chloro-2′-deoxy-2′-fluorocytidine (CAS No 1786426-19-4), 2′,2′-dichloro-2′-deoxycytidine (CAS No 1703785-65-2), 2′-C-methylcytidine (CAS No 20724-73-6), PSI-6130 (CAS No 817204-33-4), lamivudine (3TC, CAS No 134678-17-4), emtricitabine (CAS No 143491-57-0), 2′-deoxyadenosine (CAS No 958-09-8), 2′-deoxy-β-L-adenosine (CAS No 14365-45-8), 2′-deoxy-4′-C-ethynyl-2-fluoroadenosine (CAS No 865363-93-5), didanosine (CAS No 69655-05-6), entecavir (CAS No 209216-23-9), FMCA (CAS No 1307273-70-6), dioxolane-G (DOG, CAS No 145514-01-8), β-D-2′-deoxy-2′-(R)-fluoro-2′-β-C-methylguanosine (CAS No 817204-45-8), abacavir (ABC, CAS No 136470-78-5), dioxolane-A (DOA, CAS #145514-02-9), [(2R,4R)-4-(6-cyclopropylamino-purin-9-yl)-[1,3]dioxolan-2-yl]-methanol (CAS No 1446751-04-7), amdoxovir (AMDX, CAS No 145514-04-1), (R)-1-(6-amino-purin-9-yl)-propan-2-ol (CAS No 14047-28-0), and [(2S,5R)-5-(6-amino-purin-9-yl)-4-fluoro-2,5-dihydro-furan-2-yl]-methanol.</p> <p id="p-0002" num="0000">Macroheterocyclic nucleoside derivative and its analogue of the general formula 1 or general formula 2, 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="86.02mm" wi="71.54mm" file="US20180099989A1-20180412-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">wherein: <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000">Ar is aryl or hetaryl;</li> <li id="ul0001-0002" num="0000">R<sup>1 </sup>and R<sup>2 </sup>are not necessarily the same substituents selected from H, F, Cl, CH<sub>3</sub>, OH;</li> <li id="ul0001-0003" num="0000">R<sub>3 </sub>is H or CH<sub>3</sub>;</li> <li id="ul0001-0004" num="0000">X is oxygen or ethanediyl-1,1 (C═CH<sub>2</sub>);</li> <li id="ul0001-0005" num="0000">Y is CH(R<sup>4</sup>)(CH<sub>2</sub>)<sub>k</sub>, CH(R<sup>4</sup>)(CH<sub>2</sub>)<sub>m</sub>C(O)O(CH<sub>2</sub>)<sub>n</sub>;</li> <li id="ul0001-0006" num="0000">R<sup>4 </sup>is H or CH<sub>3</sub>;</li> <li id="ul0001-0007" num="0000">k has a value from zero to six;</li> <li id="ul0001-0008" num="0000">m has a value from zero to two;</li> <li id="ul0001-0009" num="0000">n has a value of one to four;</li> <li id="ul0001-0010" num="0000">Q is a radical selected from Q1-Q4;</li> </ul> </p> <p id="p-0005" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="107.61mm" wi="54.02mm" file="US20180099989A1-20180412-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0006" num="0000">wherein: R<sup>5 </sup>is the substituent selected from H, F, Cl, CH<sub>3</sub>, OH; <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">the arrow (→) indicates the location, joined by Q1-Q4.</li> </ul> </p>
>> Read More

BIFUNCTIONAL STAPLED POLYPEPTIDES AND USES THEREOF (Fri, 13 Apr 2018)
<p id="p-0001" num="0000">The invention relates to bifunctional stapled or stiched peptides comprising a targeting domain, a linker moiety, and an effector domain, that can be used to tether, or to bring into close proximity, at least two cellular entities (e.g., proteins). Certain aspects relate to bifunctional stapled or stiched peptides that bind to an effector biomolecule through the effector domain and bind to a target biomolecule through the targeting domain. Polypeptides and/or polypeptide complexes that are tethered by the bifunctional stapled or stiched peptides of the invention, where the effector polypeptide bound to the effector domain of the bifunctional stapled or stiched peptide modifies or alters the target polypeptide bound to the targeting domain of the bifunctional peptide. Usesses of the inventive bifunctional stapled or stiched peptides including methods for treatment of disease (e.g., cancer, inflammatory diseases) are also provided.</p>
>> Read More

NOVEL ARYL-CYANOGUANIDINE COMPOUNDS (Fri, 13 Apr 2018)
<p id="p-0001" num="0000">The present invention relates to protein-lysine N-methyltransferase SMYD2 (SET and MYND domain-containing protein 2) inhibitors, in particular SMYD2-inhibitory substituted cyanoguanidine- pyrazolines of general formula (I), wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and R<sup>5 </sup>have the meaning as described and defined herein, as well as to pharmaceutical compositions comprising compounds according to the invention and to their prophylactic and therapeutic use for hyperproliferative disorders, in particular for cancer, respectively tumour disorders. The present invention furthermore relates to the use of SMYD2 inhibitors for benign hyperplasias, atherosclerotic disorders, sepsis, autoimmune disorders, vascular disorders, viral infections, neurodegenerative disorders, inflammatory disorders, atherosclerotic disorders and the control of male fertility.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="52.83mm" wi="66.12mm" file="US20180099937A1-20180412-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

SPIROCYCLIC COMPOUNDS (Fri, 13 Apr 2018)
Disclosed herein are spirocyclic compounds, together with pharmaceutical compositions and methods of ameliorating and/or treating a cancer described herein with one or more of the compounds described herein.
>> Read More

MODULATION OF NOVEL IMMUNE CHECKPOINT TARGETS (Fri, 13 Apr 2018)
Dysfunctional or exhausted T cells arise in chronic diseases including chronic viral infections and cancer, and express high levels of co-inhibitory receptors. Therapeutic blockade of these receptors has clinical efficacy in the treatment of cancer. While co- inhibitory receptors are co-expressed, the triggers that induce them and the transcriptional regulators that drive their co-expression have not been identified. The immunoregulatory cytokine IL-27 induces a gene module in T cells that includes several known co-inhibitory receptors (Tim-3, Lag-3, and TIGIT). The present invention provides a novel immunoregulatory network and novel cell surface molecules that have an inhibitory function in the tumor microenvironment. The present invention further provides the novel discovery that the transcription factors Prdml and c-Maf cooperatively regulate the expression of the co-inhibitory receptor module. This critical molecular circuit underlies the expression of co- inhibitory receptors such as ILT-3 in dysfunctional T cells and identifies novel regulators of T cell dysfunction.
>> Read More

CHIMERIC ANTIGEN RECEPTORS FOR THE TREATMENT OF CANCER (Fri, 13 Apr 2018)
The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.
>> Read More

HETEROCYCLIC COMPOUNDS AS INHIBITORS OF RAS AND METHODS OF USE THEREOF (Fri, 13 Apr 2018)
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein A, B, R", Q, W, X, Y, Z, n1, n2and '--" are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also disclosed.
>> Read More

INHIBITORS OF GLUCOCORTICOID RECEPTOR (Fri, 13 Apr 2018)
The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer.
>> Read More

THERAPEUTIC AND DIAGNOSTIC METHODS FOR CANCER (Fri, 13 Apr 2018)
The present invention provides therapeutic and diagnostic methods and compositions for cancer, for example, lung cancer (e.g., NSCLC), bladder cancer (e.g., UC), kidney cancer (e.g., RCC), breast cancer (e.g., TNBC), or melanoma. The invention provides methods of treating cancer (e.g., lung cancer (e.g., NSCLC), bladder cancer (e.g., UC), kidney cancer (e.g., RCC), breast cancer (e.g., TNBC), or melanoma), methods of determining whether a patient suffering from cancer (e.g., lung cancer (e.g., NSCLC), bladder cancer (e.g., UC), kidney cancer (e.g., RCC), breast cancer (e.g., TNBC), or melanoma) is likely to respond to treatment comprising a PD-L1 axis binding antagonist, methods of predicting responsiveness of a patient suffering from cancer (e.g., lung cancer (e.g., NSCLC), bladder cancer (e.g., UC), kidney cancer (e.g., RCC), breast cancer (e.g., TNBC), or melanoma) to treatment comprising a PD-L1 axis binding antagonist, and methods of selecting a therapy for a patient suffering from cancer (e.g., lung cancer (e.g., NSCLC), bladder cancer (e.g., UC), kidney cancer (e.g., RCC), breast cancer (e.g., TNBC), or melanoma), based on a tissue tumor mutational burden (tTMB) score, which reflects somatic mutation levels of genes in a tumor tissue sample obtained from the patient, alone or in combination with PD-L1 expression levels (e.g., PD-L1 expression levels in tumor or tumor- infiltrating immune cells in a tumor sample (tumor area) obtained from the patient).
>> Read More

MULTI-MODAL BIOPROBE FOR BLADDER CANCER IMAGING AND PHOTODYNAMIC THERAPY (Fri, 13 Apr 2018)
Provided herein is a new generation of PDT agents based on porphyrin-lanthanide complexes with specific functional groups which can specifically localize on particular tumors, and their PDT processes can be monitored via NIR emission from erbium. In particular, provided herein is a multi-modal lanthanide-porphyrin PDT agent (Er-R3) that are capable of killing the bladder tumor cells selectivity via1O2 from porphyrin moiety and affording the fluorescence imaging simultaneously upon Er-R3 binding with the integrin αvβ3 isoform in bladder cancer cells.
>> Read More

INHIBITORS OF ADENOSINE 5'-NUCLEOTIDASE (Fri, 13 Apr 2018)
Compounds that modulate the conversion of AMP to adenosine by 5'- nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5'-nueleotidase, ecto is also provided.
>> Read More

NOVEL FURAZAN-3-CARBOXYLIC ACID DERIVATIVES AND USE THEREOF IN TREATMENT OF CANCER (Fri, 13 Apr 2018)
A furazan-3-carboxylic acid derivative or pharmaceutically acceptable salt thereof for treatment of acute myeloid leukemia.
>> Read More

ANTI-CD39 ANTIBODIES (Fri, 13 Apr 2018)
The present invention relates to antibodies that inhibit CD39. The invention also relates to cells producing such compounds; methods of making such compounds, and antibodies, fragments, variants, and derivatives thereof; pharmaceutical compositions comprising the same; methods of using the compounds to diagnose, treat or prevent diseases, e.g., cancer.
>> Read More

CYANO-SUBSTITUTED HETEROCYCLES WITH ACTIVITY AS INHIBITORS OF USP30 (Fri, 13 Apr 2018)
The present invention relates to cyano-substituted-heterocycles of Formula (I) with activity as inhibitors of deubiquitilating enzymes, in particular, ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30), having utility in a variety of therapeutic areas including cancer and conditions involving mitochondrial dysfunction. (Formula (I))
>> Read More

DEUTERATED N-(5-(2,3-DIHYDROBENZO[B][1,4]DIOXINE-6-CARBOXAMIDO)-2-FLUOROPHENYL)-2-((4-ETHYLPIPERAZIN-1 -YL)METHYL)QUINOLINE-6-CARBOXAMIDE (Fri, 13 Apr 2018)
The present invention relates to N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-fluorophenyl)-2-((4-ethylpiperazin-1-yl)methyl)quinoline-6-carboxamide, or a pharmaceutically acceptable salt or solvate thereof, wherein at least one hydrogen atom has been substituted with a deuterium atom. Other aspects include pharmaceutical compositions comprising said compounds and medical uses and methods of treatment using said compounds.
>> Read More

Crystalline bromodomain inhibitors (Fri, 13 Apr 2018)
N- [4-(2,4-difluorophenoxy)-3 -(6-methyl-7-oxo-6,7-dihydro- 1 H-pyrrolo [2,3 -c]pyridin-4 yl)phenyl]ethanesulfonamide and crystalline forms thereof are suitable pharmaceutical ingredients for pharmaceutical compositions useful in the treatment of disease, for example, cancer.
>> Read More

Chimeric compounds targeting proteins, compositions, methods, and uses thereof (Wed, 11 Apr 2018)
<p id="p-0001" num="0000">The present invention provides chimeric compounds that modulate protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, TNF-alpha activity, CK1-alpha activity and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of protein-mediated diseases, disorders, and conditions, such as cytokine-mediated diseases, disorders, and conditions, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, organ transplant rejection, and cancer, are provided.</p>
>> Read More

Macrocyclic compound and uses thereof (Wed, 11 Apr 2018)
<p id="p-0001" num="0000">The present invention provides novel Compound (1) having tumor vascular remodeling effect and/or anti-CAF (Cancer Associated Fibroblasts) activity, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier, and a medical uses thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="81.53mm" wi="76.20mm" file="US09938288-20180410-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

QUINOLINE DERIVATIVES AS INHIBITORS OF HEAT SHOCK FACTOR 1 PATHWAY ACTIVITY (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">The present invention 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="18.46mm" wi="69.85mm" file="US20180093955A1-20180405-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R, R<sub>4 </sub>and Q are each as defined herein. The compounds of the present invention are inhibitors of heat shock factor 1 pathway (HSF1 pathway). In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.</p>
>> Read More

5H-PYRIDO[3,2-B]INDOLE COMPOUNDS AS ANTICANCER AGENTS (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">The present invention is directed to tricyclic compounds of formula (I), pharmaceutically acceptable compositions comprising compounds of the invention and said compositions for use in methods for the treatment of various disorders in particular cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.79mm" wi="58.42mm" file="US20180093983A1-20180405-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

GUANIDINE COMPOUNDS AND USE THEREOF (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">The present invention relates to guanidine compounds for inhibiting mitochondrial oxidative phosphorylation (OXPHOS) and use thereof. More specifically, the present invention relates to a pharmaceutical composition for preventing or treating a OXPHOS-related disease, particularly cancer by inhibiting mitochondrial oxidative phosphorylation and reprogramming cellular metabolism.</p>
>> Read More

HYDROPHOBICALLY TAGGED SMALL MOLECULES AS INDUCERS OF PROTEIN DEGRADATION (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">Provided are bifunctional small molecules of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="9.91mm" wi="48.77mm" file="US20180093990A1-20180405-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 M represents a small organic molecule which binds, covalently or non-covalently, a kinase, such as Her3 protein kinase; L<sup>1 </sup>represents a linker; and R<sup>H </sup>represents a hydrophobic group. An example of a compound of Formula (I) is a compound of Formula (II):</p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="47.58mm" wi="59.77mm" file="US20180093990A1-20180405-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005" num="0000">Also provided are pharmaceutical compositions comprising a compound of Formula (I) or (II) and methods of using such compounds for treating proliferative diseases.</p>
>> Read More

TRICYCLIC INHIBITORS OF POLY(ADP-RIBOSE)POLYMERASE (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">The invention provides for compositions comprising phosphorous containing tricyclic compounds, including phthalazin-1(2H)-one derivatives. The compounds are potent inhibitors of the enzyme poly(ADP-ribose)polymerase (PARP), particularly PARP-1 and potentially PARP-2. The also show good cellular activity in inhibiting poly(ADP-ribose) oligomer formation. The compounds may be useful as mono-therapy or in combination with other therapeutic agents in the treatment conditions where PARP is implicated, such as cancer, inflammatory diseases and ischemic conditions. Thus, also provided are methods for the treatment of a condition where PARP is implicated comprising administering to an effective amount of a compound of the invention to an individual in need thereof.</p>
>> Read More

ENZYME-DIRECTED IMMUNOSTIMULANT AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATION(S) (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">The disclosed invention relates to the novel composition of matter that allows for the controlled release of highly active compounds to be delivered to a desired site. This novel composition utilizes the immune system to allow for the controlled release of desired compounds. The present invention can utilize a plurality of highly active compounds, with one embodiment being the use of chemotherapeutics for the treatment of cancer.</p>
>> Read More

Biomarker for Predicting Colon Cancer Responsiveness to Anti-Tumor Treatment (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">The present invention provides a biomarker, namely CDX2, and surrogate CDX2 biomarkers, the expression level of which is useful in predicting response of cancer patients to therapy with an EGFR inhibitor.</p>
>> Read More

ISOQUINOLIN-3-YL CARBOXAMIDES AND PREPARATION AND USE THEREOF (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">Isoquinoline compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an isoquinoline compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.</p>
>> Read More

COMPOSITIONS TO DISRUPT PROTEIN KINASE A ANCHORING AND USES THEREOF (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">The invention provides compositions and methods for treating diseases associated with expression of a cancer associated antigen as described herein. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen and modified T-cell receptor (TCR) T cells as described herein, vectors encoding the same, and recombinant T cells comprising the CARs or TCRs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a cancer associated antigen as described herein. In one aspect, the invention includes a composition comprising a nucleic acid sequence encoding a T cell signaling molecule and a nucleic acid sequence encoding a peptide comprising an amphipathic helix domain and a cluster of basic amino acids, wherein the peptide disrupts protein kinase A and an A-kinase anchoring protein (AKAP) association. The invention also includes a peptide that disrupts the PKA and AKAP association, such as through binding the RI subunit of the PKA with high affinity, thus preventing PKA from anchoring to the cell membrane.</p>
>> Read More

MULTIMODAL SILICA-BASED NANOPARTICLES (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">The present invention provides a fluorescent silica-based nanoparticle that allows for precise detection, characterization, monitoring and treatment of a disease such as cancer. The nanoparticle has a range of diameters including between about 0.1 nm and about 100 nm, between about 0.5 nm and about 50 nm, between about 1 nm and about 25 nm, between about 1 nm and about 15 nm, or between about 1 nm and about 8 nm. The nanoparticle has a fluorescent compound positioned within the nanoparticle, and has greater brightness and fluorescent quantum yield than the free fluorescent compound. The nanoparticle also exhibits high biostability and biocompatibility. To facilitate efficient urinary excretion of the nanoparticle, it may be coated with an organic polymer, such as poly(ethylene glycol) (PEG). The small size of the nanoparticle, the silica base and the organic polymer coating minimizes the toxicity of the nanoparticle when administered in vivo. In order to target a specific cell type, the nanoparticle may further be conjugated to a ligand, which is capable of binding to a cellular component associated with the specific cell type, such as a tumor marker. In one embodiment, a therapeutic agent may be attached to the nanoparticle. To permit the nanoparticle to be detectable by not only optical fluorescence imaging, but also other imaging techniques, such as positron emission tomography (PET), single photon emission computed tomography (SPECT), computerized tomography (CT), bioluminescence imaging, and magnetic resonance imaging (MRI), radionuclides/radiometals or paramagnetic ions may be conjugated to the nanoparticle.</p>
>> Read More

SPIROCYCLIC COMPOUNDS AS TRYPTOPHAN HYDROXYLASE INHIBITORS (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">The present invention is directed to spirocyclic compounds which are inhibitors of tryptophan hydroxylase (TPH), particularly isoform 1 (TPH1), that are useful in the treatment of diseases or disorders associated with peripheral serotonin including, for example, gastrointestinal, cardiovascular, pulmonary, inflammatory, metabolic, and low bone mass diseases, as well as serotonin syndrome, and cancer.</p>
>> Read More

SALTS AND POLYMORPHS OF 8-FLUORO-2-{4-[(METHYLAMINO)METHYL]PHENYL}-1,3,4,5-TETRAHYDRO-6H-AZEPINO[5,4,3-CD]INDOL-6-ONE (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">The present invention relates to novel polymorphic forms of 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one, and to processes for their preparation. Such polymorphic forms may be a component of a pharmaceutical composition and may be used to treat a mammalian disease condition mediated by poly(ADP-ribose) polymerase activity including the disease condition such as cancer.</p>
>> Read More

COMPOUNDS FOR TREATMENT OF CANCER (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">The present invention relates to a compound of formula XXII and a compound of formula 17ya, which are defined as anywhere in the specification, to a composition comprising the same, and to a method of using thereof in the treatment of various forms of cancer.</p>
>> Read More

HETEROARYL AMIDES AS INHIBITORS OF PROTEIN AGGREGATION (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">The present invention relates to certain heteroaryl amide compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer and melanoma.</p>
>> Read More

1-PHENYLPROPANONE COMPOUNDS AND USE THEREOF (Fri, 06 Apr 2018)
The present invention relates to a 1-phenylpropanone compound of formula (I), wherein X is CH2 or an atom selected from the group consisting of O, S and Se, n is an integer from 4 to 6, A is a substituent selected from the group consisting of 4-morpholyl, 1-piperidinyl, 4-methyl-1-piperazinyl, A being optionally substituted with a (C1-C3)alkyl or (C1-C3)acyl substituent, with the proviso that when X is CH2, n is equal to 5, for use as an antitumoral agent in the treatment of breast cancer, chronic lymphatic leukemia or neuroblastoma. The invention also concerns new 1-phenylpropanone compounds, and compounds as antitumoral agents.
>> Read More

TREATMENT CANCERS USING COMBINATION COMPRISING PARP INHIBITORS (Fri, 06 Apr 2018)
Disclosed herein is a method for the prevention, delay of progression or treatment of cancer in a subject, comprising administering to the subject in need thereof a PARP inhibitor, particularly, (R) -2-fluoro-10a-methyl-7, 8, 9, 10, 10a, 11-hexahydro-5, 6, 7a, 11-tetraazacyclohepta [def] cyclopenta [a] fluoren-4 (5H) -one, a sesqui-hydrate thereof, or a pharmaceutically acceptable salt thereof, in combination with an immune checkpoint inhibitor or a chemotherapeutic agent. Also, disclosed a pharmaceutical combination comprising a PARP inhibitor, particularly, (R) -2-fluoro-10a-methyl-7, 8, 9, 10, 10a, 11-hexahydro-5, 6, 7a, 11-tetraazacyclohepta [def] cyclopenta [a] fluoren-4 (5H) -one, a sesqui-hydrate thereof, or a pharmaceutically acceptable salt thereof, in combination with an immune checkpoint inhibitor, or a chemotherapeutic agent and the use thereof.
>> Read More

CHELATING MOLECULES (Fri, 06 Apr 2018)
Provided herein are a variety of metal chelators as well as methods of use thereof.
>> Read More

METHOD FOR TREATING CANCER USING A COMBINATION OF DNA-DAMAGING AGENTS AND DNA-PK INHIBITORS (Fri, 06 Apr 2018)
Described herein are methods of treating a proliferative disease in a subject by administering a DNA-damaging agent and between about 8 and about 48 hours later administering to the subject a DNA-PK inhibitor. Exemplary DNA-PK inhibitors are represented by Formula (B-I): and by pharmaceutically acceptable salts thereof, wherein R1, Q, Ring A, and Ring B are as defined herein.
>> Read More

THERAPEUTIC MOTS-C RELATED PEPTIDES (Fri, 06 Apr 2018)
Provided herein are peptides and peptide analogs and methods of treating a metabolic disease, e.g., obesity, diabetes, methods of treating cancer, methods of treating a liver disease, and methods of modulating fatty acid metabolism.
>> Read More

INHIBITORS OF KRAS G12C MUTANT PROTEINS (Fri, 06 Apr 2018)
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I), or a pharmaceutically acceptable salt, tautomer, stereoisomer or prodrug thereof, wherein B, W, X, Y, R1, R2a, R2b, R3a, R3b, R4a, R4b, G1, G2, m1, m2, L1, L2 and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.
>> Read More

DUAL CLK/CDK1 INHIBITORS FOR CANCER TREATMENT (Fri, 06 Apr 2018)
This disclosure generally relates to dual CLK2/CDK1 inhibitors or more potent and specific CLK inhibitors to target CLK2 and CDKl kinases in the treatment of germ-line mutations of the spliceosome leading to the development of cancers and other human disease. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
>> Read More

TARGETED PROTEIN DEGRADATION USING A MUTANT E3 UBIQUITIN LIGASE (Fri, 06 Apr 2018)
The present application provides bifunctional compounds of Formula I or II: or an enantiomer, diastereomer, or stereoisomer, or a pharmaceutically acceptable salt thereof, 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 of Formula (I) or (II) that link a mutant cereblon-binding moiety to a ligand that is capable of binding to a 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. The present application also relates to polynucleotides or polypeptides of a mutant cereblon and methods of use thereof.
>> Read More

RETINOID DERIVATIVES WITH ANTITUMOR ACTIVITY (Fri, 06 Apr 2018)
The present invention relates to compounds of formula (I) and to pharmaceutical compositions containing them, wherein meanings of the substituents are indicated in the description. Such compounds for use in the treatment of cancer and other diseases related to altered angiogenesis, such as arthritic pathology, diabetic retinopathy, psoriasis and chronic inflammatory disease, are also within the scope of the present invention.
>> Read More

TREATMENT OF PROSTATE CANCER (Fri, 06 Apr 2018)
Methods for treating prostate cancer, including advanced prostate cancer, in a subject in need thereof, include administering once-daily to the subject, at least 80 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N'-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof. Another method includes: administering once-daily to the subject in need thereof, an oral load dose formulation having from 240 mg to 480 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethylamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N'-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof; and thereafter administering once-daily to the subject, an oral maintenance dose formulation having 80 mg to 160 mg of N-(4-(1-(2,6-difluorobenzyl)-5-((dimethyiamino)methyl)-3-(6-methoxy-3-pyridazinyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl)phenyl)-N'-methoxyurea, or a corresponding amount of a pharmaceutically acceptable salt thereof.
>> Read More

CYANO-SUBTITUTED HETEROCYCLES WITH ACTIVITY AS INHIBITORS OF USP30 (Fri, 06 Apr 2018)
The present invention relates to a class of cyano-substituted-heterocycles of Formula (I) with activity as inhibitors of deubiquitilating enzymes, in particular, ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30), having utility in a variety of therapeutic areas including cancer and conditions involving mitochondrial dysfunction. (I)
>> Read More

CYANOPYRROLIDINE DERIVATIVES WITH ACTIVITY AS INHIBITORS OF USP30 (Fri, 06 Apr 2018)
The present invention relates to substituted-cyanopyrrolidines of Formula (I) with activity as inhibitors of deubiquitilating enzymes, in particular, ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30), having utility in a variety of therapeutic areas including cancer and conditions involving mitochondrial dysfunction. (I)
>> Read More

PYRIDINE COMPOUND (Fri, 06 Apr 2018)
The present invention relates to a compound having RET kinase inhibiting action or a pharmaceutically acceptable salt thereof, useful in the treatment of diseases such as cancer. In particular a compound represented by the following general formula (I) as defined herein: (I) or a pharmaceutically acceptable salt thereof.
>> Read More

CYANOPYRROLIDINE DERIVATIVES WITH ACTIVITY AS INHIBITORS OF USP30 (Fri, 06 Apr 2018)
The present invention relates to a class of substituted-cyanopyrrolidines of Formula (I) with activity as inhibitors of deubiquitilating enzymes, in particular, ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30), having utility in a variety of therapeutic areas including cancer and conditions involving mitochondrial dysfunction. (Formula (I))
>> Read More

SUBSTITUTED N-(1H-INDAZOL-4-YL)IMIDAZO[1,2-a]PYRIDINE-3-CARBOXAMIDE COMPOUNDS AS TYPE III RECEPTOR TYROSINE KINASE INHIBITORS (Fri, 06 Apr 2018)
[007801 Compounds of Formula I: and pharmaceutically acceptable salts thereof in which R', R2, R, R4, R5 and R6 have the meanings given in the specification, are inhibitors of cFMS and are useful in the treatment of fibrosis, bone-related diseases, cancer, autoimmune disorders, inflammatory diseases, cardiovascular diseases, pain and burns in a mammal.
>> Read More

Dioxolane analogues of uridine for the treatment of cancer (Fri, 06 Apr 2018)
The invention provides compounds of formula (1), wherein: R is OR", or NR5RT
>> Read More

RETINOID DERIVATIVES WITH ANTITUMOR ACTIVITY (Thu, 05 Apr 2018)
The present invention relates to new compounds of formula (I) and to pharmaceutical compositions containing them: The use of such compounds for the treatment of cancer and other diseases related to altered angiogenesis, such as arthritic pathology, diabetic retinopathy, psoriasis and chronic inflammatory disease, is also within the scope of the present invention.
>> Read More

NEW COMPOUNDS FOR TREATING CANCER AND OTHER DISEASES (Thu, 05 Apr 2018)
This invention provides a method of synthesizing new active compounds for pharmaceutical uses including cancer treatment, wherein the cancers comprise breast, leukocytic, liver, ovarian, bladder, prostatic, skin, bone, brain, leukemia, lung, colon, CNS, melanoma, renal, cervical, esophageal, testicular, spleenic, kidney, lymphatic, pancreatic, stomach and thyroid cancers. This invention is an anti adhesion therapy which uses the compound as a mediator or inhibitor of adhesion proteins and angiopoietins. It inhibits excess adhesion and inhibits cell attachment. It modulates angiogenesis. The compounds also use as mediator of cell adhesion receptor, cell circulating, cell moving and inflammatory diseases.
>> Read More

SPECIFIC BINDING PROTEINS AND USES THEREOF (Thu, 05 Apr 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

ANTI-GLOBO H ANTIBODIES (Fri, 30 Mar 2018)
Provided herein are engineered antibodies that bind Globo H with high affinity and have increased stability against undesirable chemical modifications and large aggregate formation that can occur under high expression manufacturing conditions. Also provided are methods of manufacturing, pharmaceutical formulations, and uses of the engineered antibodies for the treatment of cancer.
>> Read More

PREPARATION AND USES OF PYRIMIDINONE DERIVATIVES (Fri, 30 Mar 2018)
The present invention relates to compounds of formula (I), and salts and solvates thereof, that function as inhibitors of cell division cycle 7 (Cdc7) kinase enzyme activity: (Formula (I)) wherein X, R1, R2, and n 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 Cdc7 kinase activity is implicated.
>> Read More

EXTRACTS OF SAUDI ARABIAN HERBAL PLANTS, ANTI-CANCER METHOD USING SUCH EXTRACTS, AND CYTOLOGICAL PROFILING USING AUTOMATED HIGH-CONTENT IMAGING TECHNIQUE (Fri, 30 Mar 2018)
Cell-based phenotypic profiling and image based high-content screening are used to gain insight into the mode of action and potential cellular targets of plants historically used to determine anti-cancer activity of Saudi Arabian plants Juniperus phoenicea (Arar), Anastatica hierochuntica (Kaff Maryam), and Citrullus colocynthis (Hanzal). The cytological profiles of fractions taken from the plants were compared with a set of reference compounds with known modes of action. Cluster analyses of the cytological profiles were performed, which revealed detailed information on the modes of action of the tested compounds as potential topoisomerase inhibitors. Cytological profiles showed that some of these compounds inhibited cell proliferation causing cell cycle disruption.
>> Read More

COMPOUND FOR INHIBITING THE GROWTH AND PROLIFERATION OF HUMAN LIVER CANCER CELLS AND METHOD FOR SYNTHESIZING IT (Fri, 30 Mar 2018)
The compound 2-((4-nitrophenyl)amino)-6,7,8,9-tetrahydro-3H-cyclohepta[4,5]thieno[2, 3-d]pyrimidin-4(5H)-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 an inhibitory 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 Doxorubicin at all tested concentraions. The method includes the steps of: preparing a first compound of cycloheptanone, ethyl cyanoacetate, sulfur, ethanol and diethyl amine; preparing a second compound by heating of the first compound with excess of hydrazine hydrate in absolute ethanol as solvent; and preparing the effective compound of the invention by reaction of the second chemical compound with 4-nitrophenylisothiocyanate in dry dimethylformamide as solvent.
>> Read More

METHODS AND COMPOSITIONS FOR INHIBITING SKIN INFLAMMATION AND DETERMINING CANCER SUSCEPTIBILITY (Fri, 30 Mar 2018)
Disclosed herein are methods of treating or preventing an autoimmune skin disorder and/or inflammatory skin disorder, skin tumor and obesity in a subject in need thereof by administering an inhibitor capable of inhibiting the activation of inflammasome NLRP1, NLRP1 mutants, an agent that prevents the secretion of stress responsive secreted factors, known pro-inflammatory cytokines, keratinocytes differentiation markers, inflammasome-dependent cytokines, and growth factors in the skin and an agent that reduces the effect of inflammasome-dependent cytokines. The invention encompasses the use of an activator of NLRP1, such as talabostat, specifically for treating skin tumors. Also enclosed herein are methods of determining the likelihood of a subject in developing an autoimmune skin disorder and/or inflammatory skin disorder comprising detecting NLRP1 mutation in a sample obtained from the subject. An inflammasome sensor NLRP1 mutant and compositions for treatment are also disclosed.
>> Read More

BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS (Fri, 30 Mar 2018)
The present application provides the compounds of formula I or IA or pharmaceutically acceptable salts, isomers, tautomer, or a mixture thereof, wherein s, t, m, n, R1, R2, R3, R4, R5, R6 and R7are as described herein. The compounds of formula I or IA selectively inhibit the activities of PI3K isoforms and are therefore useful in therapeutic treatments, in particular in the treatment of cancer and inflammatory conditions.
>> Read More

COMPOSITIONS AND METHODS FOR IDENTIFICATION, ASSESSMENT, PREVENTION, AND TREATMENT OF AML USING USP10 BIOMARKERS AND MODULATORS (Fri, 30 Mar 2018)
The present invention is based, in part, on the identification of novel USP10 biomarkers and modulators, and methods of use thereof, for identifying, assessing, preventing, and treating AML.
>> Read More

TAGGED POLY(ESTER AMIDE URETHANE)S, NANOPARTICLES FORMED FROM SAME, AND USES THEREOF (Fri, 30 Mar 2018)
Provided are polymers (e.g., polymeric materials), nanoparticles comprising one or more of the polymers, and compositions. A polymer may be in the form of a nanoparticle. A polymer can be linear or branched. A polymer includes one or more poly(ester urea) segment, optionally, one or more poly(urethane) segment, optionally, one or more diol segment, optionally, one or more poly(ethylene glycol) segment, and, optionally, one or more terminal/end group. A polymer (e.g., a polymeric material) may include a branching moiety. For example, a composition includes one or more polymer. In an example, polymers and nanoparticles can be used to deliver a drug (e.g., gambogic acid) to an individual (e.g, who has been diagnosed with or is suspected of having cancer and/or a viral infection).
>> Read More

BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS (Fri, 30 Mar 2018)
The present application provides the compounds of formula I or pharmaceutically acceptable salts, isomers, tautomer, or a mixture thereof, wherein t, R1, R2, R3, R4, and R6 are as described herein. The compounds of formula I selectively inhibit the activities of PI3K isoforms and are useful in therapeutic treatments, in particular in the treatment of inflammatory diseases and cancer.
>> Read More

SHP2 PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF (Fri, 30 Mar 2018)
The present invention relates to novel compounds and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the invention. The present invention further relates to, but is not limited to, methods for suppressing tumor cell growth, ameliorating the pathogenesis of systemic lupus erythematosus, and the treatment of various other disorders, including Noonan syndrome, diabetes, neutropenia, neuroblastoma, melanoma, juvenile leukemia, juvenile myelomonocytic leukemia, chronic myelomonocytic leukemia, acute myeloid leukemia, and other cancers associated with SHP2 deregulation with the compounds and compositions of the invention, alone or in combination with other treatments. Other cancers associated with SHP2 deregulation include HER2-positive breast cancer, triple-negative breast cancer, ductal carcinoma of the breast, invasive ductal carcinoma of the breast, non-small cell lung cancer, esophageal cancer, gastric cancer, squamous-cell carcinoma of the head and neck (SCCHN), and colon cancer.
>> Read More

ANTI-CANCER AGENTS AND PREPARATION THEREOF (Fri, 30 Mar 2018)
Embodiments provide, among other compounds, a family of compounds that can be used as therapeutic anti-cancer agents, methods for using such compounds to treat cancer, and methods of making such compounds.
>> Read More

CHROMOBOX PROTEIN INHIBITORS AND USES THEREOF (Fri, 30 Mar 2018)
Provided herein are compounds useful as inhibitors of CBX. Also described are pharmaceutical compositions and medical uses of these compounds.
>> Read More

BENZOIMIDAZOLE DERIVATIVES AS ANTICANCER AGENTS (Fri, 30 Mar 2018)
The invention relates to benzoimidazole derivatives, acting as anticancer drugs, as well as pharmaceutical composition containing said compounds. These compounds are able to firstly inhibit the protein/protein interactions of the MAP Kinase Erk, leading to inhibition of proliferation and secondly to induce apoptosis in human cancer cell lines.
>> Read More

TRITERPENE SAPONINS, METHODS OF SYNTHESIS, AND USES THEREOF (Fri, 30 Mar 2018)
[003611 The present invention relates to triterpene glycoside saponin-derived adjuvants, syntheses thereof, intermediates thereto, and uses thereof. QS-7 is a potent immune-adjuvant that is significantly less toxic than QS-21, a related saponin that is currently the favoured adjuvant in anticancer and antiviral vaccines. Tedious isolation and purification protocols have hindered the clinical development of QS-7. A novel semi-synthetic method is provided wherein a hydrolyzed prosapogenin mixture is used to synthesize QS-7, QS-21, and related analogs, greatly facilitating access to QS-7 and QS-21 analogs for preclinical and clinical evaluation.
>> Read More

DEVICES, SYSTEMS, AND METHODS FOR EXCAVATING CANCER CELLS (Thu, 29 Mar 2018)
Methods, devices, and systems are provided for guiding tumor movement, particularly in vivo for treatment of patients. The method may include implanting into a tissue site where tumor cells are present a device having one or more surface structures or substrates, such as aligned nanofibers, which provide physical guidance cues for directing the migration of the tumor cells from the first tissue location to a selected second location, for tumor cell extraction or death. The devices and systems may include a cytotoxic agent for contacting tumor cells migrated via the substrate. All or a portion of the at least one substrate may include one or more biochemical cues, such as a coating of laminin or another protein, which may be provided in a concentration gradient to facilitate uni - directional tumor cell migration.
>> Read More

PYRAZOLE DERIVATIVES AS MODULATORS OF CALCIUM RELEASE-ACTIVATED CALCIUM CHANNEL (Thu, 29 Mar 2018)
Disclosed are novel calcium release-activated calcium (CRAC) channel inhibitors, methods for preparing them, pharmaceutical compositions containing them, and methods of treatment using them. The present disclosure also relates to methods for treating non-small cell lung cancer (NSCLC) with CRAC inhibitors, and to methods for identifying therapeutics for treating and of diagnosing cancer.
>> Read More

IMIDAZOL-PIPERIDINYL DERIVATIVES AS MODULATORS OF KINASE ACTIVITY (Thu, 29 Mar 2018)
The invention provides novel imidazol-piperidinyl derivatives of formula (I) in which R 1 , R 2 , X 1 , X 2 , X 3 , X 4 and n have the meanings indicated in above, and their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.
>> Read More

PYRIDO-AZAHETERECYDIC COMPOUND AND PREPARATION METHOD AND USE THEREOF (Thu, 29 Mar 2018)
The present inveniton discloses a pyrido-azacyclic compound represented by formula I, an isomer thereof, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, a preparation process thereof and a composition comprising the compound, and a use thereof as a multi-target protein kinase inhibitor in the preparation of a medicament for the treatment of diseases that are associated with protein kinase, especially c-Met, such as cancer and the like. The compound represented by formula I has potent inhibitory activity on tumor cells with overexpression of c-Met kinase, can effectively target c-Met-mediated signaling pathway, and can be used in the treatment of diseases such as cancer and the like that is caused by the overexpression of c-Met kinase.
>> Read More

GLAUCOCALYXIN A DERIVATIVE AND PREPARATION METHOD AND APPLICATION THEREOF (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">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</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.86mm" wi="69.85mm" file="US20180079711A1-20180322-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

(HETERO)ARYL CYCLOPROPYLAMINE COMPOUNDS AS LSD1 INHIBITORS (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula (I) as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="16.51mm" wi="69.85mm" file="US20180079709A1-20180322-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

MONOCYCLIC COMPOUND (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">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.</p>
>> Read More

BENZODIAZEPINE DIMERS, CONJUGATES THEREOF, AND METHODS OF MAKING AND USING (Fri, 23 Mar 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="39.03mm" wi="69.85mm" file="US20180079781A1-20180322-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1 </sup>is</p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="85.09mm" wi="69.85mm" file="US20180079781A1-20180322-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005" num="0000">wherein the 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

ACTIVE METABOLITES OF APILIMOD AND USES THEREOF (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">The present invention relates to compositions comprising one or more active metabolites of apilimod and methods for their use in treating cancer.</p>
>> Read More

METHODS AND MATERIALS FOR TREATING CANCER (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">This document provides methods and materials for treating cancer. For example, this document provides methods for using compositions containing a potato polysaccharide preparation to reduce the number of cancer cells in a mammal. In some cases, a composition containing a potato polysaccharide preparation provided herein can be used to reduce the number of cancer cells in a mammal, wherein the cancer cells express a KRAS polypeptide.</p>
>> Read More

NOVEL SUBSTITUTED 6,7-DIHYDRO-5H-BENZO[7]ANNULENE COMPOUNDS, PROCESSES FOR THEIR PREPARATION AND THERAPEUTIC USES THEREOF (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">Compounds of formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="59.86mm" wi="69.85mm" file="US20180079720A1-20180322-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R1 and R2 represent hydrogen or deuterium atoms; R3 represents a hydrogen atom or a —COOH, a —OH or a —OPO(OH)<sub>2 </sub>group; R4 represents a hydrogen atom or a fluorine atom; R5 represents a hydrogen atom or a —OH group; wherein at least one of R3 or R5 is different from a hydrogen atom; when R3 represents a —COOH, —OH or —OPO(OH)<sub>2 </sub>group, then R5 represents a hydrogen atom; when R5 represents a —OH group, then R3 and R4 represent hydrogen atoms; and R6 is selected from an optionally substituted phenyl, heteroaryl, cycloalkyl and heterocycloalkyl group; <br/> and the preparation and the therapeutic uses of the compounds of formula (I) as inhibitors and degraders of estrogen receptors, useful especially in the treatment of cancer. </p>
>> Read More

INHIBITORS OF INDOLEAMINE-2,3-DIOXYGENASE FOR THE TREATMENT OF CANCER (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">There are disclosed compounds of formula (I) that modulate or inhibit the enzymatic activity of indoleamine-2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the invention.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="58.00mm" file="US20180079712A1-20180322-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

PROCESS FOR THE SYNTHESIS OF E1 ACTIVATING ENZYME INHIBITORS (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">The present invention provides processes and synthetic intermediates for the synthesis of 4-substituted ((4S, 2S, 4R)-2-hydroxy-4-{7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentyl)methyl sulfamates, which are E1 activating enzyme inhibitors, and are useful for the treatment of disorders of cell proliferation, particularly cancer, and other disorders associated with E1 activity.</p>
>> Read More

Carbon-Detected NMR For Mapping Binding Sites In Intrinsically Disordered Regions Of A Protein (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">Carbon-detected NMR is well-suited for mapping binding sites in intrinsically disordered regions of a polypeptides, and for mapping of binding motifs in intrinsically disordered regions with single-residue resolution. Provided are methods of carbon-detected NMR for determining the amino acids that mediate the interaction between an intrinsically disordered polypeptide or protein, or an intrinsically disordered region of a polypeptide, and a biomolecule such as another polypeptide or a nucleic acid.</p>
>> Read More

BETA-SUBSTITUTED BETA-AMINO ACIDS AND ANALOGS AS CHEMOTHERAPEUTIC AGENTS (Fri, 23 Mar 2018)
<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

METHODS FOR TREATING CANCER WITH TRKA RECEPTOR TYROSINE KINASE ANTAGONISTS (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">The present disclosure relates to novel synthetic substituted heterocyclic compounds and pharmaceutical compositions containing the same, said compounds being capable of inhibiting or antagonizing TrkA receptor tyrosine kinases. In some aspects, the disclosure provides a compound having a structural formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="40.64mm" wi="64.77mm" file="US20180078545A1-20180322-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The disclosure further concerns the use of such compounds in the treatment and/or prevention of certain types of cancers, pain, inflammation, restenosis, atherosclerosis, psoriasis, thrombosis, Alzheimer's, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination.</p>
>> Read More

NOVEL THERAPIES FOR CANCER (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">The invention relates to 6-{4-[1-(Propan-2-yl)piperidin-4-yl]-1,4-diazepan-1-yl}-N-(pyridin-4-yl)pyridine-2-carboxamide, or a pharmaceutically acceptable salt thereof, for use in treatment of CNS cancers. The invention also relates to combination treatments with irradiation and/or a chemotherapeutic agent for use in the treatment of cancer</p>
>> Read More

CRYPTOPHYCIN-BASED ANTIBODY-DRUG CONJUGATES WITH NOVEL SELF-IMMOLATIVE LINKERS (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">The present invention relates to antibody- or peptide-drug conjugate compounds where one or more cryptophycin derivatives (macrocyclic depsipeptide) are covalently attached by a self-immolative linker which binds to one or more tumor-associated antigens or cell-surface receptors. The linker contains a cleavage site for proteases and a dipeptide unit able to form a diketopiperazine. These compounds may be useful in methods of diagnosis or treatment of cancer, and other diseases and disorders, such as immune or infective diseases.</p>
>> Read More

NOVEL PEPTIDE COMPOUND, PRODUCTION METHOD THEREFOR, AND USE THEREOF (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">Provided are a novel peptide compound, a method of producing the same, and use of the peptide compound. Since the peptide compound has anticancer activity, the peptide compound may be used for the prevention or treatment of cancer.</p>
>> Read More

TRAF 6 INHIBITORS (Fri, 23 Mar 2018)
The invention relates to compounds which are suitable for the treatment of cancer, an immune disease, Parkinson's disease, Cardiac Hypertrophy or Type-2 diabetes and to pharmaceutical compositions containing such compounds. The invention further relates to a kit of parts comprising such compounds.
>> Read More

INHIBITORS OF HEAT SHOCK FACTORS AND USES THEREOF (Fri, 23 Mar 2018)
The present disclosure relates to a class of mammalian heat shock factor (HSF) inhibitors, to pharmaceutical compositions comprising these inhibitors as well as to methods for using the inhibitors. The inhibitors inhibit stress-induced expression from heat shock gene promoters. Furthermore, the inhibitors are cytotoxic to a variety of human cancer cells types.
>> Read More

FUSED BICYCLIC INHIBITORS OF MENIN-MLL INTERACTION (Fri, 23 Mar 2018)
The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a mammal, and in particular to fused bicyclic compounds, pharmaceutical composition comprising such compounds, and their use as menin/MLL protein/protein interaction inhibitors, useful for treating diseases such as cancer, myelodysplastic syndrome (MDS) and diabetes.
>> Read More

Site Search