Cancer

NEW MOLECULES FROM SEAWEEDS WITH ANTI-CANCER ACTIVITY (Sat, 27 May 2017)
The present invention provides purified compounds extracted from seaweeds having the formula (I): wherein R1 and R2 is each independently H or a fatty acid and their use for inhibiting the growth of cancer cells.
>> Read More

QUINOLONE CHALCONE COMPOUNDS AND USES THEREOF (Sat, 27 May 2017)
The present disclosure relates to novel compounds, compositions comprising these compounds, and their use, for example for the treatment of cancer. In particular, the present disclosure includes compounds of Formula (I), and compositions and uses thereof.
>> Read More

NOVEL COMPOUNDS AS INHIBITORS OF DNA METHYLTRANSFERASES (Sat, 27 May 2017)
It relates to the compounds of formula (I), or their pharmaceutically or veterinary acceptable salts, or their stereoisomers or mixtures thereof, wherein A, R1, R2, and R3 are as defined herein, which are inhibitors of one or more DNMTs selected from the group consisting of DNMT1, DNMT3A and DNMT3B. It also relates to pharmaceutical or veterinary compositions containing them, and to their use in medicine, in particular in the treatment and/or prevention of cancer, fibrosis and/or immunomodulation.
>> Read More

(R)- AND (S)-1-(3-(3-N,N-DIMETHYLAMINOCARBONYL)PHENOXYL-4-NITROPHENYL)-1-ETHYL-N,N'-BIS (ETHYLENE)PHOSPHORAMIDATE, COMPOSITIONS AND METHODS FOR THEIR USE AND PREPARATION (Sat, 27 May 2017)
Provided herein are optically active compounds of the formulae (ii); and (III) and pharmaceutical compositions thereof. Also provided herein are processes of making these compounds and resolving the racemic mixture or the enrichment of same with in one of its enantiomers to provide (R)- and (S)-1-(3-(3-N,N-dimethylaminocarbonyl)phenoxyl-4-nitrophenyl)-1-ethyl-N,N'-bis(ethylene)phosphoramidate, and methods of treating cancer comprising administering such compounds.
>> Read More

2-SUBSTITUTED QUINAZOLINE COMPOUNDS COMPRISING A SUBSTITUTED HETEROCYCLIC GROUP AND METHODS OF USE THEREOF (Sat, 27 May 2017)
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): (I) or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein R1, R2a, R2b, R2c, R3a, R3b, R4a, R4b, R5a, R5b, R6, A, G1, G2, L1, L2, m1, m2, n, X and E are as defined herein, and wherein at least one of R3a, R3b, R4a or R4b is not H. 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

PD-L1-BINDING AGENTS AND USES THEREOF (Sat, 27 May 2017)
Agents that specifically bind PD-L1 are disclosed. The PD-L1-binding agents may include polypeptides, antibodies, bispecific agents, homodimeric molecules, and/or heterodimeric molecules. Also disclosed are methods of using the agents for enhancing the immune response and/or treatment of diseases such as cancer.
>> Read More

A SOLID STATE FORM OF PLADIENOLIDE PYRIDINE COMPOUNDS AND METHODS OF USE (Sat, 27 May 2017)
The present disclosure provides a novel solid state form of pladienolide pyridine compounds, compositions comprising at least one such solid state form, and methods of preparation and use and the same. The novel solid state form of pladienolide pyridine compounds may be useful in the treatment of cancer, such as, for example, cancers in which agents that target the spliceosome and mutations therein are known to be useful.
>> Read More

ANTIBODIES AGAINST GLUCOCORTICOID-INDUCED TUMOR NECROSIS FACTOR RECEPTOR (GITR) AND USES THEREOF (Sat, 27 May 2017)
Provided herein are antibodies, or antigen binding portions thereof, that bind to glucocorticoid-inducible TNF receptor (GITR). Also provided are uses of these proteins in therapeutic applications, such as in the treatment of cancer. Further provided are cells that produce the antibodies, polynucleotides encoding the heavy and/or light chain variable region of the antibodies, and vectors comprising the polynucleotides encoding the heavy and/or light chain variable region of the antibodies.
>> Read More

DUAL SRC/P38 KINASE INHIBITOR COMPOUNDS AND THEIR USE AS THERAPEUTIC AGENTS (Sat, 27 May 2017)
Dual Src/p38 kinase inhibitor compounds and compositions comprising the same are disclosed. Methods of using the compounds in the treatment of hyperproliferative disease such as cancer are also disclosed.
>> Read More

BIOCOMPATIBLE PARTICLES AND METHODS OF MAKING AND USE THEREOF (Sat, 27 May 2017)
Biocompatible particles comprising a metallic core and a plurality of drug-loading ligands coordinated to the metallic core are described. The metallic core can, for example, have a melting point of 100°C or less. The biocompatible particles can, in some examples, further comprise a therapeutically effective amount of a drug coordinated to the plurality of drug-loading ligands. In some examples, the biocompatible particles can further comprise a plurality of targeting ligands coordinated to the metallic core. Also disclosed herein are methods of making the biocompatible particles described herein, for example using sonication. Also disclosed herein are methods of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of the biocompatible particles or compositions disclosed herein.
>> Read More

ANTIBODIES AGAINST GLUCOCORTICOID-INDUCED TUMOR NECROSIS FACTOR RECEPTOR (GITR) AND USES THEREOF (Fri, 26 May 2017)
<p id="p-0001" num="0000">Provided herein are antibodies, or antigen binding portions thereof, that bind to glucocorticoid-inducible TNF receptor (GITR). Also provided are uses of these proteins in therapeutic applications, such as in the treatment of cancer. Further provided are cells that produce antibodies, polynucleotides encoding the heavy and/or light chain variable region of the antibodies, and vectors comprising the polynucleotides encoding the heavy and/or light chain variable region of the antibodies.</p>
>> Read More

DIAGNOSTIC TEST FOR EARLY STAGE CANCER (Fri, 26 May 2017)
<p id="p-0001" num="0000">Disclosed are methods of identifying tumor-derived exosomes as an early cancer diagnostic, as well as for staging, assessing progression and assessing therapy of cancer.</p>
>> Read More

CRYSTALLINE FORMS AND PROCESSES FOR THE PREPARATION OF CANNABINOID RECEPTOR MODULATORS (Fri, 26 May 2017)
<p id="p-0001" num="0000">The present invention relates to crystalline forms of (1aS,5aS)-2-(4-oxy-pyrazin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)-1-hydroxymethyl-2,2-dimethyl-propyl)-amide (Compound 1) and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB<sub>2 </sub>receptor and are therefore useful in the treatment of CB<sub>2 </sub>receptor-mediated disorders, for example, osteoarthritis; pain; hyperalgesia; allodynia; inflammatory hyperalgesia; neuropathic hyperalgesia; acute nociception; osteoporosis; multiple sclerosis-associated spasticity; autoimmune disorders; allergic reactions; CNS inflammation for example; atherosclerosis; undesired immune cell activity, and inflammation associated with a disorder selected from: osteoarthritis, anaphylaxis, Behcet's disease, graft rejection, vasculitis, gout, spondylitis, viral disease, bacterial disease, lupus, inflammatory bowel disease, autoimmune hepatitis, and type 1 diabetes mellitus; age-related macular degeneration; cough; leukemia; lymphoma; CNS tumors; prostate cancer; Alzheimer's disease; stroke-induced damage; dementia; amyotrophic lateral sclerosis; and Parkinson's disease.</p>
>> Read More

PYRIMIDINE-2,4-DIAMINE DERIVATIVE AND ANTICANCER PHARMACEUTICAL COMPOSITION COMPRISING SAME AS EFFECTIVE INGREDIENT (Fri, 26 May 2017)
<p id="p-0001" num="0000">The present invention relates to a pyrimidine-2,4-diamine derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition for prevention or treatment of cancer comprising the same as an effective ingredient. A compound according to the present invention has the good effect of inhibiting anaplastic lymphoma kinase (ALK) activity, whereby a therapeutic effect on cancer cells having an anaplastic lymphoma kinase (ALK) fusion protein such as EML4-ALK, NPM-ALK, etc. can be enhanced and it is expected that a recurrence of cancer will be effectively inhibited. As such, the compound can be effectively used in a pharmaceutical composition for prevention or treatment of cancer.</p>
>> Read More

DIHYDROPTERIDINONE DERIVATIVES AND USES THEREOF (Fri, 26 May 2017)
<p id="p-0001" num="0000">The present disclosure provides compounds of Formula (I), and pharmaceutically compositions thereof. Compounds of Formula (I) have been found to bind bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits of the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, neurological diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.</p>
>> Read More

KINASE INHIBITOR (Fri, 26 May 2017)
<p id="p-0001" num="0000">[Problem]</p> <p id="p-0002" num="0000">To provide a novel PIM-3 inhibitor and a novel cancer therapeutic drug, in particular, a therapeutic drug for pancreatic cancer.</p> <p id="p-0003" num="0000">[Solution]</p> <p id="p-0004" num="0000">A PIM-3 kinase inhibitor comprising a compound represented by general formula (I) or a pharmacologically acceptable salt, hydrate or solvate thereof.</p> <p id="p-0005" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.34mm" wi="69.85mm" file="US20170145005A1-20170525-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

METHODS AND COMPOSITIONS OF MOLECULAR PROFILING FOR DISEASE DIAGNOSTICS (Fri, 26 May 2017)
<p id="p-0001" num="0000">The present invention relates to compositions, kits, and methods for molecular profiling and cancer diagnostics, including but not limited to gene expression product markers, alternative exon usage markers, and DNA polymorphisms associated with cancer. In particular, the present invention provides molecular profiles associated with thyroid cancer, methods of determining molecular profiles, and methods of analyzing results to provide a diagnosis.</p>
>> Read More

Algorithms for Disease Diagnostics (Fri, 26 May 2017)
<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

COMPOUNDS, COMPOSITIONS AND METHODS OF AGELASTATIN ALKALOIDS (Fri, 26 May 2017)
<p id="p-0001" num="0000">The present invention, among other things, provides compounds, compositions and methods for treatment of cancer. In some embodiments, the present invention provides methods for treating blood cancer using agelastatin alkaloids.</p>
>> Read More

Methods of Treating Cancers, Immune and Autoimmune Diseases, and Inflammatory Diseases Based on BTK Occupancy and BTK Resynthesis Rate (Fri, 26 May 2017)
<p id="p-0001" num="0000">In an embodiment, therapeutic methods and uses of Bruton's Tyrosine Kinase (BTK) inhibitors for treatment of cancer, inflammation, immune disorders, and autoimmune disorders, including dermatoses, and for transplantation prophylaxis, based on BTK occupancies and/or BTK resynthesis rates for B cells in various diseases, tissue compartments, including bone marrow and lymph nodes, are described. In an embodiment, dosing regimens for a BTK inhibitor for treatment of cancer, inflammation, immune disorders, and autoimmune disorders, including dermatoses, and for transplantation prophylaxis, based on BTK occupancies and/or BTK resynthesis rates for B cells in various diseases, tissue compartments, including bone marrow and lymph nodes, are described.</p>
>> Read More

Piperidinone Derivatives as MDM2 Inhibitors for the Treatment of Cancer (Fri, 26 May 2017)
<p id="p-0001" num="0000">The present invention provides MDM2 inhibitor compounds of Formula I,</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.88mm" wi="32.43mm" file="US20170144971A1-20170525-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 the variables are defined above, which compounds are useful as therapeutic agents, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor.</li> </ul> </li> </ul> </p>
>> Read More

TRIPHENYLETHYLENE COMPOUNDS AND USES THEREOF (Fri, 26 May 2017)
<p id="p-0001" num="0000">Triphenylethylene compounds as dual aromatase inhibitors and selective estrogen receptors modulators are described. Also described are methods for treating patients of breast cancers, and patients of breast cancer comorbid with osteoporosis, using the described triphenylethylence compounds or pharmaceutical formulations thereof.</p>
>> Read More

LIN28/LET-7 CRYSTAL STRUCTURES, PURIFICATION PROTOCOLS, AND MOLECULAR PROBES SUITABLE FOR SCREENING ASSAYS AND THERAPEUTICS (Fri, 26 May 2017)
<p id="p-0001" num="0000">The invention provides compositions and methods for regulating microRNA (miRNA) biogenesis. The invention also relates to compositions and methods for treating or preventing cancer in a subject in need thereof.</p>
>> Read More

MARMELIN ANALOGS AND METHODS OF USE IN CANCER TREATMENT (Fri, 26 May 2017)
<p id="p-0001" num="0000">A pharmaceutical composition can include: a marmelin analog compound, and a pharmaceutically acceptable carrier having the compound. The compound can be present in a therapeutically effective amount to treat or inhibit a disease state. The disease state can be cancer. The cancer can be selected from brain cancers, head and neck cancers, thyroid cancers, gastrointestinal cancers, esophageal cancers, stomach cancers, pancreatic cancers, liver cancers, colo-rectal cancers, lung cancers, kidney cancers, prostate cancers, bladder cancers, testicular cancers, breast cancers, ovarian cancers, cervical cancers, and melanomas. The carrier includes a cyclodextrin, which may form a complex with the compound. The compounds and compositions can be used to treat or inhibit progression of cancers. Colorectal, bladder, and prostate cancers are examples of some of the cancers that can be treated with the marmelin analog compounds.</p>
>> Read More

HETEROCYCLIC INHIBITORS OF THE SODIUM CHANNEL (Fri, 26 May 2017)
<p id="p-0001" num="0000">The invention relates to compounds useful in treating conditions associated with voltage-gated ion channel function, particularly conditions associated with sodium channel activity. More specifically, the invention concerns heterocyclic compounds (e.g., compounds according to any of Formulas (1)-(11 1) or Compounds (1)-(65) of Table 1) that are that are useful in treatment of conditions such as epilepsy, cancer, pain, migraine, Parkinson's Disease, mood disorders, schizophrenia, psychosis, tinnitus, amyotropic lateral sclerosis, glaucoma, ischaemia, spasticity disorders, obsessive compulsive disorder, restless leg syndrome and Tourette syndrome.</p>
>> Read More

IMMUNOREGULATORY AGENTS (Fri, 26 May 2017)
<p id="p-0001" num="0000">Compounds that modulate the oxidoreductase enzyme indoleamine 2,3-dioxygenase, and compositions containing 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 indoleamine 2,3-dioxygenase is also provided.</p>
>> Read More

PHOSPHATE COMPOUNDS, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM (Fri, 26 May 2017)
<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="52.07mm" wi="69.85mm" file="US20170143746A1-20170525-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein X, Y, A<sub>1</sub>, A<sub>2</sub>, R<sub>a</sub>, R<sub>b</sub>, R<sub>c</sub>, R<sub>d</sub>, R<sub>3</sub>, R<sub>4</sub>, T and R<sub>5 </sub>are as defined in the description. Medicinal products containing the same which are useful in treating pathologies involving a deficit in apoptosis, such as cancer, auto-immune diseases, and diseases of the immune system.</p>
>> Read More

ANTI-TUMOR PHARMACEUTICAL APPLICATION OF PENTACYCLIC TRITERPENE SAPONIN COMPOUNDS OF SZECHUAN MELANDIUM ROOT (Fri, 26 May 2017)
<p id="p-0001" num="0000">The invention provides compounds of structural formula I or a salt thereof, and total saponins comprising such compounds in the preparation of anti-tumor agents. The present study of this invention showed that the compounds of formula I and the related total saponins had strong inhibitory effects on the proliferation of several human tumor cell lines, such as hepatocarcinoma, gastric cancer, colon cancer, breast cancer and melanoma cell lines, also the combination of structural formula I and the chemical agents could fairly well reduce toxicity and increase treatment effects.</p>
>> Read More

IMMUNE REGULATORY OLIGONUCLEOTIDE (IRO) COMPOUNDS TO MODULATE TOLL-LIKE RECEPTOR BASED IMMUNE RESPONSE (Fri, 26 May 2017)
<p id="p-0001" num="0000">The invention provides novel immune regulatory oligonucleotides (IRO) as antagonist of TLRs and methods of use thereof. These IROs have unique sequences that inhibit or suppress TLR-mediated signaling in response to a TLR ligand or TLR agonist. The methods may have use in the prevention and treatment of cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen.</p>
>> Read More

Method of treating cancer and gold(III) complexes as anti-cancer agents (Wed, 24 May 2017)
<p id="p-0001" num="0000">A method for treating cancer and gold(III) complexes with diaminocyclohexane ligand as anticancer agents. Also described are a pharmaceutical composition incorporating the gold(III) complexes and a method of synthesizing the gold(III) complexes.</p>
>> Read More

PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA) TARGETED NANOPARTICLES FOR THERAPY OF PROSTATE CANCER (Fri, 19 May 2017)
<p id="p-0001" num="0000">The invention provides a nanoparticle composition that is decorated with a urea-based small-molecule peptidomimetic inhibitor of prostate specific membrane antigen (PSMA), which is expressed by almost all solid tumors. This strategy takes advantage of both the avidity of the functionalized nanoparticle for binding to PSMA and the ability of the nanoparticle to be retained for longer periods of time in the tumor due to enhanced leakage via EPR into the tumor interstitium and poor clearance due to underdeveloped or non-existent lymphatics within the tumor.</p>
>> Read More

RIBONUCLEOTIDE REDUCTASE INHIBITORS AND METHODS OF USE (Fri, 19 May 2017)
<p id="p-0001" num="0000">Provided herein are novel compounds that inhibit ribonucleotide reductase (RR) by binding to RRM2 and interfering with the activity of the RRM1/RRM2 holoenzyme, as well as methods of synthesizing these novel compounds. The compounds may be used to inhibit RR activity and to treat various conditions associated with RRM2 expression, such as for example certain cancer types, mitochondrial diseases, or degenerative diseases.</p>
>> Read More

REGIOSELECTIVE N-2 ARYLATION OF INDAZOLES (Fri, 19 May 2017)
<p id="p-0001" num="0000">A novel process is provided for the efficient preparation of an asymmetric compound of structural formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.49mm" wi="65.19mm" file="US20170137403A1-20170518-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">comprising a copper-catalyzed, carbon-nitrogen cross-coupling step. The process described as part of the present invention can be used to manufacture poly (ADP-ribose) polymerase (PARP) inhibitors, which may be useful for the treatment of cancer. In particular, the present invention describes a process for the manufacture of the PARP inhibitor, 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide.</p>
>> Read More

FUSED CYCLOALKYL-PYRIMIDINE COMPOUNDS AND USES THEREOF (Fri, 19 May 2017)
<p id="p-0001" num="0000">Fused cycloalkyl-pyrimidine compounds that are kinase inhibitors, such as multi-kinase inhibitors, are provided. The compounds may be used in a method of treating cancer. Pharmaceutical compositions containing a fused cycloalkyl-pyrimidine compound and a pharmaceutically acceptable carrier are also provided, as are kits containing a fused cycloalkyl-pyrimidine compound or salt thereof and instructions for use, e.g., in a method of treating cancer.</p>
>> Read More

CATIONIC LIPID CORDIARIMIDE HYBRID COMPOUNDS AND A PROCESS FOR PREPARATION THEREOF (Fri, 19 May 2017)
<p id="p-0001" num="0000">The present invention relates to the cationic lipid cordiaroimide hybrid compounds of formula I. The present invention provides a process for preparation of these compounds is also being elaborated. The compounds described provides anticancerous activity against cell lines including PC-3 (prostate cancer), HepG2 (liver cancer), MCF-7 (breast cancer) and NIH-1/3T3 (non cancer cells. The compound was also capable of inducing caspase-3 mediated apoptosis in HepG2 cells by arresting the cell cycle in the G1 phase. Furthermore, the compound exhibited DNA ligase I inhibition. The present class of cationic lipid cordiarimide hybrids is likely to find specific use in developing novel targeted therapies for liver and prostate cancers.</p>
>> Read More

COMPOUNDS AND THEIR METHODS OF USE (Fri, 19 May 2017)
<p id="p-0001" num="0000">Compounds and compositions comprising compounds that inhibit glutaminase are described herein. Also described herein are methods of using the compounds that inhibit glutaminase in the treatment of cancer.</p>
>> Read More

SYNTHESIS OF HALICHONDRIN ANALOGS AND USES THEREOF (Fri, 19 May 2017)
<p id="p-0001" num="0000">The present invention provides halichondrin analogs, such as compounds of Formula (I). The compounds may bind to microtubule sites, thereby inhibiting microtubule dynamics. Also provided are methods of synthesis, pharmaceutical compositions, kits, methods of treatment, and uses that involve the compounds for treatment of a proliferative disease (e.g., cancer). Compounds of the present invention are particularly useful for the treatment of metastatic breast cancer, non-small cell lung cancer, prostate cancer, and sarcoma. The included methods of synthesis are useful for the preparation of compounds of Formula (I)-(III) along with naturally occurring halicondrins (e.g., halichondrin B & C, norhalichondrin A, B, & C, and homohalichondrin A, B, & C). Also included are methods for interconverting between the halichondrins, norhalichondrins, and homohalichondrins and their unnatural epimers at the C38 ketal stereocenter through the use of an acid-mediated equilibration.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="71.29mm" wi="76.20mm" file="US20170137437A1-20170518-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

FLAVAGLINE DERIVATIVES (Fri, 19 May 2017)
<p id="p-0001" num="0000">The invention relates to compounds of the following general formula (I) in the form of one of the enantiomers thereof or a mixture of the enantiomers thereof, and the pharmaceutically acceptable salts and/or solvates thereof, especially for the use thereof as a medicament, more specifically in cancer treatment. The invention also relates to pharmaceutical compositions containing same and to the methods for the production thereof.</p>
>> Read More

QUINOLIZINONE DERIVATIVES AS PI3K INHIBITORS (Fri, 19 May 2017)
<p id="p-0001" num="0000">Disclosed are compounds of formula (I), their tautomeric forms, stereoisomers, and pharmaceutically acceptable salts thereof, wherein R<sup>1</sup>-R<sup>4</sup>, and n are as defined in the specification, pharmaceutical compositions including a compound, tautomer, stereoisomer, or salt thereof, and methods of treating or preventing diseases or disorders, for example, cancer, that are amenable to treatment or prevention by inhibiting the PI3K enzyme of a subject.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="59.01mm" file="US20170137421A1-20170518-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

THERAPEUTIC USES OF SELECTED PYRROLOPYRIMIDINE COMPOUNDS WITH ANTI-MER TYROSINE KINASE ACTIVITY (Fri, 19 May 2017)
<p id="p-0001" num="0000">Uses of pyrrolopyrimidines with anti-Mer tyrosine kinase activity as anti-infective agents, immunostimulatory and immunomodulatory agents, anti-cancer agents (including against MerTK−/− tumors and ITD and TKD mutant forms of Acute Myeloid Leukemia (AML)), and as adjunctive agents in combination with chemotherapeutic, radiation or other standard of care for neoplasms.</p>
>> Read More

INHIBITORS OF LYSINE SPECIFIC DEMETHYLASE-1 (Fri, 19 May 2017)
<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

PLATINUM COMPLEXES AS ANTICANCER AGENTS (Fri, 19 May 2017)
<p id="p-0001" num="0000">Novel compounds comprising a Pt(II) metal center and S-containing ligands as anticancer agents including tetrakis(1,3-diazinane-2-thione)platinum(II) chloride monohydrate complex [Pt(Diaz)<sub>4</sub>]Cl<sub>2</sub>.H<sub>2</sub>O, wherein Diaz=1,3-diazinane-2-thione. Cytotoxic evaluations reveal that the compound possesses better cytotoxic activities against MCF7 than cisplatin. Methods of treating cancer comprising administering the compound are also provided.</p>
>> Read More

TARGETED THERAPEUTICS (Fri, 19 May 2017)
<p id="p-0001" num="0000">The present invention provides pharmacological compounds including a peptide epoxy ketone protease inhibitor conjugated to a binding moiety that directs the peptide epoxy ketone protease inhibitor to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and a peptide epoxy ketone protease inhibitor. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the peptide epoxy ketone protease inhibitor.</p>
>> Read More

CAR BASED IMMUNOTHERAPY (Fri, 19 May 2017)
<p id="p-0001" num="0000">The disclosure provides chimeric antigen receptors (CARs), T cells comprising such CARs, nucleic acids that encode such CARS, and methods of use thereof, e.g., to treat cancer such as B cell malignancies.</p>
>> Read More

DIARYLALKYLAMINE REV-ERB ANTAGONISTS AND THEIR USE AS MEDICAMENTS (Fri, 19 May 2017)
<p id="p-0001" num="0000">The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.97mm" wi="54.86mm" file="US20170136009A1-20170518-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">It further discloses a pharmaceutical composition comprising the compounds of Formula (I) and their uses as anti-proliferative and proapoptotic agents for cancer therapy.</p>
>> Read More

Therapeutic Combinations of a BTK Inhibitor, a PI3K Inhibitor and/or a JAK-2 Inhibitor (Fri, 19 May 2017)
<p id="p-0001" num="0000">Therapeutic combinations of a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms, are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of (1) a PI3K-δ inhibitor and a BTK inhibitor, (2) a JAK-2 inhibitor and a BTK inhibitor, or (3) a JAK-2 inhibitor, PI3K-δ inhibitor, and BTK inhibitor, and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.</p>
>> Read More

COMPOSITIONS AND METHODS FOR THE PRODUCTION OF PYRIMIDINE AND PYRIDINE COMPOUNDS WITH BTK INHIBITORY ACTIVITY (Fri, 19 May 2017)
<p id="p-0001" num="0000">The present invention provides novel pyrimidine and pyridine compounds according to Formula (I), Formula (II), Formula (III), Formula (IV) and Formula (V) their manufacture and use for the treatment of hyperproliferative diseases including, but not limited to, cancer, lupus, allergic disorders, Sjogren's disease and rheumatoid arthritis. In preferred embodiments, the present invention describes irreversible kinase inhibitors including, but not limited to, inhibitors of Bruton's tyrosine kinase.</p>
>> Read More

SELECTIVE ANDROGEN RECEPTOR DEGRADER (SARD) LIGANDS AND METHODS OF USE THEREOF (Fri, 19 May 2017)
<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

Chemokine CXCR4 and CCR5 Receptor Modulators and Uses Related Thereto (Fri, 19 May 2017)
<p id="p-0001" num="0000">The disclosure relates to chemokine receptor modulators and uses related thereto. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising compounds disclosed herein or pharmaceutically acceptable salts or prodrugs thereof. In certain embodiments, the compositions disclosed herein are used for managing chemokine related conditions, typically prevention or treatment of viral infections such as HIV or for managing cancer.</p>
>> Read More

SUBSTITUTED TRICYCLIC COMPOUNDS AS FGFR INHIBITORS (Fri, 19 May 2017)
<p id="p-0001" num="0000">The present invention relates to tricyclic compounds, 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.</p>
>> Read More

TREATMENT OF CANCERS RELATED TO CHRONICALLY ACTIVE RAS (Fri, 19 May 2017)
The present invention discloses that naphthofuranquinones and dihydroxynaphthofurans, and derivatives thereof, such as a compound of formula (I) or (II), are effective in deactivating chronically active Ras. The present invention also discloses a method of treating or preventing cancer comprising steps of: 1) identifying a patient suffering from or susceptible to a cancer related to chronically active Ras; and 2) administering a therapeutically effective amount of a compound of formula (I) or (II), or a pharmaceutically acceptable salt thereof. The present invention further discloses a method of treating or preventing cancer comprising steps of: 1) identifying a patient suffering from or susceptible to a cancer related to a K-Ras mutation; and 2) administering a therapeutically effective amount of a compound of formula (I) or (II), or a pharmaceutically acceptable salt thereof.
>> Read More

TETRAHYDROPALMATINE DERIVATIVE, ITS PREPARATION METHOD AND USE (Fri, 19 May 2017)
Provided a compound of formula (I): or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and the compound is tetrahydropalmatine derivative. The compound has a use in preparation of a medicament, and the medicament is used for inhibiting proliferation of a cancer cell of a eukaryote and/or treating or preventing cancer.
>> Read More

GLYPICAN 2 AS A CANCER MARKER AND THERAPEUTIC TARGET (Fri, 19 May 2017)
The present disclosure is directed to antibodies binding to Glypican 2 and methods of using such antibodies to treat cancers that express or overexpress the Glypican 2 antigen.
>> Read More

DIHYDROIMIDAZOPYRAZINONE DERIVATIVES USEFUL IN THE TREATMENT OF CANCER (Fri, 19 May 2017)
The present disclosure concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R1, R2 and R3 have any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cancer.
>> Read More

BIARYL COMPOUNDS AS ANTIMICROBIAL AND CHEMOTHERAPEUTIC AGENTS (Fri, 19 May 2017)
In one aspect, the present disclosure provides diaryl compounds of the formula presented herein. The application also provides compositions and methods of treatment thereof. In some embodiments, these compounds are used in the treatment of bacterial infections or in the treatment of cancer.
>> Read More

DIHYDROPYRROLOPYRAZINONE DERIVATIVES USEFUL IN THE TREATMENT OF CANCER (Fri, 19 May 2017)
The invention concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R1 has any of the meanings hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cancer.
>> Read More

SUBSTITUTED 2-THIOXO-IMIDAZOLIDIN-4-ONES AND SPIRO ANALOGUES THEREOF, ACTIVE ANTI-CANCER INGREDIENT, PHARMACEUTICAL COMPOSITION, MEDICINAL PREPARATION, METHOD FOR TREATING PROSTATE CANCER (Thu, 18 May 2017)
The invention relates to novel ( R )-stereoisomers of substituted 2-thioxo-imidazolidin-4-ones of formula 1 , or spiro analogues thereof, which exhibit androgen receptor antagonist properties, variants of a method for producing the same, and intermediate compounds for producing compounds of formula 1 . Compounds of formula 1 can be used to produce a medicinal agent suitable for treating cancers, such as prostate cancer and breast cancer. The invention also relates to a pharmaceutical composition in the form of tablets, capsules, injections. In formula 1 wherein R1 is OH, NH 2 , or an OR4 group; R2 and R3 are methyl, or R2 and R3 are a CH 2 -CH 2 group; R4 is C 1 -C 4 alkyl or cyclopropyl.
>> Read More

Method for treating prostate cancer and/or gastrointestinal cancer (Wed, 17 May 2017)
<p id="p-0001" num="0000">Gold(III) complexes having mixed ligands as anticancer agents. The gold(III) complexes are coordinated to bidentate ligands having diamino functional groups: a diaminocyclohexane ligand and an ethylenediamine ligand. These complexes can exist in both cis- and trans-configurations. Also described are pharmaceutical compositions incorporating the gold(I) complexes, methods of synthesis, methods of treating cancer and methods of inhibiting cancer cell proliferation and inducing cancer cell apoptosis.</p>
>> Read More

Heterocycle-substituted pyridyl benzothiophenes as kinase inhibitors (Wed, 17 May 2017)
<p id="p-0001" num="0000">This invention is directed to a compound of Formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.96mm" wi="66.38mm" file="US09650366-20170516-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> or a pharmaceutically acceptable salt thereof, wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and X are as defined herein. The compounds of Formula I are useful as receptor tyrosine kinase (RTK) inhibitors and can be used to treat such diseases as cancer, blood vessel proliferative disorders, fibrotic disorders, mesangial cell proliferative disorders and metabolic diseases. </p>
>> Read More

Salicylic acid derivatives, pharmaceutically acceptable salt thereof, composition thereof and method of use thereof (Wed, 17 May 2017)
<p id="p-0001" num="0000">The present invention relates to novel compounds, compositions containing same and methods for inhibiting STAT3 and/or STAT5 activity or for the treatment of a STAT3 or STAT5-dependent cancer using said compounds; or a pharmaceutically acceptable salt, solvate or prodrug thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="19.30mm" wi="36.58mm" file="US09650399-20170516-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

TUMOR SUPPRESSOR AND ONCOGENE BIOMARKERS PREDICTIVE OF ANTI-IMMUNE CHECKPOINT INHIBITOR RESPONSE (Fri, 12 May 2017)
<p id="p-0001" num="0000">The present invention is based on the identification of novel biomarkers predictive of responsiveness to anti-immune checkpoint inhibitor therapies.</p>
>> Read More

Pharmaceutical Compositions and Methods (Fri, 12 May 2017)
<p id="p-0001" num="0000">This invention relates the use of cortisol blockers (e.g., glucocorticoid receptor [GR] antagonists) for the treating or preventing viral infections, treating or preventing treatment resistant prostate cancer, treating or preventing neoplasia, and treating or preventing infection related to acute or chronic injury or disease.</p>
>> Read More

METHOD FOR TREATING CANCER USING CHEMOKINE ANTAGONISTS (Fri, 12 May 2017)
<p id="p-0001" num="0000">What is described is a method for treating cancer in a patient in need of such treatment through the use of an antagonist to CXCR1 and/or CXCR2 receptors by administering a therapeutically effective amount of an antagonist of CXCR1 and/or CXCR2, or pharmaceutical compositions thereof, either alone as monotherapy, or in combination with at least one other anticancer therapy.</p>
>> Read More

FAP-Activated Therapeutic Agents, and Uses Related Thereto (Fri, 12 May 2017)
<p id="p-0001" num="0000">Disclosed are prodrugs of anthracyclines (such as doxorubicin) and derivatives thereof that are selectively cleaved and activated by fibroblast activating protein (FAP). The prodrugs are useful for targeted delivery of “warhead” anthracycline or anthracycline derivative to FAP-expressing tissues, including cancer (e.g., solid tumors). Also provided are pharmaceutical compositions comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation, e.g., cancer, undesirable fibrosis, and undesirable inflammation.</p>
>> Read More

PHARMACEUTICAL COMPOSITIONS COMPRISING POH DERIVATIVES (Fri, 12 May 2017)
<p id="p-0001" num="0000">The present invention provides for a derivative of monoterpene or sesquiterpene, such as a perillyl alcohol derivative. For example, the perillyl alcohol derivative may be a perillyl alcohol carbamate. The perillyl alcohol derivative may be perillyl alcohol conjugated with a therapeutic agent such as a chemotherapeutic agent. The present invention also provides for a method of treating a disease such as cancer, comprising the step of delivering to a patient a therapeutically effective amount of a derivative of monoterpene (or sesquiterpene). The route of administration may vary, and can include, inhalation, intranasal, oral, transdermal, intravenous, subcutaneous or intramuscular injection.</p>
>> Read More

TARGETED THERAPEUTICS (Fri, 12 May 2017)
<p id="p-0001" num="0000">The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.</p>
>> Read More

TARGETED POLYMERIC NANO-COMPLEXES AS DRUG DELIVERY SYSTEM (Fri, 12 May 2017)
<p id="p-0001" num="0000">The present invention provides targeted polymeric nano-complexes for delivery of drugs such as anti-mitotic agents or anti-cancer agents. The present invention also provides a process for the preparation of such targeted nano-complexes.</p>
>> Read More

LSD1 Inhibitors (Fri, 12 May 2017)
<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

Pyrazolopyrimidine Derivatives Useful as Inhibitors of Bruton's Tyrosine Kinase (Fri, 12 May 2017)
<p id="p-0001" num="0000">This invention relates to compounds of formula (I). The compounds of the invention are tyrosine kinase inhibitors. Specifically, the compounds of the invention are useful as inhibitors of Bruton's tyrosine kinase (BTK). The invention also contemplates the use of the compounds for treating conditions treatable by the inhibition of Bruton's tyrosine kinase, for example cancer, lymphoma, leukemia and immunological diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.09mm" wi="69.68mm" file="US20170129897A1-20170511-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

NANOPARTICLES CONTAINING AZOLIUM AND N-HETEROCYCLIC CARBENE COMPOUNDS AND USE THEREOF (Fri, 12 May 2017)
<p id="p-0001" num="0000">The present application provides a composition comprising a core formed by gold nanoparticle, a compound of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.40mm" wi="62.82mm" file="US20170129907A1-20170511-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein dashed lines in Formula (I) represent (i) with or without an attachment of benzol group, (ii) a delocalized bond where shown within a ring; R<sub>1 </sub>is hydrogen or a halogen; R<sub>2 </sub>is a linker selected from C<sub>6-20 </sub>alkyl or polyethylene glycol; R<sub>3 </sub>is C<sub>1-20 </sub>alkyl, C<sub>1-20 </sub>substituted alkyl, hexadecanyl amido, pyridinyl, benzyl or pyrimidinyl; and a compound of Formula (II):</p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="66.72mm" wi="63.25mm" file="US20170129907A1-20170511-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005" num="0000">wherein dashed lines, R<sub>1</sub>, R<sub>2 </sub>and R<sub>3 </sub>are defined as in Formula (II), and M is a metal. The composition has an inhibition ability against a cancer.</p>
>> Read More

H. Pylori Lipopolysaccharide Outer Core Epitope (Fri, 12 May 2017)
<p id="p-0001" num="0000"><i>Helicobacter pylori</i>, one of the most common human pathogens, is associated with the development of human chronic gastritis, peptic ulcers and gastric cancer. The invention relates to a α1,6-glucan-containing <i>Helicobacter pylori </i>compound comprising the structure of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.23mm" wi="76.20mm" file="US20170129941A1-20170511-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R is a α-DDHep-3-α-L-Fuc-3-β-GlcNAc trisaccharide substituted with an α1,6-glucan linked to an α1,3-DD-heptan, and wherein the last DD-Hep residue of α1,3-DD-heptan is capped with β-GlcNAc residue. Compositions comprising the compound, uses of the compound, and antibodies raised against the compound are also described.</p>
>> Read More

METHODS OF TREATING ANDROGEN RECEPTOR-MEDIATED DISORDERS WITH IMIDAZOLINE DERIVATIVES (Fri, 12 May 2017)
<p id="p-0001" num="0000">Methods for treating androgen receptor-mediated diseases, such as breast cancer, with imidazoline derivatives of formula (I) are provided:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.79mm" wi="67.90mm" file="US20170128422A1-20170511-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Cyclic Amine Azaheterocyclic Carboxamides (Fri, 12 May 2017)
<p id="p-0001" num="0000">The invention provides novel cyclic amine azaheterocyclic carboxamide according to Formula (I), Formula (II) and Formula (III) their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.</p>
>> Read More

INHIBITORS OF LYSINE SPECIFIC DEMETHYLASE-1 (Fri, 12 May 2017)
<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

HETEROCYCLIC COMPOUNDS AS PI3K-y INHIBITORS (Fri, 12 May 2017)
<p id="p-0001" num="0000">This application relates to compounds of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="54.95mm" wi="58.59mm" file="US20170129899A1-20170511-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salts or stereoisomers thereof, which are inhibitors of PI3K-γ which are useful for the treatment of disorders such as autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.</p>
>> Read More

NEW COMPOUND FOR INHIBITING BINDING BETWEEN DX2 PROTEIN AND P14/ARF PROTEIN, AND PHARMACEUTICAL COMPOSITION FOR TREATING OR PREVENTING CANCER DISEASE CONTAINING SAME AS EFFECTIVE INGREDIENT (Fri, 12 May 2017)
<p id="p-0001" num="0000">Disclosed is a new compound that inhibits binding between a DX2 protein and a p14/ARF protein, a pharmaceutical composition including the new compound as an effective component for treating or preventing a cancer disease, an anticancer adjuvant for improving an anticancer effect of a drug-resistant anticancer drug, and a composition including an AIMP2-DX2 protein or a fragment thereof for diagnosing lung cancer.</p>
>> Read More

Humanized Anti-Epiregulin Antibody, and Cancer Therapeutic Agent Comprising Said Antibody as Active Ingredient (Fri, 12 May 2017)
<p id="p-0001" num="0000">The inventors successfully produced anti-Epiregulin antibodies showing cross-species reactivity between cynomolgus monkey (non-human animals) and human, anti-Epiregulin antibodies with suppressed chemical degradation, anti-Epiregulin antibodies with lowered isoelectric point, anti-Epiregulin antibodies with increased thermal denaturation midpoint temperature, and anti-Epiregulin antibodies with reduced amount of aggregate by performing appropriate amino acid residue substitutions in the variable-region sequences of the humanized EP27 antibody which inhibits growth of cancer cells by exhibiting cytotoxic activity and neutralizing activity against human Epiregulin-expressing cells.</p>
>> Read More

IMIDAZO[4,5-C]QUINOLIN-2-ONE COMPOUNDS AND THEIR USE IN TREATING CANCER (Fri, 12 May 2017)
The specification generally relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof, where x, R1, R2, R3, R4 and R5 have any of the meanings defined herein. The specification also relates to the use of compounds of Formula (I) and salts thereof to treat or prevent ATM mediated disease, including cancer. The specification further relates to pharmaceutical compositions comprising substituted imidazo[4,5-c]quinolin-2-one compounds and pharmaceutically acceptable salts thereof; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; and intermediates useful in such manufacture.
>> Read More

ROR GAMMA AGONISTS AS ENHANCERS OF PROTECTIVE IMMUNITY (Fri, 12 May 2017)
The T cell specific RORgamma isoform RORgammat has been shown to be the key lineage-defining transcription factor to initiate the differentiation program of TH17 and TC17 cells, cells that have demonstrated anti-tumor efficacy, RORgammat controls gene networks that enhance immunity including increased IL17 production and decreased immune suppression. Agonists of RORgammat have been shown to increase the basal activity of RORgammat enhancing TH17 cell proliferation. Here we show that activation of RORgammat using synthetic agonists drives proliferation of TH17 cells while decreasing levels of the immune checkpoint protein PD-1, a mechanism that should enhance anti-tumor immunity while blunting tumor associated adaptive immune resistance. Interestingly, putative endogenous agonists drive proliferation of TH17 cells but do not repress PD-1. These findings suggest that synthetic agonists of RORgammat should activate Tc17/TH17 cells, decrease the population of Tregs, repress PD-1, and produce IL17 in situ, an immune factor associated with good prognosis in cancer.
>> Read More

THERAPY AND PHARMACEUTICAL COMPOSITION (Fri, 12 May 2017)
A novel class of compounds called perenosins, and their use in the treatment and/or prevention of cancer or a neoplastic condition.
>> Read More

SELECTIVE HDAC8 INHIBITORS AND THEIR USES (Fri, 12 May 2017)
The present invention relates to small molecule compounds based on benzopyrimido- or benzoimidazo-thiazin-imine as well as their (synthesis) intermediates and their use as HDAC inhibitors, in particular HDAC8 inhibitors. The present invention also relates to the use of said compounds in the treatment of cancer and as therapeutic agents for eukaryotic parasites and respective methods of treatment.
>> Read More

TETRAHYDROINDAZOLES AND MEDICAL USES THEREOF (Fri, 12 May 2017)
There is herein provided a compound of formula I (I) or a pharmaceutically acceptable salt thereof, for use in the treatment of cancer and/or the treatment or prevention of a viral infection, wherein A1, A2, L1, R1, R2 and n have meanings as provided in the description.
>> Read More

1,4-DICARBONYL-PIPERIDYL DERIVATIVES (Fri, 12 May 2017)
Compounds of the formula I in which Z, W, Q, R and Y have the meanings indicated in Claim 1, are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.
>> Read More

IMIDAZO[4,5-C]QUINOLIN-2-ONE COMPOUNDS AND THEIR USE IN TREATING CANCER (Fri, 12 May 2017)
The specification generally relates to compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, where R1, R2, R3 and R4 have any of the meanings defined herein. The specification also relates to the use of compounds of Formula (I) and salts thereof to treat or prevent ATM mediated disease, including cancer. The specification further relates to pharmaceutical compositions comprising substituted imidazo[4,5-c]quinolin-2-one compounds and pharmaceutically acceptable salts thereof; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; and intermediates useful in such manufacture.
>> Read More

LSD1 INHIBITORS (Fri, 12 May 2017)
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.
>> Read More

HETERO-SUBSTITUTED CYCLIC LACTONE ANALOGUES AND USES THEREOF (Fri, 12 May 2017)
The present disclosure provides SL and SL derivatives comprising a polar substituent adjacent to the lactone ring. Additionally, the present disclosure provides methods of using the SL and SL derivatives to inhibit the growth of leukemic cancer cells.
>> Read More

HETEROCYCLIC COMPOUNDS AS PI3K-GAMMA INHIBITORS (Fri, 12 May 2017)
This application relates to compounds of Formula (I): or pharmaceutically acceptable salts or stereoisomers thereof, which are inhibitors of PI3K-γ which are useful for the treatment of disorders such as autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.
>> Read More

BIOLOGICALLY ACTIVE OLIGONUCLEOTIDES CAPABLE OF MODULATING THE IMMUNE SYSTEM (Thu, 11 May 2017)
The present invention relates to methods of identifying oligonucleotides capable of modulating the immune system in a mammalian subject, comprising analysis of which tertiary structural type said oligonucleotide adopts, in phosphate-buffered saline solution. Further, the invention provides oligonucleotides identifiable by the methods of the invention and to their use in methods of treating diseases, such as inflammatory diseases, autoimmune diseases, infectious diseases, neurodegenerative diseases and cancer.
>> Read More

SUBSTITUTED BENZENE COMPOUNDS (Thu, 11 May 2017)
The present invention relates to substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and such compounds for use in treating cancer. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.
>> Read More

CHLOROTOXIN VARIANTS, CONJUGATES AND METHODS FOR THEIR USE (Thu, 11 May 2017)
Chlorotoxin variants, chlorotoxin variant conjugates, compositions that include the chlorotoxin variants or conjugates, and methods for using the chlorotoxin variants, conjugates, and compositions. In particular, conjugates comprising a chlorotoxin variant where lysine K15 and/or lysine K23 are substituted by other amino acids, coupled to a fluorescent label.
>> Read More

METHODS FOR THE DIAGNOSIS OF COLORECTAL CANCER AND OVARIAN CANCER HEALTH STATES (Thu, 11 May 2017)
The present invention relates to the diagnosis of colorectal and ovarian cancers (CRC and OC, respectively). The present invention describes the relationship between endogenous small molecules and CRC or OC. Specifically, the present invention relates to the diagnosis of CRC and OC through the measurement of vitamin E isoforms and related metabolites. The present invention also relates to diagnostic markers identified in said method. The present invention relates to the underlying case and pre-symptomatic phases of CRC, the diagnosis of various stages and severity of CRC, the early detection of CRC, monitoring and diagnosing the effect of therapy on CRC and OC health states.
>> Read More

Combinational compositions and methods for treatment of cancer (Wed, 10 May 2017)
<p id="p-0001" num="0000">The present invention provides methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of a pyrroloquinolinyl-pyrrole-2,5-dione compound or a pyrroloquinolinyl-pyrrolidine-2,5-dione compound in combination with a therapeutically effective amount of a second anti-proliferative agent.</p>
>> Read More

2- (AZAINDOL-2-YL) BENZIMIDAZOLES AS PAD4 INHIBITORS (Fri, 05 May 2017)
<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="27.86mm" wi="73.24mm" file="US20170119750A1-20170504-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">R<sub>1 </sub>is hydrogen or C<sub>1-6</sub>alkyl;</li> <li id="ul0002-0002" num="0000">R<sub>2 </sub>is hydrogen, C<sub>1-6</sub>alkyl, perhalomethylC<sub>0-5</sub>alkyl-O—, or C<sub>1-6</sub>alkoxy;</li> <li id="ul0002-0003" num="0000">R<sub>3 </sub>is hydrogen, C<sub>1-6</sub>alkyl, or C<sub>1-6</sub>alkoxyC<sub>1-6</sub>alkyl;</li> <li id="ul0002-0004" num="0000">R<sub>4 </sub>is hydrogen, C<sub>1-6</sub>alkyl, perhalomethylC<sub>1-6</sub>alkyl; or unsubstituted C<sub>3-6</sub>cycloalkylC<sub>1-6</sub>alkyl;</li> <li id="ul0002-0005" num="0000">A is C—R<sub>5 </sub>or N;</li> <li id="ul0002-0006" num="0000">B is C—R<sub>6 </sub>or N;</li> <li id="ul0002-0007" num="0000">D is C—R<sub>7 </sub>or N;</li> <li id="ul0002-0008" num="0000">with the proviso that at least one of A, B, and D, is N;</li> <li id="ul0002-0009" num="0000">R<sub>5 </sub>is hydrogen or C<sub>1-6</sub>alkyl;</li> <li id="ul0002-0010" num="0000">R<sub>6 </sub>is hydrogen or C<sub>1-6</sub>alkyl;</li> <li id="ul0002-0011" num="0000">R<sub>7 </sub>is hydrogen, C<sub>1-6</sub>alkyl, C<sub>1-6</sub>alkoxy, or hydroxy;</li> <li id="ul0002-0012" num="0000">R<sub>8 </sub>is hydrogen or C<sub>1-6</sub>alkyl, with the proviso that one of R<sub>4 </sub>and R<sub>8 </sub>is hydrogen;</li> <li id="ul0002-0013" num="0000">R<sub>9 </sub>is hydrogen or hydroxy;</li> <li id="ul0002-0014" num="0000">R<sub>10 </sub>is hydrogen or C<sub>1-6</sub>alkyl; <br/> and salts thereof are PAD4 inhibitors and may be useful in the treatment of various disorders, for example rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosis, and psoriasis. </li> </ul> </li> </ul> </p>
>> Read More

ARYL- OR HETEROARYL-SUBSTITUTED BENZENE COMPOUNDS (Fri, 05 May 2017)
<p id="p-0001" num="0000">The present invention relates to aryl- or heteroaryl-substituted benzene 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

DENDRIMER COMPOSITIONS AND USE IN TREATMENT OF NECROTIZING ENTEROCOLITIS AND OTHER GASTROINTESTINAL DISORDERS (Fri, 05 May 2017)
<p id="p-0001" num="0000">A dendrimer formulation, such as a PAMAM dendrimer or a multiarm PEG polymeric formulation has been developed for oral administration to the gastrointestinal tract for treatment of inflammatory diseases associated with infection or cancer. In the preferred embodiment, the dendrimers are in the form of dendrimer nanoparticles comprising poly(amidoamine) (PAMAM) hydroxyl-terminated dendrimers covalently linked to at least one therapeutic, prophylactic or diagnostic agent for treatment of one or more symptoms of necrotizing enterocolitis.</p>
>> Read More

HETEROCYCLIC MODULATORS OF LIPID SYNTHESIS (Fri, 05 May 2017)
<p id="p-0001" num="0000">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).</p>
>> Read More

PH-SENSITIVE AND BIOREDUCIBLE POLYMER-VIRUS COMPLEX FOR CANCER TREATMENT (Fri, 05 May 2017)
<p id="p-0001" num="0000">The present invention relates to a pH-sensitive and bioreducible polymer-virus complex which can destroy tumor cells more effectively by increasing the efficiency of virus transduction, to a pH-sensitive and bioreducible polymer, and to a pharmaceutical composition containing the polymer-virus complex.</p>
>> Read More

PHARMACEUTICAL COMPOSITIONS COMPRISING POH DERIVATIVES (Fri, 05 May 2017)
<p id="p-0001" num="0000">The present invention provides for a derivative of monoterpene or sesquiterpene, such as a perillyl alcohol derivative. For example, the perillyl alcohol derivative may be a perillyl alcohol carbamate. The perillyl alcohol derivative may be perillyl alcohol conjugated with a therapeutic agent such as a chemotherapeutic agent. The present invention also provides for a method of treating a disease such as cancer, comprising the step of delivering to a patient a therapeutically effective amount of a derivative of monoterpene for sesquiterpene). The route of administration may vary, and can include, inhalation, intranasal, oral, transdermal, intravenous, subcutaneous or intramuscular injection.</p>
>> Read More

AMORPHOUS SOLID FORM OF A BET PROTEIN INHIBITOR (Fri, 05 May 2017)
<p id="p-0001" num="0000">The present invention relates to an amorphous solid form of (4S)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one, and processes for its preparation, which is an inhibitor of BET proteins such as BRD2, BRD3, BRD4, and BRD-t and is useful in the treatment of various diseases such as cancer.</p>
>> Read More

Molecular Analysis of Tumor Samples (Fri, 05 May 2017)
<p id="p-0001" num="0000">This invention relates to methods for diagnosing cancer, e.g., cancer of epithelial origin, by detecting the presence of tumor cells in a sample, based (at least in some embodiments) on the quantification of levels of four biomarkers, MUC1, EGFR, EpCAM, and HER2. In some embodiments, the methods are performed using diagnostic magnetic resonance (DMR), e.g., with a portable relaxometer or MR imager.</p>
>> Read More

SALTS OF A PIM KINASE INHIBITOR (Fri, 05 May 2017)
<p id="p-0001" num="0000">The present invention relates to salt forms of the Pim kinase inhibitor N-{(7R)-4-[(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-6-(2,6-difluorophenyl)-5-fluoropyridine-2-carboxamide, including methods of preparation thereof, and intermediates in the preparation thereof, where the compound is useful in the treatment of Pim kinase-related diseases such as cancer.</p>
>> Read More

Selective androgen receptor modulators (Fri, 05 May 2017)
<p id="p-0001" num="0000">This invention provides compounds of Formula (II), or (IIa) and or salts thereof, pharmaceutical compositions comprising a compound of Formula (II), or (IIa) and a pharmaceutically acceptable excipient, processes for making compounds for Formula (II), or (IIa) and intermediates useful in the preparation of same; and methods of modulating the androgen receptor, methods of treating diseases beneficially treated by an androgen receptor modulator (e.g., sarcopenia, prostate cancer, contraception, type II diabetes related disorders or diseases, anemia, depression, and renal disease) using compounds of Formula (I), (II), or (IIa).</p>
>> Read More

DIPEPTIDES AS INHIBITORS OF HUMAN IMMUNOPROTEASOMES (Fri, 05 May 2017)
<p id="p-0001" num="0000">The compounds of the present invention are represented by the following compounds having Formula (I) where the substituents R<sup>1</sup>-R<sup>10</sup>, X, Y, k, m, n, q, and s are as defined herein. These compounds are used in the treatment of cancer, immunologic disorders, autoimmune disorders, neurodegenerative disorders, or inflammatory disorders or for providing immunosuppression for transplanted organs or tissues.</p>
>> Read More

ANTIBODY CONJUGATES COMPRISING TOLL-LIKE RECEPTOR AGONIST (Fri, 05 May 2017)
<p id="p-0001" num="0000">Provided herein are antibody conjugates comprising toll-like receptor agonists and the use of such conjugates for the treatment of cancer. In some embodiments, the conjugates comprise anti-HER2 antibodies.</p>
>> Read More

COMPOSITIONS AND METHODS FOR CHARACTERIZING, REGULATING, DIAGNOSING, AND TREATING CANCER (Fri, 05 May 2017)
<p id="p-0001" num="0000">The present invention relates to compositions and methods for characterizing, regulating, diagnosing, and treating cancer. For example, the present invention provides compositions and methods for inhibiting tumorigenesis of certain classes of cancer cells, including breast cancer cells and preventing metastasis. The present invention also provides systems and methods for identifying compounds that regulate tumorigenesis.</p>
>> Read More

DIGLYCIDIC ETHER DERIVATIVE THERAPEUTICS AND METHODS FOR THEIR USE (Fri, 05 May 2017)
<p id="p-0001" num="0000">This invention provides compound having a structure of Formula I or Formula II. Uses of such compounds for treatment of various indications, including prostrate cancer as well as methods of treatment involving such compounds are also provided.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="74.25mm" wi="69.93mm" file="US20170121261A1-20170504-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

USE OF A NOVEL 3-ARYL-4-CATECHOL-PYRROLE-N-PROPANOL COMPOUND AND THE DERIVATIVES THEREOF TO TREAT CANCER AND DISEASES RELATED TO EXCESSIVE ANGIOGENESIS (Fri, 05 May 2017)
<p id="p-0001" num="0000">The present invention relates to a 3-aryl-4 catechol-pyrrole-n-propanol compound and the derivatives thereof having General Formula (I), wherein:—R<sup>1 </sup>is an aryl group, particularly a phenyl, optionally substituted by one or more (C<sub>1</sub>-C<sub>2</sub>)alkyl groups one or more halogens, one or more —OH, —CN or CF<sub>3 </sub>groups, or a combination of same, and—R<sup>2 </sup>is a (C<sub>1</sub>-C<sub>2</sub>)alkyl group, a hydroxy(C<sub>1</sub>-C<sub>8</sub>)alkyl group, a (C<sub>1</sub>-C<sub>4</sub>)alocoxy(C<sub>1</sub>-C<sub>8</sub>)alkyl group, or a pharmaceutically acceptable hydrate or solvate of same. The invention also relates to the methods for preparing said compound and derivatives, to the pharmaceutical compositions containing same, and to the use of same as a drug or in the form of a prodrug converted via dimerization, particularly via oxidative coupling in the presence of a superoxide anion, in the treatment of cancer and diseases related to excessive angiogenesis.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.95mm" wi="69.85mm" file="US20170121283A1-20170504-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

COMPOSITIONS AND METHODS FOR INHIBITING ARGINASE ACTIVITY (Fri, 05 May 2017)
<p id="p-0001" num="0000">The invention relates to a novel class of compounds that exhibit activity inhibitory activity toward arginase, and pharmaceutical compositions comprising the compounds of the invention. Also provided herein are methods of treating cancer with the arginase inhibitors of the invention.</p>
>> Read More

HISTONE ACETYLTRANSFERASE MODULATORS AND USES THEREOF (Fri, 05 May 2017)
<p id="p-0001" num="0000">The invention provides compounds and compositions comprising compounds that modulate histone acyl transferase (HAT). The invention further provides methods for treating neurodegenerative disorders, conditions associated with accumulated amyloid-beta peptide deposits, Tau protein levels, and/or accumulations of alpha-synuclein as well as cancer by administering a compound that modulates HAT to a subject.</p>
>> Read More

NOVEL COMPOUNDS COMPRISING A BOMBESIN DERIVATIVE, A PROCESS FOR THE PREPARATION THEREOF AND A NUCLEAR MOLECULAR IMAGING AGENT COMPRISING THE SAME (Fri, 05 May 2017)
<p id="p-0001" num="0000">Provided are a novel compound, in which a bombesin derivative known as having selectivity with respect to prostate cancer bonds with a ligand via aminomethyl galacturonic acid, a complex compound that covalently bonds with a radioactive isotope via the ligand of the novel compound, methods of preparing the compounds, and a nuclear-based molecular imaging agent including the complex compound.</p>
>> Read More

A THERAPEUTIC PROTOCOL FOR TREATING OVARIAN CANCER (Fri, 05 May 2017)
<p id="p-0001" num="0000">The present invention is directed to a pharmaceutical combination for treating proliferative disease comprising a compound of formula (I), or a salt, solvate or prodrug thereof, carboplatin or cisplatin, and gemcitabine. The present invention is further directed to a therapeutic protocol to manage ovarian cancer treatment in a female subject involving the administration of the combination to an ovarian cancer subject with recurrent or persistent ovarian cancer following treatment with platinum-based therapy. Kits comprising the combination as well as the use of the combination in the treatment of a proliferative disease are further contemplated.</p>
>> Read More

AURORA A KINASE INHIBITOR (Fri, 05 May 2017)
<p id="p-0001" num="0000">The present invention provides an aminopyridine compound, or a pharmaceutically acceptable salt thereof, that inhibits Aurora A and, therefore may be useful in treating cancer.</p>
>> Read More

COMBINATIONS (Fri, 05 May 2017)
<p id="p-0001" num="0000">The invention relates to a combination of a first compound selected from N-(3,5-dimethoxyphenyl)-N′-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine or a pharmaceutically acceptable salt thereof or a solvate thereof, and N-(2-fluoro-3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-3-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazin-6-amine or a pharmaceutically acceptable salt thereof or a solvate thereof; and a second compound which is a cMet inhibitor. The combination is for use in the treatment of a proliferative disorder, in particular for use in the treatment of cancer. The FGFR inhibitor (N-(3,5-dimethoxyphenyl)-N′-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine or a pharmaceutically acceptable salt thereof or a solvate thereof, and N-(2-fluoro-3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-3-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazin-6-amine or a pharmaceutically acceptable salt thereof or a solvate thereof) and the cMet inhibitor can be administered simultaneously, separately or sequentially. The invention further relates to a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a combination according to the invention.</p>
>> Read More

BICYCLIC HETEROCYCLES AS FGFR4 INHIBITORS (Fri, 05 May 2017)
<p id="p-0001" num="0000">The present disclosure relates to bicyclic heterocycles, and pharmaceutical compositions of the same, that are inhibitors of the FGFR4 enzyme and are useful in the treatment of FGFR4-associated diseases such as cancer.</p>
>> Read More

NOVEL GLUCOSE DERIVATIVE, AND CELL IMAGING METHOD AND IMAGING AGENT USING SAID DERIVATIVE (Fri, 05 May 2017)
<p id="p-0001" num="0000">Provided is a glucose derivative, which is taken into cells via a membrane sugar transport system and is represented by formula (1). Also provided are an imaging agent and an imaging method for a cell or intracellular molecule using said glucose derivative. Further provided are a method for detecting cancer cells with good accuracy using said glucose derivative and an imaging agent to be used in said method. More specifically provided are D-glucose derivatives and L-glucose derivatives in which glucose is bound to the 7-position of a fluorescent molecular group with a coumarin backbone or a quinolone backbone. Also provided are a cell imaging agent and imaging method using the derivative. A cancer cell imaging agent and imaging method using the L-glucose derivative is also provided. G is a group selected from formulas (G1)-(G4) below.</p>
>> Read More

CYCLOPROPYLAMINES AS LSD1 INHIBITORS (Fri, 05 May 2017)
<p id="p-0001" num="0000">The present invention is directed to cyclopropylamine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.</p>
>> Read More

HETEROCYCLIC MODULATORS OF HIF ACTIVITY FOR TREATMENT OF DISEASE (Fri, 05 May 2017)
<p id="p-0001" num="0000">The present invention relates to compounds and methods which may be useful as inhibitors of HIF pathway activity for the treatment or prevention of cancer and other hypoxia-mediated diseases.</p>
>> Read More

FUSION MOLECULE BASED ON NOVEL TAA VARIANT (Fri, 05 May 2017)
<p id="p-0001" num="0000">This invention provides novel carbonic anhydrase (CAIX) nucleic acid and peptide sequences, as well as related methods and compositions, including anti-cancer immunogenic agent(s) (e.g. vaccines and chimeric molecules) that elicit an immune response specifically directed against cancer cells expressing a CAIX antigenic marker. The novel CAIX variant and related compositions are useful in a wide variety of treatment modalities including, but not limited to protein vaccination, DNA vaccination, and adoptive immunotherapy.</p>
>> Read More

AMINO SPHINGOGLYCOLIPID ANALOGUES (Fri, 05 May 2017)
<p id="p-0001" num="0000">The invention relates to amino sphingoglycolipid analogues and peptide derivatives thereof, compositions comprising these compounds and methods of treating or preventing diseases or conditions using such compounds, especially diseases or conditions relating to cancer, infection, atopic disorders, autoimmune disease or diabetes.</p>
>> Read More

COMPOSITION FOR THE TREATMENT OF IGF-1R EXPRESSING CANCER (Fri, 05 May 2017)
The present invention relates to a method for the treatment of IGF-IR expressing cancers as well as to a compositions and a kit for said traitment. From one aspect, the invention reates to the combined use of a first antibody for the determination of the IGF-IR status of a cancer and a second antibody used as an ADC for the treatment of said cancer.
>> Read More

ANTI-NRG1 (HEREGULIN) ANTIBODIES AND USES THEREOF (Fri, 05 May 2017)
The disclosure relates to human anti-NRG1 neutralizing monoclonal antibodies that do not interfere with the NRG1 binding to the HER3 receptor and uses thereof. More particularly, an isolated human monoclonal antibody comprising a heavy and light chain variable regions with specific CDRs defined by their sequences is disclosed.
>> Read More

ISOTOPIC METHODS FOR MEASUREMENT OF TRYPTOPHAN AND METABOLITES THEREOF (Fri, 05 May 2017)
Tryptophan degradation is a key metabolic pathway controlling immune reactions and evidence suggests that during cancer progression generation of tryptophan metabolites may be fundamental for immune escape promoting the malignant phenotype of cancer cells in an autocrine fashion. The present invention relates to methods of measuring mass tag labelled tryptophan and metabolites thereof and methods using the labelled molecules for monitoring in a subject the effectiveness of a treatment and of disease recurrence after treatment, for stratifying patients and for diagnosing suppression of an immune response in a subject.
>> Read More

ANTIBODY CONJUGATES COMPRISING TOLL-LIKE RECEPTOR AGONIST (Fri, 05 May 2017)
Provided herein are antibody conjugates comprising toll-like receptor agonists and the use of such conjugates for the treatment of cancer. In some embodiments, the conjugates comprise anti-HER2 antibodies.
>> Read More

NOVEL PROCESS FOR PREPARING THIENOPYRIMIDINE COMPOUND AND INTERMEDIATES USED THEREIN (Fri, 05 May 2017)
The present invention relates to a novel method for preparing thienopyrimidine compound having an activity of selectively inhibiting tyrosine kinase, specifically the mutant epidermal growth factor receptor tyrosine kinase; and a novel intermediate used therein. According to the method of the present invention, the industrial mass-production of the compound of Formula 1, which is useful as a therapeutic agent for non-small cell lung cancer induced by the mutant epidermal growth factor receptor tyrosine kinase, can be implemented more conveniently and efficiently than the conventional technology.
>> Read More

PODOPHYLLOTOXIN DERIVATIVES AND THEIR USE (Fri, 05 May 2017)
Provided herein are relates to derivatives of podophyllotoxin, compositions thereof, and using them for treating various types of cancer in a subject and/or delaying or regressing various types of tumor growths in a subject.
>> Read More

HUMANIZED ANTI-DKK2 ANTIBODY AND USES THEREOF (Fri, 05 May 2017)
The present invention relates to the discovery that inhibition of Dickkopf2 (DKK2) increases CD8+ cytotoxic T lymphocyte (CTL) activity, attenuates tumor, and hence suppresses tumor formation. Thus, in various embodiments described herein, the methods of the invention relate to methods of treating cancer by administering to a patient an effective amount of a humanized anti-DKK2 antibody, methods for providing anti-tumor immunity in a subject, methods of stimulating a T cell mediated immune response to a cell population or a tissue and suppressing tumor in a subject. Additionally, the current invention includes methods of diagnosing a cancer or a predisposition of developing a cancer or a metastasis and methods for determining the use of immunotherapy treatment or cancer vaccine for treating cancer. Furthermore, the invention encompasses a pharmaceutical composition for treating cancer as well as a kit for carrying out the aforementioned methods.
>> Read More

COMPOSITIONS AND METHODS FOR TARGETING CANCER-SPECIFIC SEQUENCE VARIATIONS (Fri, 05 May 2017)
The present invention relates to compositions and methods for targeting cancer-specific DNA sequences, such as copy number amplifications and other types of cancer-specific sequence variations, such as cancer-specific polymorphisms, insertions, or deletions. The present invention provides hereto sequence-specific DNA targeting agents targeting a sequence within the amplified DNA region or a sequence otherwise specific for a cancer cell compared to a non- cancer cell. The invention further relates to methods for treating cancer, comprising administering such sequence-specific DNA targeting agents. The invention further relates to methods for preparing sequence-specific DNA targeting agent, as well as screening methods using the DNA targeting agents.
>> Read More

DENDERIMER COMPOSITIONS AND USE IN TREATMENT OF NECROTIZING ENTEROCOLITIS AND OTHER GASTROINTESTINAL DISORDERS (Fri, 05 May 2017)
A dendrimer formulation, such as a PAMAM dendrimer or a multiarm PEG polymeric formulation has been developed for oral administration to the gastrointestinal tract for treatment of inflammatory diseases associated with infection or cancer. In the preferred embodiment, the dendrimers are in the form of dendrimer nanoparticles comprising poly(amidoamine) (PAMAM) hydroxyl-terminated dendrimers covalently linked to at least one therapeutic, prophylactic or diagnostic agent for treatment of one or more symptoms of necrotizing enterocolitis.
>> Read More

METHODS FOR IDENTIFICATION, ASSESSMENT, PREVENTION, AND TREATMENT OF METABOLIC DISORDERS USING PM20D1 AND N-LIPIDATED AMINO ACIDS (Fri, 05 May 2017)
The present invention relates to methods for identifying, assessing, preventing, and treating metabolic disorders and modulating metabolic processes using PM20D1 and N- lipidated amino acids.
>> Read More

COMPOSITIONS AND METHODS FOR INHIBITING ARGINASE ACTIVITY (Fri, 05 May 2017)
The invention relates to a novel class of compounds that exhibit activity inhibitory activity toward arginase, and pharmaceutical compositions comprising the compounds of the invention. Also provided herein are methods of treating cancer with the arginase inhibitors of the invention.
>> Read More

AMORPHOUS SOLID FORM OF A BET PROTEIN INHIBITOR (Fri, 05 May 2017)
The present invention relates to an amorphous solid form of (4S)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one, and processes for its preparation, which is an inhibitor of BET proteins such as BRD2, BRD3, BRD4, and BRD-t and is useful in the treatment of various diseases such as cancer.
>> Read More

SSTR-TARGETED CONJUGATES AND PARTICLES AND FORMULATIONS THEREOF (Fri, 05 May 2017)
Conjugates of an active agent such as DM1 attached to a targeting moiety, such as a somatostatin receptor binding moiety, via a linker, and particles comprising such conjugates have been designed. Such conjugates and particles can provide improved temporospatial delivery of the active agent, improved biodistribution and penetration in tumor, and/or decreased toxicity. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer.
>> Read More

WEE 1 KINASE INHIBITORS AND METHODS OF MAKING AND USING THE SAME (Fri, 05 May 2017)
A compound, or a pharmaceutically acceptable salt thereof, having a chemical structure of formula (I) or formula (II), and methods of using these compounds to treat cancer in an individual.
>> Read More

NEW COMPOUND FOR INHIBITING BINDING BETWEEN DX2 PROTEIN AND P14/ARF PROTEIN, AND PHARMACEUTICAL COMPOSITION FOR TREATING OR PREVENTING CANCER DISEASE CONTAINING SAME AS EFFECTIVE INGREDIENT (Thu, 04 May 2017)
The present invention relates to a new compound for inhibiting binding between a DX2 protein and a p14/ARF protein, and a medical use thereof. A review of the in vitro and in vivo anticancer effect of the compound shows that the compound has an excellent anticancer effect and thus is useful as a drug for treating various cancer diseases including lung cancer, and has a more improved anticancer effect particularly by inhibiting resistance to an anticancer drug of Adriamycin in a cell line which is resistant to an anticancer drug such as Adriamycin, and thus can be used as an anticancer adjuvant for improving the anticancer effect. In addition, the present invention relates to a composition for diagnosing lung cancer comprising an AIMP2-DX2 protein or a fragment thereof, and is effective in diagnosis of lung cancer because whether or not a subject has lung cancer is confirmed only by using a serum sample of the subject.
>> Read More

Substituted pyrrolopyrimidines as HDM2 inhibitors (Wed, 03 May 2017)
<p id="p-0001" num="0000">The present invention provides substituted pyrrolopyrimidines of Formula I as described herein or a pharmaceutically acceptable salt or solvate thereof:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.10mm" wi="54.95mm" file="US09637493-20170502-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> The representative compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compositions comprising the above compounds and potential methods of treating cancer using the same. </p>
>> Read More

MODULATION OF NOVEL IMMUNE CHECKPOINT TARGETS (Fri, 28 Apr 2017)
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 as well as 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 Prdm1 and c-Maf cooperatively regulate the expression of the co-inhibitory receptor module. This critical molecular circuit underlies the co-expression of co-inhibitory receptors in dysfunctional T cells and identifies novel regulators of T cell dysfunction.
>> Read More

COMPOSITIONS AND METHODS OF REGULATING CANCER RELATED DISORDERS AND DISEASES (Fri, 28 Apr 2017)
Provided herein are naphthylic derivative compounds, or pharmaceutically acceptable salts thereof, that are useful for inhibiting cancers. Also provided herein are methods of using effective amounts of said compounds, optionally with pharmaceutical carriers, for the treatment of cancers within human subjects.
>> Read More

PYRIDONE DERIVATIVES AND THEIR USE AS KINASE INHIBITORS (Fri, 28 Apr 2017)
Disclosed in the present application is a compound of formula (I) as defined herein as well as a pharmaceutical composition comprising said compound. Further disclosed in the present application is the use of such pharmaceutical compositions for treating diseases, namely inter alia for use in the treatment of cancer, metabolic, inflammatory, autoimmune and viral diseases. The compounds disclosed herein are inhibitors of MNK1 and/or MNK2 kinases.
>> Read More

PRODRUGS OF 2-(4-(3-((4-AMINO-7-CYANO-IMIDAZO[2,1-F][1,2,4]TRIAZIN-2-YL)AMINO)PHENYL)PIPERAZ IN-1-YL)PROPANAMIDE DERIVATIVES AS CK2 INHIBITORS FOR THE TREATMENT OF CANCER (Fri, 28 Apr 2017)
PRODRUGS OF IMIDAZOTRIAZINE COMPOUNDS AS CK2 INHIBITORS The invention provides pharmaceutically active compounds of formula (I) and prodrugs thereof. The formula (I) 2-(aminophenylamino)-4- amino-7-cyano-imidazo[2,1-f][1,2,4]triazine derivatives inhibit CK2 protein kinase activity, thereby making them useful for treating cancer, psoriasis and rheumatoid arthritis.
>> Read More

COFACTOR ANALOGS AS METHYLTRANSFERASE INHIBITORS FOR TREATING CANCER (Fri, 28 Apr 2017)
Compounds having methyltransferase inhibitory activity are disclosed. The compounds have the structure (I) They are useful in the treatment of cancer and similar diseases associated with inappropriate methyltransferase activity.
>> Read More

PIPERAZINYL NORBENZOMORPHAN COMPOUNDS AND METHODS FOR USING THE SAME (Fri, 28 Apr 2017)
Disclosed herein, inter alia, are piperazinyl norbenzom orphan compounds and uses thereof, including, for example, methods for treating a CNS disease, treating traumatic brain injury, improving cognition, or diagnosing and treating cancer.
>> Read More

BENZOLACTAM COMPOUNDS AS PROTEIN KINASE INHIBITORS (Fri, 28 Apr 2017)
The invention provides a compound of formula (0): or a pharmaceutically acceptable salt, N-oxide or tautomer thereof. The compounds are inhibitors of ERK 1/2 kinases and will be useful in the treatment of ERKl/2-mediated conditions. The compounds are therefore useful in therapy, in particular in the treatment of cancer.
>> Read More

PHENYL INDOLE ALLOSTERIC INHIBITORS OF P97 ATPASE (Fri, 28 Apr 2017)
The present invention is directed to methods of inhibiting p97 and compounds and compositions useful in such methods. Diseases and conditions the can be treated with the compounds and compositions of the invention include, but are not limited to, cancer and neurodegenerative disorders susceptible to treatment by inhibition of p97.
>> Read More

2-BETA-NAPHTHYL-ACETIC ACID ANALOGS AS AKR1C3 INHIBITORS AND METHODS OF USING SAME (Fri, 28 Apr 2017)
The invention includes 2-β-naphthyl-acetic acid derivatives, which are selective AKR1C3 inhibitors. In certain embodiments, the compounds of the invention are R-naproxen analogs. The invention further includes methods of treating cancer, such as prostate cancer and/or castration-resistant prostate cancer, using at least one compound of the invention.
>> Read More

PSMA TARGETED RADIOHALOGENATED UREAS FOR CANCER RADIOTHERAPY (Fri, 28 Apr 2017)
PPSMA binding scaffolds with radioiodinated, radiobrominated and radioastatinated labeled prosthetic groups are disclosed. Pharmaceutical compositions and methods of treating PSMA expressing cells or tumors also are disclosed.
>> Read More

LAPACHONE DERIVATIVES CONTAINING TWO REDOX CENTERS AND METHODS OF USE THEREOF (Fri, 28 Apr 2017)
Provided herein are compounds containing two redox centers including a chalcogen redox center of the formula: wherein: R1, R2, X1, X2, Y1, and m are as defined herein. Also provided herein are pharmaceutical composition of the present compounds and methods of treatment using the compounds including their use in the treatment of cancer.
>> Read More

METHODS FOR DIAGNOSING PANCREATIC CANCER (Thu, 27 Apr 2017)
The present disclosure relates to the use of one or more biomarkers to determine the presence of pancreatic cancer precursor lesions or pancreatic cancer in a subject. This disclosure is based, at least in part, on the discovery that early to invasive stages of pancreatic cancer release or secrete biomarkers that can be detected in biological samples of a subject. Accordingly, in certain non-limiting embodiments, the present disclosure provides for methods and kits for determining the presence of one or more biomarkers in a biological sample of a subject, and methods of using such determinations in selecting a therapeutic regimen for a cancer subject and in methods of treating cancer subjects.
>> Read More

SUBSTITUTED BENZOAZEPINES AS TOLL-LIKE RECEPTOR MODULATORS (Thu, 27 Apr 2017)
Provided are compositions and methods useful for modulation of signaling through the Toll-like receptors TLR7 and/or TLR8. The compositions and methods have use in treating or preventing disease, including cancer, autoimmune disease, infectious disease, inflammatory disorder, graft rejection, and graft-verses-host disease.
>> Read More

PYRIMIDINE-2,4-DIAMINE DERIVATIVE AND ANTICANCER PHARMACEUTICAL COMPOSITION COMPRISING SAME AS EFFECTIVE INGREDIENT (Thu, 27 Apr 2017)
The present invention relates to a pyrimidine-2,4-diamine derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition for prevention or treatment of cancer comprising the same as an effective ingredient. A compound according to the present invention has the good effect of inhibiting anaplastic lymphoma kinase (ALK) activity, whereby a therapeutic effect on cancer cells having an anaplastic lymphoma kinase (ALK) fusion protein such as EML4-ALK, NPM-ALK, etc. can be enhanced and it is expected that a recurrence of cancer will be effectively inhibited. As such, the compound can be effectively used in a pharmaceutical composition for prevention or treatment of cancer.
>> Read More

METHODS OF TREATMENT USING ANTI-ERBB ANTIBODY MAYTANSINOID CONJUGATES (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">The application concerns methods of treatment using anti-ErbB receptor antibody-maytansinoid conjugates, and articles of manufacture suitable for use in such methods. In particular, the invention concerns ErbB receptor-directed cancer therapies, using anti-ErbB receptor antibody-maytansinoid conjugates.</p>
>> Read More

COMPOUNDS USEFUL AS IMMUNOMODULATORS (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">The present disclosure generally relates to compounds useful as immunomodulators. Provided herein are compounds, compositions comprising such compounds, and methods of their use. The disclosure further pertains to pharmaceutical compositions comprising at least one compound according to the disclosure that are useful for the treatment of various diseases, including cancer and infectious diseases.</p>
>> Read More

GEMCITABINE PRODRUGS AND USES THEREOF (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">The present invention provides compounds according to formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="40.89mm" wi="53.76mm" file="US20170107245A1-20170420-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and pharmaceutically acceptable salts thereof. For compounds of formula I, R<sup>1 </sup>and R<sup>2 </sup>are independently selected from the group consisting of H, —C(═O)—(CH<sub>2</sub>)<sub>2</sub>-aryl, and —C(═O)—(CH<sub>2</sub>)<sub>n</sub>—C(═O)—NH-aryl. The subscript n is from 2 to 6. R<sup>3 </sup>is selected from the group consisting of H and —C(═O)—O—R<sup>4</sup>; and R<sup>4 </sup>is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, arylalkyl, substituted arylalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl and substituted heteroalkyl. Compounds are provided wherein at least one of R<sup>1 </sup>and R<sup>2 </sup>is other than H. Pharmaceutical compositions, methods for inhibiting the growth of cancer cells, and methods for the treatment of cancer are also provided.</p>
>> Read More

NEW COMPOUNDS (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">The invention relates to new naphthyridine 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

MACROCYCLIC COMPOUNDS AS TRK KINASE INHIBITORS (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">Compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, D, R<sup>2</sup>, R<sup>2a </sup>R<sup>3 </sup>and R<sup>3a </sup>are as defined herein, are inhibitors of Trk kinases and are useful in the treatment of pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.54mm" wi="56.30mm" file="US20170107232A1-20170420-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

DETECTING MUTATIONS AND PLOIDY IN CHROMOSOMAL SEGMENTS (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.</p>
>> Read More

METHODS FOR STABILIZING HYPOXIA INDUCIBLE FACTOR-2 ALPHA AS A METHOD FOR TREATING CANCER (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">Disclosed herein is {[5-(3-fluorophenyl)-3-hydroxypyridine-2-carbonyl]-amino} acetic acid and the ester and amide prodrugs thereof, that can stabilize hypoxia inducible factor-2 alpha (HIF-2α) and thereby provide a method for treating cancer. Further disclosed are compositions which comprise {[5-(3-fluorophenyl)-3-hydroxypyridine-2-carbonyl]-amino} acetic acid and/or a prodrug thereof which can be used to treat cancer.</p>
>> Read More

THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">Provided are compounds useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a compound described herein.</p>
>> Read More

INHIBITORS OF LATE SV40 FACTOR (LSF) AS CANCER CHEMOTHERAPEUTICS (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">The present invention is directed to methods, compositions and kits for treatment of cancer, e.g. heptacellular carcinoma. In some embodiments, the present invention discloses the use of a small-molecule compound of formula (I)-(XXVI) and (III′) as disclosed herein to inhibit transcription factor Late SV40 Factor (LSF) for treatment of cancer, e.g., HCC.</p>
>> Read More

PYRIDYL PIPERIDINES (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">The invention provides novel substituted pyridyl piperidine compounds according to Formula (I) which are Wnt pathway inhibitors, their manufacture and use for the treatment of hyperproliferative diseases such as cancer, inflammatory or degenerative diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.35mm" wi="69.85mm" file="US20170107222A1-20170420-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

PEPTIDOMIMETIC MACROCYCLES AS MODULATORS OF MCL-1 (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">The disclosed peptidomimetic macrocycles modulate the activity of MCL-1. Myeloid cell leukemia 1 (MCL-1) is a protein that inhibits cell death. Peptidomimetic macrocycles, pharmaceutical compositions, and methods disclosed herein can be used for the treatment of disease in which MCL-1 is over-expressed, such as cancer. In particular, MCL-1-modulating peptidomimetic macrocycles disclosed herein can be applied in the setting of resistance to BCL-2 family inhibitors, which is often engendered by MCL-1 over-expression or hyper-activation.</p>
>> Read More

PROCESS METHODS FOR PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">A process for the synthesis of quinazolinone containing compounds which may be useful for the treatment of cancer, is hereby disclosed. In addition, compound intermediates relating to these processes are also disclosed.</p>
>> Read More

TRKA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">The present invention is directed to a bicyclic heteroaryl benzamide compounds of formula (I) which are tropomyosin-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> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="55.29mm" file="US20170107204A1-20170420-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

Small Molecule Transcription Modulators of Bromodomains (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">This disclosure relates generally to compounds and compositions comprising one or more indole analogs. These compounds are useful for treating diseases associated with NF-kB and p53 activity, such as cancer and inflammatory diseases.</p>
>> Read More

MULTI-MODAL BIOPROBE FOR BLADDER CANCER IMAGING AND PHOTODYNAMIC THERAPY (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">The present invention relates to 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, the present invention provides a multi-modal lanthanide-porphyrin PDT agent (Er—R<sub>3</sub>) that are capable of killing the bladder tumor cells selectivity via <sup>1</sup>O<sub>2 </sub>from porphyrin moiety and affording the fluorescence imaging simultaneously upon Er—R<sub>3 </sub>binding with the integrin α<sub>v</sub>β<sub>3 </sub>isoform in bladder cancer cells.</p>
>> Read More

METHOD FOR CONTROLLING CANCER METASTASIS OR CANCER CELL MIGRATION BY MODULATING THE CELLULAR LEVEL OF LYSYL TRNA SYNTHETASE (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">The present invention relates to a novel function of lysyl tRNA synthetase, that is, lysyl tRNA synthetase interacts with 67LR through translocation of KRS into plasma membrane, and so enhances tumor (or cancer) cell migration, thereby having an effect on cancer metastasis. More specifically, it relates to method for controlling cancer metastasis or cancer cell migration by modulating an cellular level of lysyl tRNA synthetase, an use of an expression vector comprising a construct inhibiting KRS expression for preventing or treating cancer, an use of an agent inhibiting KRS activity for preventing or treating cancer, a method for screening an agent which modulates cancer metastasis or cancer cell migration, a method for screening an agent inhibiting an interaction between KRS and 67LR. Accordingly, cancer metastasis and cancer cell migration may be controlled using the inventive KRS, further the cellular metabolism related to laminin receptor (67LR) of plasma membrane may be controlled. The relationship between KRS and laminin receptor disclosed in the present invention may be very useful for treatment, prevention and/or diagnosis of various disease related to thereof.</p>
>> Read More

PYRIDYL BENZOTHIOPHENES AS KINASE INHIBITORS (Fri, 21 Apr 2017)
<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

Aptamer Conjugates With N-Heterocyclic Carbene Metal Complexes for Targeted Drug Delivery (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">An aptamer-N-heterocyclic-carbene metal complex conjugate (aptamer-NHCM conjugate) or an aptamer-bis-N-heterocyclic-carbene metal complex conjugate (aptamer-bis-NHCM conjugate) includes an aptamer coupled through a hydrolytically stable bond to an N-heterocyclic-carbene metal complex (NHCM) or a bis-N-heterocyclic-carbene metal complex (bis-NHCM). The aptamer-NHCM conjugate is prepared where the chosen aptamer displays selective binding to a cell specific receptor, such that the cytotoxic NHCM can be directed specifically to cells responsible for a target disease (e.g., a specific cancer type). A method of preparing the aptamer-N-heterocyclic-carbene metal complex conjugate involves installing a coupling group to an N-heterocyclic-carbene metal complex that can specifically bond with a functional group on an aptamer; the bond, covalent or non-covalent, is stable hydrolytically in the absence of an environment that promotes intentional cleavage of the bond.</p>
>> Read More

SUBSTITUTED NITROGEN-CONTAINING HETEROCYCLIC DERIVATIVES, PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME AND APPLICATIONS OFANTITUMOR THEREOF (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">Disclosed are new substituted nitrogen-containing heterocyclic derivatives represented by formula (I) as AKT inhibitors, optical isomers, pharmaceutically acceptable salts or solvates thereof, wherein the definition of R1, R2, R3, R4, R5, R6, ring A, ring C, B, Q, Y, Z and m is shown in the description for details. In addition, medicaments comprising the derivatives as active components are also disclosed, which can be useful for treating proliferative diseases, such as cancer and inflammation, especially diseases relating to AKT kinase.</p>
>> Read More

PROTEASOME INHIBITORS AND USES THEREOF (Fri, 21 Apr 2017)
The compounds of the present invention are represented by the following compounds having Formula (I) where the substituents R, R1 -R5, k, m, n, and q are as defined herein. These compounds are used in the treatment of cancer, immunologic disorders, autoimmune disorders, neurodegenerative disorders, or inflammatory disorders, infectious disease, or for providing immunosuppression for transplanted organs or tissues.
>> Read More

FLUORESCENT ANTICANCER PLATINUM DRUGS (Fri, 21 Apr 2017)
The present disclosure is in relation to the field of nanotechnology and cancer therapeutics. In particular, the present disclosure relates to fluorescent platinum based compounds. The disclosure further relates to synthesis of said fluorescent platinum based compounds, nanoparticles and compositions comprising said fluorescent platinum based compounds/nanoparticles. The disclosure also relates to methods of managing cancer by the fluorescence changes between aforesaid platinum based compounds and corresponding free ligands, nanoparticles and compositions.
>> Read More

CD73 BLOCKING AGENTS (Fri, 21 Apr 2017)
Provided are antibodies that bind and inhibit CD73, are capable of increasing the proliferation of T cells in the presence of CD39- expressing B cells and ATP. The disclosure 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 cancer.
>> Read More

DRUG-LINKER CONJUGATE PHARMACEUTICAL COMPOSITIONS (Fri, 21 Apr 2017)
Compositions are disclosed having a cytotoxic and/or vascular disrupting agent (VDA) payload attached to a linker. The linker can be a cathepsin B protease cleavable linker or a non-cleavable linker that may degrade intracellularly. Methods for making and using the compositions are also provided. The compositions can be provided to a patient in need thereof with the composition coming into contact with a cancer cell to activate or release the cytotoxic and/or vascular disrupting agent payload.
>> Read More

COMPOUNDS (Fri, 21 Apr 2017)
Anti-angiogenic treatments, for example treatment of ocular neovascularization or cancer, treatments of hyperpermeability disorders, treatments of neuropathic and neurodegenerative disorders, pain treatments, methods of treating or preventing fibrosis and compounds for use in such methods are described.
>> Read More

CONFORMATIONALLY CONSTRAINED MACROCYCLIC COMPOUNDS AS PIN1 MODULATORS (Fri, 21 Apr 2017)
Conformationally constrained macrocyclic compounds of formula (I), including substituents E, G, and Q, as defined in the description and the claims, and salts thereof, have the property to modulate the activity of the peptidyl-prolyl cis/trans isomerases Pin1. Thus, these compounds and pharmaceutical compositions containing said compounds may be useful in the treatment and/or prevention of diseases or conditions in the area of proliferative disorders and diseases, such as e.g. cancer, inflammatory diseases, transplant rejection, viral infections, osteolytic bone diseases, cardiac diseases, cardiovascular diseases, respiratory diseases, acute neurological diseases, neurodegenerative diseases, immune disorders, and lymphoproliferative theileriosis.
>> Read More

CONFORMATIONALLY CONSTRAINED MACROCYCLIC COMPOUNDS (Fri, 21 Apr 2017)
Conformationally constrained macrocyclic compounds of formula (I), including substituents E with at least one ester moiety, G and Q, as defined in the description and the claims, and salts thereof, can be metabolized to compounds that have the property to modulate the activity of the peptidyl-prolyl cis/trans isomerase Pin1. In addition, they show antiproliferative activity on various cancer cell lines. Thus, these compounds and pharmaceutical compositions containing said compounds may be useful in the treatment and/or prevention of diseases or conditions in the area of proliferative disorders and diseases, such as e.g. cancer, inflammatory diseases, transplant rejection, viral infections, osteolytic bone diseases, cardiac diseases, cardiovascular diseases, respiratory diseases, acute neurological diseases, neurodegenerative diseases, immune disorders, and lymphoproliferative theileriosis.
>> Read More

COMPOUNDS, COMPOSITIONS AND METHODS OF USE AGAINST STRESS GRANULES (Fri, 21 Apr 2017)
Herein, compounds, compositions and methods for modulating inclusion formation and stress granules in cells related to the onset of neurodegenerative diseases, musculoskeletal diseases, cancer, ophthalmological diseases, and viral infections are described.
>> Read More

BRD4-KINASE INHIBITORS AS CANCER THERAPEUTICS (Fri, 21 Apr 2017)
Disclosed herein are compounds that are inhibitors of BDR4 and their use in the treatment of cancer. Methods of screening for selective inhibitors of BDR4 are also disclosed. In certain aspects, disclosed are compounds of Formula I through IV.
>> Read More

EP4 ANTAGONISTS (Fri, 21 Apr 2017)
We provide compounds given by Formula I, which is shown in FIG. 3, or pharmaceutically acceptable salts thereof, as well as formulations thereof and methods of use of those compounds and formulations for treatment of cancer.
>> Read More

CONFORMATIONALLY CONSTRAINED MACROCYCLIC COMPOUNDS AS PIN1 MODULATORS (Fri, 21 Apr 2017)
Conformationally constrained macrocyclic compounds of formula (I), including substituents E, G, and Q, as defined in the description and the claims, and salts thereof, have the property to modulate the activity of the peptidyl-prolyl cis/trans isomerases Pin1. Thus, these compounds and pharmaceutical compositions containing said compounds may be useful in the treatment and/or prevention of diseases or conditions in the area of proliferative disorders and diseases, such as e.g. cancer, inflammatory diseases, transplant rejection, viral infections, osteolytic bone diseases, cardiac diseases, cardiovascular diseases, respiratory diseases, acute neurological diseases, neurodegenerative diseases, immune disorders, and lymphoproliferative theileriosis.
>> Read More

COMPOUNDS USEFUL AS IMMUNOMODULATORS (Fri, 21 Apr 2017)
The present disclosure generally relates to compounds useful as immunomodulators. Provided herein are compounds, compositions comprising such compounds, and methods of their use. The disclosure further pertains to pharmaceutical compositions comprising at least one compound according to the disclosure that are useful for the treatment of various diseases, including cancer and infectious diseases. The compounds have formula (I), wherein R2 is selected from (II) and (III).
>> Read More

CONFORMATIONALLY CONSTRAINED MACROCYCLIC COMPOUNDS (Fri, 21 Apr 2017)
Formula (I); Conformationally constrained macrocyclic compounds of formula (I), including substituents E with at least one ester moiety, G and Q, as defined in the description and the claims, and salts thereof, can be metabolized to compounds that have the property to modulate the activity of the peptidyl-prolyl cis/trans isomerase Pin1. In addition, they show antiproliferative activity on various cancer cell lines. Thus, these compounds and pharmaceutical compositions containing said compounds may be useful in the treatment and/or prevention of diseases or conditions in the area of proliferative disorders and diseases, such as e.g. cancer, inflammatory diseases, transplant rejection, viral infections, osteolytic bone diseases, cardiac diseases, cardiovascular diseases, respiratory diseases, acute neurological diseases, neurodegenerative diseases, immune disorders, and lymphoproliferative theileriosis.
>> Read More

ANTI-TUMOR PHARMACEUTICAL APPLICATION OF PENTACYCLIC TRITERPENE SAPONIN COMPOUNDS OF SZECHUAN MELANDIUM ROOT (Thu, 20 Apr 2017)
The invention provides compounds of structural formula I or a salt thereof, and total saponins comprising such compounds in the preparation of anti-tumor agents. The present study of this invention showed that the compounds of formula I and the related total saponins had strong inhibitory effects on the proliferation of several human tumor cell lines, such as hepatocarcinoma, gastric cancer, colon cancer, breast cancer and melanoma cell lines, also the combination of structural formula I and the chemical agents could fairly well reduce toxicity and increase treatment effects.
>> Read More

BINDING INHIBITOR BETWEEN TCTP DIMER TYPE IGE-DEPENDENT HISTAMINE RELEASING FACTOR AND RECEPTOR THEREOF, AND USE THEREOF (Thu, 20 Apr 2017)
The present invention relates to a receptor-binding domain of an IgE-dependent histamine releasing factor (HRF), and a use thereof and, more specifically, ascertains, as an HRF framework region, an FL domain and an H2 domain which bind to a receptor of an HRF existing in a cell membrane, ascertains the C-terminus of the HRF, and ascertains that a material binding thereto inhibits IL-8 secretion, thereby determining that the FL and H2 domains and the C-terminus can be utilized in: the development of a therapeutic agent for and prevention of HRF-related diseases including malaria and inflammatory diseases such as asthma, bronchitis, chronic obstructive pulmonary disease, bronchiectasis, rhinitis, atopic dermatitis, hives, hay fever, conjunctivitis, anaphylactic allergic diseases, pneumonia, arthritis, nephritis, psoriasis, dermatitis, Crohn's disease, enteritis, gingivitis, arteriosclerosis, coronary arteritis, hepatitis, Behcet's disease, bladder cancer, prostatitis, pyelonephritis, glomerulonephritis, osteomyelitis, thyroiditis, uveitis, abdominal cavity inflammation, meningitis, pulmonary fibrosis and rheumatoid arthritis; and a method for screening for the HRF-related diseases.
>> Read More

DIHYDROOXADIAZINE COMPOUNDS FOR TREATING INFECTIONS AND CANCER (Thu, 20 Apr 2017)
The invention relates to oxadiazine compounds and their use in medicine, particularly in treating and /or preventing infections caused by a bacterium, fungus or virus or in treating and/or preventing cancer. Additionally, the invention relates to a process for obtaining the compounds of the invention, said process comprising the steps of cultivating a strain of Dolichospermum sp in an aqueous nutrient medium with assimilable carbon and nitrogen sources and salts, under controlled aerobic conditions, and then recovering the compound of general formula (I) from the culture broth.
>> Read More

Compounds and their uses (Thu, 20 Apr 2017)
A compound of formula (A) or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, prodrug, codrug, cocrystal, tautomer, racemate, stereoisomer or mixture thereof: wherein X is nitro or hydrogen; Y is hydrogen or a side group. Preferably, Y is selected from H, amino, amide, ester, carboxy and its esters and amides, alkyl, alkenyl, alkynyl, cycloalkyl, alkaryl, aryl, heterocyclic or heteroaryl groups, all of which may be optionally substituted with heteroatoms and/or side groups, and wherein any chains may be straight or branched. More preferably, Y is optionally substituted imidazolyl, optionally substituted pyrazolyl, optionally substituted triazolyl or tetrazolyl. More preferably, Y is phenyl or substituted phenyl. The compounds of formula (A) are inhibitors of S100P/RAGE and are useful in the treatment of cancer, in particular pancreatic cancer.
>> Read More

Synergistic pharmaceutical composition useful for the treatment of lung cancer (Wed, 19 Apr 2017)
<p id="p-0001" num="0000">The present invention relates to a synergistic pharmaceutical composition comprising Compound C2 (Neo-isopulegol), C3 (Iso-pulegol) and C4 (Citronellol) derived from herbal seed extract of <i>Litsea cubeba </i>useful for the treatment of lung cancer. The present invention also relates to the activity of compounds C2 or C3 or C4 either alone or in combination in killing of A549 lung cancer cells.</p>
>> Read More

COMPOUNDS FOR TREATMENT OF CANCER AND EPIGENETICS (Fri, 14 Apr 2017)
Compounds For Inhibition Of Cancer and Epigenesis The present invention relates to quinolines and 5,6,7,8-tetrahydroacridines of the formula (I) wherein Z1, Z2, X, R1 to R8 and Y are defined as described in the specification, or a pharmaceutically acceptable form or prodrug thereof, that are inhibitors of methyl transferases such as protein lysine methyltransferases and more particularly SMYD3. The present invention also relates to the methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of disorders/conditions/diseases involving, relating to or associated with enzymes having methyl transferase activities/functions and/or via unspecified/multi-targeted mechanisms.
>> Read More

TRIGGER-ACTIVATABLE METABOLIC SUGAR PRECURSORS FOR CANCER-SELECTIVE LABELING AND TARGETING (Fri, 14 Apr 2017)
Disclosed are compounds for the selective labeling of cell-surface sugars in cancer cells. The compounds are activatable by triggers specific to cancer cells, and, when metabolized, label a cancer cell surface sugar with an azide chemical group. Facilitated by a click chemistry reaction, combination of the cell surface-expressed azide with a alkynyl- drug conjugate enables efficient targeted drug delivery to cancer cells with reduced toxicity Also disclosed are compounds for delivering a drug to an azide-bearing cancer cell, and methods of treating cancer using the compounds of the invention.
>> Read More

ANTI-LAG3 ANTIBODIES AND USES THEREOF (Fri, 14 Apr 2017)
The present invention provides antibodies that bind to the T cell co-inhibitor lymphocyte activation gene 3 (LAG3) protein, and methods of use. In various embodiments of the invention, the antibodies are fully human antibodies that specifically bind to LAG3. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing LAG3 activity, thus providing a means of treating a disease or disorder such as cancer or viral infection.
>> Read More

PROTECTED FUMARIC ACID-BASED METABOLITES FOR THE TREATMENT OF AUTOIMMUNE DISEASES (Fri, 14 Apr 2017)
The present invention provides novel cell-permeable fumarate acyl mercaptoethylamines (FAMs) which have cellular effects including induction of Nrf2 and inhibition of the NFkB pathway. These compounds have utility in medicine including their use in treatment of diseases such as Multiple sclerosis, Non-alcoholic Steatohepatitis, Psoriasis, Inflammatory Arthritis, Inflammatory Bowel Disease, Asthma, Chronic Obstructive Pulmonary Disease, Cancer, Parkinson's Disease, Alzheimer's Disease, Huntington's Disease and Amyotrophic Lateral Sclerosis.
>> Read More

COMBINATION THERAPY (Fri, 14 Apr 2017)
This invention relates toa combination of gemcitabine-[phenyl-benzoxy-L-alaninyl)]- phosphate (chemical name: 2'-Deoxy-2',2'-difluoro-D-cytidine-5'-O-[phenyl (benzoxy-L- alaninyl)] phosphate)(NUC-1031) and a platinum-based anticancer agentselected from carboplatin, dicycloplatin, oxaliplatin, satraplatin and nedaplatin. The combinations are useful in the treatment of cancer and particularly ovarian cancer.
>> Read More

COMPOUNDS AND THERAPEUTIC USES THEREOF (Fri, 14 Apr 2017)
The invention relates to novel compounds with the ability to link an immune response to a defined therapeutic target, to the use of said compounds in treating cancer, to compositions containing said compounds, processes for their preparation and to novel intermediates used in said process.
>> Read More

COMPOUNDS AND THERAPEUTIC USES THEREOF (Fri, 14 Apr 2017)
The invention relates to novel compounds with the ability to link an immune response to a defined therapeutic target, to the use of said compounds in treating cancer and a disease or disorder mediated and/or caused by an infective agent, to compositions containing said compounds, processes for their preparation and to novel intermediates used in said process.
>> Read More

PTEFB-INHIBITOR-ADC (Fri, 14 Apr 2017)
It is an object of the present invention to provide substances which, after administration at a relatively low concentration, unfold apoptotic action and may therefore be of benefit for cancer therapy. To achieve this object, the invention provides conjugates of a binder or derivatives thereof with one or more active compound molecules, the active compound molecule being a CDK9 inhibitor attached to the binder via a linker L. The binder is preferably a binder protein or peptide, particularly preferably a human, humanized or chimeric monoclonal antibody or an antigen-binding fragment thereof, in particular an anti-TWEAKR antibody or an antigen-binding fragment thereof or an anti-EGFR antibody or an antigen-binding fragment thereof. Particular preference is given to an anti-TWEAKR antibody which binds specifically to amino acid D in position 47 (D47) of TWEAKR (SEQ ID NO: 169), in particular the anti-TWEAKR antibody TPP-2090, or the anti-EGFR antibodies cetuximab, TPP-4030, TPP-5653, or nimotuzumab. The inventors have found a number of ways to attach the binder to the CDK9 inhibitor in order to achieve the object mentioned above.
>> Read More

INHIBITORS OF MENAQUINONE BIOSYNTHESIS (Fri, 07 Apr 2017)
Provided herein are compounds of Formula (I) and pharmaceuticals acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, and prodrugs thereof. Also provided are pharmaceutical compositions, kits, and methods involving the inventive compounds for the treatment of an infectious disease (e.g., bacterial infection (e.g., tuberculosis, methicillin- resistant Staphylococcus aureus).
>> Read More

ANTHRANILYL-ADENOSINEMONOSULFAMATE ANALOGS AND USES THEREOF (Fri, 07 Apr 2017)
Provided herein are compounds of Formula (I) and pharmaceuticals acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, and prodrugs thereof. Also provided are pharmaceutical compositions, kits, and methods involving the inventive compounds for the treatment and/or of an infectious disease (e.g., bacterial infection (e.g., P. aeruginosa infection).
>> Read More

18F-TAGGED INHIBITORS OF PROSTATE SPECIFIC MEMBRANE ANTIGEN (PSMA) AND THEIR USE AS IMAGING AGENTS FOR PROSTATE CANCER (Fri, 07 Apr 2017)
The present invention generally relates to the field of radiopharmaceuticals and their use in nuclear medicine as tracers and imaging agents for various disease states of prostate cancer.
>> Read More

NEW IMIDAZO[4,5-B]PYRIDINE DERIVATIVES AS DUAL DYRK1/CLK1 INHIBITORS (Fri, 07 Apr 2017)
(Formula I) Compounds of formula (I) usefull for the treatment of cancer, neurodegenerative disorders and metabolic disorders.
>> Read More

NEW PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES AS DUAL DYRK1/CLK1 INHIBITORS (Fri, 07 Apr 2017)
(Formula I) Compounds of formula (I) usefull for the treatment of cancer, neurodegenerative disorders and metabolic disorders.
>> Read More

ANTI-PD-1 ANTIBODIES AND COMPOSITIONS (Fri, 07 Apr 2017)
This invention relates to anti-PD-1 antibodies and methods of using them in treating diseases and conditions related to PD-1activity, e.g., cancer.
>> Read More

TRILOBINE AND ITS NATURAL ANALOGS FOR USE AS A DRUG (Fri, 07 Apr 2017)
Trilobine and its natural triple-bridged bisbenzylisoquinoline alkaloidal analogues as DNMT inhibitors for use as a drug for the treatment of cancer and neurological diseases and for cell reprogramming, in particular to prime for chemotherapy or immunotherapy.
>> Read More

HEMI-SYNTHETIC TRILOBINE ANALOGS FOR USE AS A DRUG (Fri, 07 Apr 2017)
The invention concerns a compound of the following formula (I) or a pharmaceutically acceptable salt or solvate thereof as well as a pharmaceutical composition containing such a compound, and the use of such a compound as a drug, notably as a DNMT inhibitor, in particular in the treatment of cancer.
>> Read More

ISOINDOLINONE INHIBITORS OF THE MDM2-P53 INTERACTION HAVING ANTICANCER ACTIVITY (Fri, 07 Apr 2017)
The invention provides a compound of formula (I): (I) or tautomer or a solvate or a pharmaceutically acceptable salt thereof, wherein the various substituents are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds.
>> Read More

ISOINDOLINONE INHIBITORS OF THE MDM2-P53 INTERACTION HAVING ANTICANCER ACTIVITY (Fri, 07 Apr 2017)
The invention provides a compound of formula (I): (I) or tautomer or a solvate or a pharmaceutically acceptable salt thereof, wherein the various substituents are as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds.
>> Read More

CYTOTOXIC AND ANTI-MITOTIC COMPOUNDS, AND METHODS OF USING THE SAME (Fri, 07 Apr 2017)
Compounds of general formula (I) having cytotoxic and/or anti-mitotic activity and methods of using such compounds, as well as pharmaceutical compositions comprising such compounds. The compounds may also be conjugated with a targeting moiety, such as an antibody. Such conjugate compositions may be used in the treatment of cancer and other diseases. (I)
>> Read More

INHIBITORS OF KRAS G12C MUTANT PROTEINS (Fri, 07 Apr 2017)
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): (I) or a pharmaceutically acceptable salt, tautomer, stereoisomer or prodrug thereof, wherein Z, Y R3a, R3b, R4a, R4b, G1, G2, G3, G4, L1, m1, m2, m3, m4, n 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

THIOSEMICARBAZONES (Fri, 07 Apr 2017)
Described herein are thiosemicarbazone compounds and their use in therapy. More particularly, described herein a selection of dipyridyl thiosemicarbazone compounds, pharmaceutical compositions containing those compounds, and methods of treating cancer comprising administering those compounds and compositions.
>> Read More

INHIBITORS OF KRAS G12C MUTANT PROTEINS (Fri, 07 Apr 2017)
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 A, X, R3a, R3b, R4a, R4b, G1, G2, G3, G4, L1, L2, m1, m2, m3, m4, 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

INHIBITORS OF KRAS G12C MUTANT PROTEINS (Fri, 07 Apr 2017)
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): (I) or a pharmaceutically acceptable salt, tautomer, stereoisomer or prodrug thereof, wherein A, R3a, R3b, R4a, R4b, G1, G2, G3, G4, m1, m2, m3, m4, 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

INHIBITORS OF KRAS G12C MUTANT PROTEINS (Fri, 07 Apr 2017)
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 R1, R3a, R3b, R4a, R4b, G1, G2, G3, G4, m1, m2, m3, m4, 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

ANTI-CANCER COMPOUNDS AND CONJUGATES THEREOF (Fri, 07 Apr 2017)
Disclosed are compounds based on dolastatins, drug-conjugates, methods of preparing drug-conjugates, and uses thereof. Also disclosed are pharaceutical compositions and methods of treatment. The compounds and drug-conjugates disclosed herein can be used to treat diseases such as bladder cancer, breast cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, lung cancer, melanoma, non-Hodgkin lymphoma, glioblastoma, pancreatic cancer, prostate cancer, and thyroid cancer.
>> Read More

INHIBITORS OF KRAS G12C MUTANT PROTEINS (Fri, 07 Apr 2017)
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 A, R1, R3a, R3b, R4a, R4b, G2, G3, G4, m1, m2, m3, m4, 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

INHIBITORS OF KRAS G12C MUTANT PROTEINS (Fri, 07 Apr 2017)
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 A, B 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

COMPOSITIONS AND METHODS FOR TREATING CANCER (Fri, 07 Apr 2017)
Provided herein, inter alia, are compositions and methods useful for treating hvperproliferative diseases, including cancer and non-malignant hvperproliferative diseases.
>> Read More

AZOLYLACRYLOYL DERIVATIVES AS THERAPEUTIC AGENTS FOR SICKLE CELL DISEASE (Fri, 07 Apr 2017)
Azolylacryloyl derivatives with hypoxic properties are provided. The compounds have a generic formula: and are suitable for treating sickle cell disease and hypoxia-underlying diseases, e.g. hemorrhagic and traumatic shock, cardiac arrest and cardiogenic shock, traumatic brain injury, cancer, stroke, myocardial infarction, myocardial ischemia, vaso-occlusive crisis, etc.
>> Read More

METHODS OF REDUCING CHEMORESISTANCE AND TREATING CANCER (Fri, 07 Apr 2017)
Methods of treating cancer include administering a therapeutically effective amount of a pharmaceutical composition containing a pharmaceutically acceptable carrier and a compound that is a GPR55 antagonist to a subject having a tumor including cancer cells that have developed a resistance to one or more chemotherapeutic agents. In embodiments, the compound is a fenoterol analogue, such as for example, MNF.
>> Read More

QUINOLINE DERIVATIVE (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">A compound represented by general formula (I) has a strong Axl inhibitory activity by introducing a distinctive bicyclic structure in which a saturated carbon ring is fused to a pyridone ring, and can be a therapeutic agent for Axl-related diseases, for example, cancer such as acute myeloid leukemia, melanoma, breast cancer, pancreatic cancer, and glioma, kidney diseases, immune system diseases, and circulatory system diseases</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="51.48mm" wi="69.85mm" file="US20170088542A1-20170330-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

COMPOUNDS THAT INHIBIT MCL-1 PROTEIN (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I,</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.74mm" wi="68.58mm" file="US20170088560A1-20170330-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.</p>
>> Read More

BENZENETRICARBOXYLIC ACID AND METHODS OF USE (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">Methods of treating or preventing cancer and/or a neurodegenerative disorder in a subject are provided. The methods comprise administering to a subject a therapeutically effective amount of 1,2,3-benzenetricarboxylic acid or a hydrate or pharmaceutically acceptable salt thereof.</p>
>> Read More

COMPOSITIONS AND METHODS FOR DETECTING OR ELIMINATING SENESCENT CELLS TO DIAGNOSE OR TREAT DISEASE (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">Disclosed are agents (e.g., peptides, polypeptides, proteins, small molecules, antibodies, and antibody fragments that target senescent cells) and methods of their use for imaging senescent cells in vivo and for treating or preventing cancer, age-related disease, tobacco-related disease, or other diseases and disorders related to or caused by cellular senescence in a mammal. The methods include administering one or more of the agents of the invention to a mammal, e.g., a human. The agents, which specifically bind to senescent cells, can be labeled with a radioactive label or a therapeutic label, e.g., a cytotoxic agent.</p>
>> Read More

1-((3S,4R)-4-(3-FLUOROPHENYL)-1-(2-METHOXYETHYL)PYRROLIDIN-3-YL)-3-(4-METHYL-3-(2-METHYLPYRIMIDIN-5-YL)-1-PHENYL-1H-PYRAZOL-5-YL)UREA AS A TRKA KINASE INHIBITOR (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">Provided is Compound (I) or a pharmaceutically acceptable salt thereof, which is an inhibitor of TrkA kinase and is useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation and inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis, pelvic pain syndrome, diseases related to an imbalance of the regulation of bone remodeling, and diseases resulting from Connective Tissue Growth Factor aberrant signaling.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="48.43mm" wi="66.72mm" file="US20170087156A1-20170330-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

FURO[3,4-b]PYRAN COMPOUNDS AND PHARMACEUTICAL USES (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">Furo[3,4-b]pyran compounds similar in chemical structure to the natural product known as TAN-2483B and their use for treating cancer, osteoporosis, Type 2 diabetes, or immune diseases.</p>
>> Read More

BIOMARKERS FOR DETECTION OF BREAST CANCER IN WOMEN WITH DENSE BREASTS (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">Methods are provided for predicting and diagnosing the presence of breast cancer in women with dense breasts, as well as for assessing the therapeutic efficacy of a cancer treatment and determining whether a subject potentially is developing cancer.</p>
>> Read More

BENZIMIDAZOLE DERIVATIVES AND USES THEREOF (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">Benzimidazole derivatives of Formula I, that modulate the activity of ACSS2 are disclosed for therapeutic use. The fused imidazole ring of the compounds disclosed has a diarylmethyl or diarylmethanol moiety attached at the 2-position and the as compounds have at least one other substituent at the 5 or 6 position of the benzimidazole. Also disclosed are methods of using the benzimidazole compounds for the treatment of diseases or disorders, such as cancer.</p>
>> Read More

COMPOUNDS AND METHODS FOR INHIBITING JAK (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">Disclosed are compounds of formula (I), pharmaceutical compositions comprising such compounds and methods/uses of using the same, for example, for treating a JAK-related disorder, such as cancer, cancer cachexia or an immune disorder:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="61.81mm" wi="73.49mm" file="US20170088543A1-20170330-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">R<sup>1 </sup>is methyl or ethyl;</li> <li id="ul0002-0002" num="0000">R<sup>2 </sup>is selected from methyl, ethyl, methoxy and ethoxy;</li> <li id="ul0002-0003" num="0000">R<sup>3 </sup>is selected from hydrogen, chlorine, fluorine, bromine and methyl;</li> <li id="ul0002-0004" num="0000">R<sup>4 </sup>is selected from methyl, ethyl and —CH<sub>2</sub>OCH<sub>3</sub>;</li> <li id="ul0002-0005" num="0000">R<sup>5 </sup>and R<sup>6 </sup>are each individually methyl or hydrogen; and</li> <li id="ul0002-0006" num="0000">R<sup>7 </sup>is selected from methyl, ethyl, —(CH<sub>2</sub>)<sub>2</sub>OH and —(CH<sub>2</sub>)<sub>2</sub>OCH<sub>3</sub>, or a pharmaceutically acceptable salt thereof.</li> </ul> </li> </ul> </p>
>> Read More

CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">Chemical entities that are novel compounds, pharmaceutical compositions and methods of treatment of cancer are described.</p>
>> Read More

PHARMACEUTICAL COMPOSITIONS COMPRISING MONOTERPENES (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">The present invention provides a process for purifying a monoterpene or sesquiterpene having a purity greater than about 98.5% (w/w). The process comprises the steps of derivatizing the monoterpene (or sesquiterpene) to produce a monoterpene (or sesquiterpene) derivative, separating the monoterpene (or sesquiterpene) derivative, and releasing the monoterpene (or sesquiterpene) from the derivative. Also encompassed by the scope of the present invention is a pharmaceutical composition comprising a monoterpene (or sesquiterpene) having a purity greater than about 98.5% (w/w). The purified monoterpene can be used to treat a disease such as cancer. The present monoterpene (or sesquiterpene) may be administered alone, or may be co-administered with radiation or other therapeutic agents, such as chemotherapeutic agents.</p>
>> Read More

Fluorinated Derivatives of 3-Hydroxypyridin-4-Ones (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">Provided are compounds of Formula I which are derivatives of 3-Hydroxypyridin-4-ones. The compounds may be used in treatment of a medical condition related to a toxic concentration of iron. The compounds may be used for preparation of a medicament for treatment of a medical condition related to a toxic concentration of iron. The medical condition related to a toxic concentration of iron may be selected from the group consisting of: cancer, pulmonary disease, progressive kidney disease and Friedreich's ataxia.</p>
>> Read More

GEMCITABINE ANALOGS (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">Gemcitabine analogs, including monophosphorylated analogs, are described herein and are suitable for use in pharmaceutical compositions, kits and treatment methods. The treatment methods include treatment of viral infections, including, but not limited to, treatment of Hepatitis C Virus, and uncontrolled cellular proliferation, including cancer, such as, but not limited to, non-small cell lung cancer, pancreatic cancer, bladder cancer, breast cancer, liver cancer, esophageal cancer and lymphoma.</p>
>> Read More

INHIBITORS OF ALK AND SRPK AND METHODS OF USE (Fri, 31 Mar 2017)
The application relates to a compound of Formula (I): (I), which modulates the activity of ALK or SRPK, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which ALK or SRPK plays a role.
>> Read More

TEAD TRANSCRIPTION FACTOR AUTOPALMITOYLATION INHIBITORS (Fri, 31 Mar 2017)
The present disclosure compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the TEAD transcription factor, and are useful in the treatment of diseases related to the activity of TEAD transcription factor including, e.g., cancer and other diseases.
>> Read More

RNAi CONJUGATES, PARTICLES AND FORMULATIONS THEREOF (Fri, 31 Mar 2017)
Particles, including nanoparticles and microparticles, and pharmaceutical formulations thereof, comprising conjugates of an RNAi agent attached to a targeting moiety via a linker have been designed which can provide improved temporospatial delivery of the RNAi agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or infectious diseases.
>> Read More

HUMAN RPN2 DERIVED PEPTIDES USEFUL FOR TREATING CANCER (Fri, 31 Mar 2017)
The disclosure includes peptides derived from the C-terminus of proteasome PC repeat protein hRpn2/PSMD1, which binds to hRpn13 Pru domain with high affinity. Amino acids F948, Y950, and I951 were identified as necessary for the interaction of hRpn2 with hRpn13. These peptides are useful for treating diseases and disorders which are modulated by proteolysis via the ubiquitin-proteasome pathway. Such diseases and disorders include a viral infection, a neurodegenerative disorder, an inflammatory disorder, or cancer, especially hematological cancer, HPV associated cancer, ovarian cancer, prostate cancer, breast cancer, gastric cancer, or colorectal cancer. The disclosure includes methods of treating cancer in a patient comprising administering a peptide of the disclosure to the patient. The peptide may be the only chemotherapeutic administered to the patient or may be administered together with an additional chemotherapeutic agent.
>> Read More

DRUG FORMULATION BASED ON PARTICULATES COMPRISING POLYSACCHARIDE-VITAMIN CONJUGATE (Fri, 31 Mar 2017)
The present disclosure provides formulations for pharmacologically active reagents, including formulations based on particulates formed from a biodegradable polymer (e.g., a polysaccharide such as dextran) linked to a vitamin or related agent (e.g., folic acid). Hydrophobic pharmaceutically active agents (such as anti-cancer drugs, e.g., paclitaxel) are encapsulated into the polysaccharide-vitamin conjugate for the administration of paclitaxel. The active agent is in a core portion of the particulate, instead of on the surface of the particulate. Processes for making and using the particulates and compositions comprising the same are also disclosed. In particular, methods of cancer diagnosis and treatment are provided.
>> Read More

BIOMARKERS OF RESPONSE TO HIF-2-ALPHA INHIBITION IN CANCER AND METHODS FOR THE USE THEREOF (Fri, 31 Mar 2017)
Described herein are methods and systems for identifying and/or treating subjects having cancer who are more likely to respond to treatment with an inhibitor of the transcription factor HIF-2α.
>> Read More

BICYCLIC AND TRICYCLIC CAP BEARING MERCAPTOACETAMIDE DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS (Fri, 31 Mar 2017)
Histone deacetylases inhibitors (HDACIs) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a peripheral neuropathy, a neurological disease, traumatic brain injury, stroke, hypertension, malaria, an autoimmune disease, autism, autism spectrum disorders, and inflammation, also are disclosed.
>> Read More

MODIFIED CYTOTOXINS AND THEIR THERAPEUTIC USE (Fri, 31 Mar 2017)
The present disclosure generally provides compounds useful for treating cancer. In some aspects, the disclosure provides small-molecule cytotoxins that are chemically modified to include one or more moieties that include hydrophobic portions. In some embodiments, the disclosure provides small-molecule cytotoxins that are chemically modified with fatty acid-containing moieties. In some aspects, the disclosure provides compositions, such as pharmaceutical compositions, that include such modified small-molecule cytotoxins and a protein. In some embodiments, the protein is albumin or an albumin mimetic. Further, the disclosure provides various uses of these compounds and compositions.
>> Read More

BENZIMIDAZOLES FOR USE IN THE TREATMENT OF CANCER AND INFLAMMATORY DISEASES (Fri, 31 Mar 2017)
Provided herein are methods for treating, preventing, or ameliorating one or more symptoms of a condition, disorder, or disease mediated by a lipid kinase or a protein kinase with benzimidazoles, for example, of Formula I or II, and pharmaceutical compositions thereof. Also provided herein are benzimidazoles, and pharmaceutical compositions thereof; and methods of their use for treating, preventing, or ameliorating one or more symptoms of a proliferative disease.
>> Read More

COMPOSITIONS FOR PROMOTING READTHROUGH OF PREMATURE TERMINATION CODONS, AND METHODS OF USING THE SAME (Fri, 31 Mar 2017)
Disclosed are compounds of general formula (I) that promote readthrough of a premature termination codon (PTC) of an RNA molecule in a translation system, and their use, alone or in combination with other compounds, such as aminoglycoside, to treat diseases or disorders ameliorated by modulation of a premature termination codon (PTC) of an RNA molecule in a translation system. The disorder or disease may be Dystrophic epidermolysis bullosa, Batten disease, Duchenne muscular dystrophy, cancer, and spinal muscular atrophy. Ar-L-B (I)
>> Read More

NEW COMPOUNDS (Fri, 31 Mar 2017)
The invention relates to new quinoxaline, quinoline and quinazolinone 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.
>> Read More

BI-HETEROARYL SUBSTITUTED 1,4-BENZODIAZEPINES AND USES THEREOF FOR THE TREATMENT OF CANCER (Fri, 31 Mar 2017)
The invention relates to new quinoline, pyridopyrazine, naphthyridine and quinazolinone 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.
>> Read More

COMPOUNDS AND METHODS FOR INHIBITING JAK (Fri, 31 Mar 2017)
Disclosed are compounds of formula (I), pharmaceutical compositions comprising such compounds and methods/uses of using the same, for example, for treating a JAK-related disorder, such as cancer, cancer cachexia or an immune disorder: (I) wherein R1 is methyl or ethyl; R2 is selected from methyl, ethyl, methoxy and ethoxy; R3 is selected from hydrogen, chlorine, fluorine, bromine and methyl; R4 is selected from methyl, ethyl and -CH2OCH3; R5 and R6 are each individually methyl or hydrogen; and R7 is selected from methyl, ethyl, -(CH2)2OH and –(CH2)2OCH3, or a pharmaceutically acceptable salt thereof.
>> Read More

NANOPARTICLES FOR DIAGNOSIS AND DRUG DELIVERY (Fri, 31 Mar 2017)
The present invention relatesto a nanoparticle having a size comprised from 2 to 300 nm comprising: (i) a core comprising on its surface a noble metal selected from gold, silver or platinum, and (ii) an optionally positively charged amphiphilic linker comprising a hydrophobic C1-C20 alkyl thiolate moiety and a hydrophilic moietywhich is optionally hydrophilic positively charged. The invention also provides nanovectors comprising the nanoparticles of the invention and a compound of interest,such as a pharmaceutically active agent, in particular an anti-tumoral agent. Also provided are nanoparticles and nanovectors as defined above for diagnosis or for the prevention and/or treatment of a disease, in particular cancer.
>> Read More

METHOD OF SCREENING FOR AGENTS FOR DIFFERENTIATING STEM CELLS (Fri, 31 Mar 2017)
The present application discloses a method for identifying an agent for the treatment or prevention of cancer or metastatic cancer comprising the steps of contacting stem cell with a potential agent, and identifying an agent that induces differentiation, or inhibits stem cell pluripotency or growth of the stem cell, wherein such agent is determined to be an anti- cancer agent.
>> Read More

COMPOUND FOR TREATING BREAST CANCER AND PROGESTIN-DEPENDENT CONDITIONS (Thu, 30 Mar 2017)
This invention provides a pharmaceutical composition comprising a compound of formula S -(I): or its isomer, pharmaceutically acceptable salt, pharmaceutical product, crystal, N-oxide, hydrate or any combination thereof, for use in treating or preventing breast cancer in a subject.
>> Read More

PURINONE COMPOUNDS AS KINASE INHIBITORS (Thu, 30 Mar 2017)
Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. In addition, reversible inhibitors of Btk are also described. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.
>> Read More

Pyrrolidine-2, 5-dione derivatives, pharmaceutical compositions and methods for use as IDO1 inhibitors (Wed, 29 Mar 2017)
<p id="p-0001" num="0000">The present invention relates to compound of Formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.94mm" wi="34.88mm" file="US09603836-20170328-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> or pharmaceutically acceptable enantiomers, salts, solvates or prodrugs thereof. The invention further relates to the use of the compounds of Formula I as IDO1 inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer and endometriosis. The invention also relates to a process for manufacturing compounds of Formula I. </p>
>> Read More

PYRAZOLOPYRIMIDINE DERIVATIVES AS BTK INHIBITORS FOR THE TREATMENT OF CANCER (Fri, 24 Mar 2017)
This invention relates to novel compounds. The compounds of the invention are tyrosine kinase inhibitors. Specifically, the compounds of the invention are useful as inhibitors of Bruton's tyrosine kinase (BTK). The invention also contemplates the use of the compounds for treating conditions treatable by the inhibition of Bruton's tyrosine kinase, for example cancer, lymphoma, leukemia and immunological diseases.
>> Read More

NOVEL IMIDAZO [4,5-C] QUINOLINE AND IMIDAZO [4,5-C][1,5] NAPHTHYRIDINE DERIVATIVES AS LRRK2 INHIBITORS (Fri, 24 Mar 2017)
The present invention provides novel imidazo[4,5-c]quinoline and imidazo[4,5-c][1,5]naphthyridine derivatives of Formula (I), and the pharmaceutically acceptable salts thereof wherein R1, R1a, R1b, R2, R4, R5, R6, X and Z are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of Formula (I) and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.
>> Read More

1-PHENYLPYRROLIDIN-2-ONE DERIVATIVES AS PERK INHIBITORS (Fri, 24 Mar 2017)
The invention is directed to substituted pyrrolidinone and imidazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I: (I) wherein R1, R2, R3, R4, R5, R6, R7, X and Y are as defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases/injuries associated with activated unfolded protein response pathways, such as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson's disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt- Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
>> Read More

TRIAZOLONE COMPOUNDS AS PERK INHIBITORS (Fri, 24 Mar 2017)
The invention is directed to substituted triazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I: (I) wherein R1, R2, R3, R4, R5, X, Y, Y1, and Z are as defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes, as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
>> Read More

IMIDAZOLIDINONE DERIVATIVES AS INHIBITORS OF PERK (Fri, 24 Mar 2017)
The invention is directed to substituted imidazolidinone derivatives. Specifically, the invention is directed to compounds according to Formula I (I) wherein R1, R2, R3, R4, R5, R6, R7, X, Y1, Y2 and Z are defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes, as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
>> Read More

THERAPEUTIC COMBINATIONS OF A CD19 INHIBITOR AND A BTK INHIBITOR (Fri, 24 Mar 2017)
Therapeutic combinations of a CD 19 inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of a CD 19 inhibitor and a BTK inhibitor and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer, such as a hematological malignancy. A combination of a BTK inhibitor and a CD 19 inhibitor, such as a CD19-targeted antibody or a CD19-targeted chimeric antigen receptor expressing T cell or NK cell, and compositions and uses thereof are disclosed. Combinations of a BTK inhibitor and a CD 19 inhibitor with a programmed death- 1 (PD-1) or PD-1 ligand (PD-L1) inhibitor and compositions and uses thereof are also disclosed.
>> Read More

THE EXOCYST AS A NOVEL DRUG TARGET OF ENDOSIDIN2 AND APPLICATION AS A THERAPEUTIC (Fri, 24 Mar 2017)
A method of altering exocytosis in a plant or animal cell is provided. The method includes exposing the cell to a compound that binds to an EXO70 protein isoform. Also provided is a method of treating diabetes or cancer in a subject in need thereof, which includes administering to the subject an effective amount of a compound that binds to an EXO70 protein isoform. In addition, a method of screening for a substance that alters exocytosis in a plant or animal cell is provided, and analogs of compound Endosidin2 are also provided.
>> Read More

DNA BINDING AGENTS WITH A MINOR GROOVE BINDING TAIL (Fri, 24 Mar 2017)
Provided herein are compounds which intercalate into the DNA of a cell and are capable of crossing the blood brain barrier of a formula provided herein. Pharmaceutical compositions of the compounds and methods of treating cancer, for example brain, lung, or pancreatic cancer, are also provided herein.
>> Read More

PCNA INHIBITORS (Fri, 24 Mar 2017)
Described herein, inter alia, are compositions of PCNA modulators and methods for treating or preventing cancer.
>> Read More

CARBORANE COMPOUNDS AND METHODS OF USE THEREOF (Fri, 24 Mar 2017)
Disclosed herein are compounds comprising dicarba-closo-dodecaborane. The compounds can be, for example, estrogen receptor beta (ERβ) agonists. In some examples, the compounds can be selective ERβ agonists. Also provided herein are methods of treating, preventing, or ameliorating cancer in a subject, suppressing tumor growth in a subject, treating an inflammatory disease in a subject, treating a neurodegenerative disease in a subject, treating a psychotropic disorder in a subject, or a combination thereof, by administering to a subject a therapeutically effective amount of one or more of the compounds or compositions described herein, or a pharmaceutically acceptable salt thereof.
>> Read More

SULFINYLPHENYL OR SULFONIMIDOYLPHENYL BENZAZEPINES (Fri, 24 Mar 2017)
This invention relates to novel sulfinylphenyl or sulfonimidoylphenyl benzazepine compounds of the formula (I) wherein X and R1 to R6 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are TLR agonists and may therefore be useful as medicaments for the treatment of diseases such as cancer, autoimmune diseases, inflammation, sepsis, allergy, asthma, graft rejection, graft-versus-host disease, immunodeficiencies, and infectious diseases.
>> Read More

8-[6-[3-(AMINO)PROPOXY]-3-PYRIDYL]-1 -ISOPROPYL-IMIDAZO[4,5-C]QUINOLIN-2-ONE DERIVATIVES AS SELECTIVE MODULATORS OF ATAXIA TELANGIECTASIA MUTATED (ATM) KINASE FOR THE TREATMENT OF CANCER (Fri, 24 Mar 2017)
The specification generally relates to compounds of Formula (I): and pharmaceutically acceptable salts thereof, where Rl, R2, R3, R4 and R5 have any of the meanings defined herein. The specification also discloses the use of compounds of Formula (I) and salts thereof to treat or prevent ATM mediated disease, including cancer. The specification further relates to pharmaceutical compositions comprising substituted imidazo[4,5-c]quinolin-2-one compounds and pharmaceutically acceptable salts thereof; kits comprising such compounds and salts; methods of manufacture of such compounds and salts; and intermediates useful in such manufacture.
>> Read More

METHOD FOR PRODUCING MYCOSPORINE-LIKE AMINO ACID USING MICROBES (Thu, 23 Mar 2017)
Provided are: a method for producing a mycrosporine-like amino acid (MAA) that includes a step in which microbes are cultivated that produce MAA on the outside of bacterial cells, a step in which the bacterial cells and extracellular culture fluid are separated, and a step in which the MAA is recovered from the extracellular culture fluid; an MAA indicated by formula (1), an MAA produced using this method, or an ultraviolet-absorbing composition including the MAA indicated by formula (1); and a composition including the MAA produced using this method or the MAA indicated by formula (1), for preventing at least one symptom or disease selected from a group comprising acute skin reactions, aging of the skin, and skin cancer.
>> Read More

Indole compounds for use in treating inflammation and cancer (Wed, 22 Mar 2017)
<p id="p-0001" num="0000">Provided herein are compounds, comprising Formula (I) or Formula (II), and their pharmaceutically acceptable salts. Also provided are pharmaceutical compositions comprising a pharmaceutically acceptable excipient and at least one compound of Formula (I) and (II), singly or in combination with other pharmaceutically active ingredients, such as anti-inflammatory agents or anticancer agents. These compounds and pharmaceutical compositions are useful for treating inflammation or an inflammation related disorder in a subject via administration to the subject. These compounds and pharmaceutical compositions are also useful for inhibiting COX-2, for treating cancer, for reducing the size of a neoplasm, and for inhibiting tubulin polymerization in a cell.</p>
>> Read More

Heteroaryl Substituted Pyrrolo[2,3-B] Pyridines And Pyrrolo[2,3-B] Pyrimidines As Janus Kinase Inhibitors (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present invention provides heteroaryl substituted pyrrolo[2,3-b]pyridines and heteroaryl substituted pyrrolo[2,3-b]pyrimidines that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.</p>
>> Read More

Novel Imidazo[4,5-c]Quinoline And Imidazo[4,5-c][1,5]Naphthyridine Derivatives As LRRK2 Inhibitors (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present invention provides novel imidazo[4,5-c]quinoline and imidazo[4,5-c][1,5]naphthyridine derivatives of Formula (I), and the pharmaceutically acceptable salts thereof</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.02mm" wi="58.34mm" file="US20170073343A1-20170316-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, R<sup>1a</sup>, R<sup>1b</sup>, R<sup>2</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, X and Z are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of Formula (I) and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.</p>
>> Read More

ANTAGONISTS OF SLC38A9 AND THEIR USE IN THERAPY (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present invention relates to an antagonist or modulator of SLC38A9 for use in treating a disease associated with mTORC1 activation, like a proliferative disease (e.g. a cancerous disease or benign proliferative disease), a metabolic disorder, a disorder of the immune system, a disorder causing premature aging, an ophthalmic disorder or a neurological disorder. Exemplary diseases to be treated are cancerous diseases like lung cancer, breast cancer, bladder cancer, pancreatic cancer, ovarian cancer, colon carcinoma, leukemia, lymphoma, melanoma, esophageal cancer and stomach cancer; or metabolic disorders like overweight (pre-obesity), obesity or diabetes. Also provided herein are methods for treating, preventing or ameliorating such diseases comprising the administration of an antagonist of SLC38A9 to a subject in need of such a treatment, prevention or amelioration. Furthermore, the present invention provides methods for assessing the activity of a candidate molecule suspected of being an antagonist of SLC38A9 and identification of such antagonists.</p>
>> Read More

POLYETHYLENEIMINE POLYETHYLENEGLYCOL VECTORS (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">A polyplex of a double stranded RNA and a polymeric conjugate is provided, wherein the polymeric conjugate consists of a linear polyethyleneimine covalently linked to one or more polyethylene glycol (PEG) moieties, each PEG moiety being conjugated via a linker to a targeting moiety capable of binding to a cancer antigen.</p>
>> Read More

THIENO-INDOLE MOIETIES AND METHODS OF TREATING USING THE SAME (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present invention relates to a novel class of alkylating agents comprising a thieno-indole moiety linked to a DNA-binding moiety, which have cytotoxic activity and are useful in treating diseases such as cancer, cellular proliferation disorders and viral infections. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising them and methods of treating diseases utilizing such compounds or the pharmaceutical composition containing them. The invention also relates to the use of this novel class of alkylating agents in the preparation of conjugates.</p>
>> Read More

MCL-1 MODULATING COMPOUNDS FOR CANCER TREATMENT (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The invention relates to compounds of formula (I), and to their therapeutic use in the treatment of cancer:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="20.57mm" wi="61.04mm" file="US20170071921A1-20170316-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 Y<sub>1</sub>, Y<sub>2</sub>, Ar<sub>1</sub>, Ar<sub>2</sub>, R<sub>1</sub>, R<sub>2</sub>, i, j, k, l are as defined in claim <b>1. </b></li> </ul> </li> </ul> </p>
>> Read More

NOVEL DERIVATIVES OF OXAZAPHOSPHORINES AND THERAPEUTIC USES THEREOF (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present invention relates to novel derivatives of oxazaphosphorines, pharmaceutical compositions and therapeutic use thereof, in particular for treating or preventing cancer.</p>
>> Read More

Chelated PSMA Inhibitors (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">Compounds as defined herein are provided which are useful in (1) diagnostic methods for detecting and/or identifying cells presenting PSMA; (2) compositions comprising a compound of the invention together with a pharmaceutically acceptable diluent; and (3) methods for imaging prostate cancer cells.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.09mm" wi="75.18mm" file="US20170072075A1-20170316-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

CYCLOALKYL-HYDROXYL COMPOUNDS AND COMPOSITIONS FOR CHOLESTEROL MANAGEMENT AND RELATED USES (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present invention relates to novel cycloalkyl-hydroxyl compounds, compositions comprising hydroxyl compounds, and methods useful for treating and preventing a variety of diseases and conditions such as, but not limited to aging, Alzheimer's Disease, cancer, cardiovascular disease, diabetic nephropathy, diabetic retinopathy, a disorder of glucose metabolism, dyslipidemia, dyslipoproteinemia, hypertension, impotence, inflammation, insulin resistance, lipid elimination in bile, obesity, oxysterol elimination in bile, pancreatitis, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, Syndrome X, thrombotic disorder. Compounds and methods of the invention can also be used to modulate C reactive protein or enhance bile production in a patient. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.</p>
>> Read More

PYRIDINE DERIVATIVES (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present application provides novel pyridine compounds and pharmaceutically acceptable salts or prodrugs thereof. Also provided are methods for preparing these compounds. These compounds are useful in inhibiting CYP17 activity by administering a therapeutically effective amount of one or more of the compounds to a patient. By doing so, these compounds are effective in treating conditions associated with CYP17 activity. A variety of conditions can be treated using these compounds and include diseases which are characterized by abnormal cellular proliferation. In one embodiment, the disease is cancer, such as prostate cancer.</p>
>> Read More

FATTY ACID AMIDES, COMPOSITIONS AND METHODS OF USE (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The invention relates to fatty acid amides; compositions comprising an effective amount of a fatty acid amide; and methods for treating or preventing cancer, a metabolic disease or a neurodegenerative disease comprising the administration of an effective amount of a fatty acid amide.</p>
>> Read More

SUPRAMETALLOGELS AND USES THEREOF (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The disclosure provides nanostructures (e.g., nanospheres and nano-paddlewheels) formed through transition metal-ligand (e.g., Pd(II)-, Ni(II)-, or Fe(II)-ligand of Formula (A)) coordination and junction self-assembly. The disclosure also provides supramolecular complexes that include the nanostructures connected by divalent linkers Y. The provided supramolecular complexes are able to form gels (e.g., hydrogels). The gels are suprametallogels and exhibited excellent mechanical properties without sacrificing self-healing and showed high robustness and storage modulus. The present disclosure further provides compositions (e.g., gels) that include the nanostructures or supramolecular complexes and optionally an agent (e.g., small molecule), where the nanostructures and the nanostructure moieties of the supramolecular complexes may encapsulate and slowly release the agent. The nanostructures, supramolecular complex, and compositions may be useful in delivering an agent to a subject, tissue, or cell, as super-absorbent materials, and in treating a disease (e.g., a genetic diseases, proliferative disease (e.g., cancer or benign neoplasm), hematological disease, neurological disease, gastrointestinal disease (e.g., liver disease), spleen disease, respiratory disease (e.g., lung disease), painful condition, genitourinary disease, musculoskeletal condition, infectious disease, inflammatory disease, autoimmune disease, psychiatric disorder, or metabolic disorder).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="57.07mm" wi="51.05mm" file="US20170073311A1-20170316-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
>> Read More

GUANIDINE COMPOUNDS AND USE THEREOF (Fri, 17 Mar 2017)
<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

CARBAMATE COMPOUNDS AND METHODS OF MAKING AND USING SAME (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from indications such as pain, solid tumor cancer and/or obesity comprising administering a disclosed compound or composition.</p>
>> Read More

HETEROCYCLYL-BUTANAMIDE DERIVATIVES (Fri, 17 Mar 2017)
<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="21.59mm" wi="61.55mm" file="US20170073347A1-20170316-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which W, X and Y have the meanings indicated in Claim <b>1,</b> are inhibitors of Tankyrase, and can be employed, inter alia, for the treatment of diseases such as cancer, cardiovascular diseases, central nervous system injury and different forms of inflammation.</p>
>> Read More

BENZODIAZEPINE DIMERS, CONJUGATES THEREOF, AND METHODS OF MAKING AND USING (Fri, 17 Mar 2017)
<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="36.24mm" wi="69.93mm" file="US20170073357A1-20170316-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="74.34mm" wi="69.93mm" file="US20170073357A1-20170316-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

Humanized Monoclonal Antibodies and Methodsof Use (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present invention comprises a humanized monoclonal antibody that binds to the human immunoglobulin heavy chain variable region germline gene VH1-69. This antibody is derived from Mab G6 and recognizes the same epitope. Moreover, the antibody is used in combination with vaccines to augment an immune response to the antigen.</p>
>> Read More

PYRROLIDINE- SUBSTITUTED FLAVONE DERIVATIVES FOR PREVENTION OR TREATMENT OF ORAL MUCOSITIS (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present invention relates to the pyrrolidine substituted with flavone derivatives, represented by the compounds of Formula (I) (as described herein) or pharmaceutically acceptable salts, solvates, stereoisomers or diastereoisomers thereof or pharmaceutical compositions containing the compounds of Formula (I) for use in the prevention and/or treatment of oral mucositis caused by cancer therapy such as radiation therapy.</p>
>> Read More

RADIOLOGICALLY IDENTIFIED TUMOR HABITATS (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">Virtually every cancer patient is imaged with CT, PET or MRI. Importantly, such imaging reveals that tumors are complex and heterogeneous, often containing multiple habitats within them. Disclosed herein are methods for analyzing these images to infer cellular and molecular structure in each of these habitats. The methods can involve spatially superimposing two or more radiological images of the tumor sufficient to define regional habitat variations in two or more ecological dynamics in the tumor, and comparing the habitat variations to one or more controls to predict the severity of the tumor.</p>
>> Read More

COMPOSITIONS AND METHODS FOR DRUG-SENSITIZATION OR INHIBITION OF A CANCER CELL (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The disclosure provides rifamycin and rifamycin derivative compositions, including rifabutin and rifabutin derivative compositions able to cause drug-sensitization in a cancer cell or inhibition of a cancer cell. The disclosure also provides methods of administering such compositions to cancer cells to sensitize them to drugs, such as chemotherapeutics, or directly inhibit them. The disclosure also provides methods of administering such compositions to increase reactive oxygen species (ROS), particularly superoxides, in cancer cells. The disclosure further provides methods of determining whether a cancer will respond to chemotherapeutics and whether to administer rifamycin or a rifamycin derivative based on ROS levels in cancer cells of a patient.</p>
>> Read More

Xenoantigen-Displaying Anti-Cancer Vaccines and Method of Making (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">Compositions, methods of making, and methods of using, xenoantigen-displaying anti-cancer vaccines are described.</p>
>> Read More

Compositions and Methods for Controlled Localized Delivery of Bone Forming Therapeutic Agents (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present invention provides compositions and methods for providing controllable local delivery of a therapeutic agent to promote bone formation. In certain embodiments, the invention is used as a treatment for a subject with osteoporosis, bone cancer or bone fracture. The invention provides a therapeutic agent that is tethered to a polymer to form a therapeutic-tethered macromer, where the therapeutic agent is controllably released from the conjugate by degradation of the tether. In certain embodiments, the therapeutic agent is an inhibitor of GSK3β. In certain embodiments, the composition of the invention is specifically targeted to a site in need of bone formation or treatment.</p>
>> Read More

ANTI-ACTIVIN A ANTIBODIES AND USES THEREOF (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The disclosure provides compositions and methods relating to or derived from anti-activin A binding proteins, including antibodies. In particular embodiments, the disclosure provides fully human, humanized, and chimeric anti-activin A antibodies that bind human activin A, activin A-binding fragments and derivatives of such antibodies, and activin A-binding polypeptides comprising such fragments. Other embodiments provide nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having activin A-related disorders or conditions including cachexia related to gonadal cancer, other cancers, rheumatoid arthritis, and other diseases.</p>
>> Read More

NOVEL LYSYL TRNA SYNTHETASE FRAGMENT AND MICROVESICLES COMPRISING SAME (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present invention relates to: a lysyl tRNA synthetase (KRS) fragment which comprises an amino acid sequence represented by SEQ ID NO: 1 and is secreted from cancer cells; microvesicles comprising the KRS fragment; and a method for providing information necessary for cancer diagnosis and screening a cancer metastasis inhibiting agent using the same. The present invention can be favorably used in the development of a diagnostic kit for providing information necessary for cancer diagnosis or the development of a cancer metastasis inhibiting agent, and thus is highly industrially applicable.</p>
>> Read More

BH4 Antagonists and Methods Related Thereto (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The disclosure relates to BH4 inhibitors and therapeutic uses relates thereto. In certain embodiments, the disclosure relates to methods of treating or preventing cancer, such as lung cancer, comprising administering therapeutically effective amount of a pharmaceutical composition comprising a compound disclosed herein or pharmaceutically acceptable salt to a subject in need thereof.</p>
>> Read More

METHOD FOR TREATING A CANCER WITH A MIXED LIGAND GOLD(III) COMPLEXES AS ANTI-CANCER AGENTS (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">Gold(III) complexes with mixed ligands as anticancer agents. The gold(III) cations are coordinated to bidentate ligands having diamino functional groups: a diaminocyclohexane ligand and a 1,3-propylenediamine ligand. The diaminocyclohexane ligand can exist in both cis- and trans-configurations, resulting in isomeric gold(III) complexes. Also described are pharmaceutical compositions incorporating the gold(III) complexes, methods of synthesis, methods of treating cancer and methods of inhibiting cancer cell proliferation and inducing cancer cell apoptosis.</p>
>> Read More

CARTILAGE-HOMING PEPTIDES (Fri, 17 Mar 2017)
Peptides that home, target, migrate to, are directed to, are retained by, or accumulate in amd/or binds to the cartilage of a subject are disclosed. Pharmaceutical compositions and uses for peptides or peptide- active agent complexes comprising such peptides are also disclosed. Such compositions can be formulated for targeted delivery of a drug to a target region, tissue, structure or cell in the cartilage. Targeted compositions of the disclosure can deliver peptide or peptide- active agent complexes to target regions, tissues, structures or cells targeted by the peptide.
>> Read More

SYNTHETIC ANTIBODIES TO BAX AND USES THEREOF (Fri, 17 Mar 2017)
Synthetic fragment antigen-binding (Fab) antibodies are disclosed that bind to an N- terminal activation site of BCL-2-associated X-protein (BAX) and inhibit BAX activation. Also disclosed are methods of using the Fabs for measuring inactive monomeric BAX levels, screening for small molecules that bind to an N-terminal activation site of BAX, inhibiting apoptotic cell death, and predicting the ability of a cancer therapy to promote apoptotic cell death.
>> Read More

HETEROCYCLIC CONSTRAINED TRICYCLIC SULFONAMIDES AS ANTI-CANCER AGENTS (Fri, 17 Mar 2017)
A genus of arylsulfonamide derivatives of heterocyclic constrained tricyclic compounds is disclosed. The compounds are of the following genus: (I). The compounds induce FOXO1 transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a therapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.
>> Read More

HETEROCYCLIC CONSTRAINED TRICYCLIC SULFONAMIDES AS ANTI-CANCER AGENTS (Fri, 17 Mar 2017)
A genus of arylsulfonamide derivatives of heterocyclic constrained tricyclic compounds is disclosed. The compounds are of the following genus: The compounds induce FOXO1 transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a therapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed..
>> Read More

TRICYCLIC SULTAM SULFONAMIDES AS ANTICANCER AND NEUROPROTECTIVE AGENTS (Fri, 17 Mar 2017)
A genus of arylsulfonamide derivatives of heterocyclic constrained tricyclic compounds is disclosed. The compounds are of the following genus : The compounds induce FOXO1 transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a therapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.
>> Read More

RING CONSTRAINED DIARYLAMINO SULFONAMIDES AS ANTI-CANCER AGENTS (Fri, 17 Mar 2017)
A genus of arylsulfonamide derivatives of ring constrained diarylamino sulfonamide compounds is disclosed. The compounds are of the following genus:. The compounds induce FOXO1 transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a therapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.
>> Read More

CONSTRAINED BENZHYDRYL SULFONAMIDES AS ANTICANCER AND NEUROPROTECTIVE AGENTS (Fri, 17 Mar 2017)
A genus of arylsulfonamide derivatives of heterocyclic constrained tricyclic compounds is disclosed. The compounds are of the following genus: The compounds induce FOXO1 transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a therapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.
>> Read More

PEPTIDOMIMETIC MACROCYCLES AS MODULATORS OF MCL-1 (Fri, 17 Mar 2017)
The disclosed peptidomimetic macrocycles such as Formula (Ic) that can modulate the activity of MCL-1. Myeloid cell leukemia 1 (MCL-1) is a protein that inhibits cell death. Peptidomimetic macrocycles, pharmaceutical compositions, and methods disclosed herein can be used for the treatment of disease in which MCL-1 is over-expressed, such as cancer. In particular, MCL- 1 -modulating peptidomimetic macrocycles disclosed herein can be applied in the setting of resistance to BCL-2 family inhibitors, which is often engendered by MCL-1 over-expression or hyperactivation.
>> Read More

SALTS OF A PIM KINASE INHIBITOR (Fri, 17 Mar 2017)
The present invention relates to salt forms of the Pim kinase inhibitor N-{(7R)-4- [(3R,4R,5S)-3-amino-4-hydroxy-5-methylpiperidin-1-yl]-7-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl}-6-(2,6-difluorophenyl)-5- fluoropyridine-2-carboxamide, including methods of preparation thereof, and intermediates in the preparation thereof, where the compound is useful in the treatment of Pim kinase-related diseases such as cancer.
>> Read More

CYANO THIENOTRIAZOLODIAZEPINES AND USES THEREOF (Fri, 17 Mar 2017)
The present invention provides compounds and pharmaceutically compositions thereof. The compounds and compositions are binders of bromodomains and/or bromodomain-containing proteins (e.g., bromo and extra terminal (BET) proteins). Also provided are methods, uses, and kits using the compounds and pharmaceutical compositions for inhibiting the activity (e.g., increased activity) of bromodomains and/or bromodomain-containing proteins and for treating and/or preventing in a subject diseases associated with bromodomains or bromodomain-containing proteins (e.g., proliferative diseases, cardiovascular diseases, viral infections, fibrotic diseases, metabolic diseases, endocrine diseases, and radiation poisoning). The compounds, pharmaceutical compositions, and kits are also useful for male contraception.
>> Read More

INHIBITORS OF CYCLIN-DEPENDENT KINASES (Fri, 17 Mar 2017)
The present invention provides novel compounds of Formulae (I'), (I), (II'), and (II), 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 and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with 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, such as a cyclin-dependent kinase (CDK) (e.g., CDK7, CDK12, or CDK13), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.
>> Read More

HISTONE DEMETHYLASE INHIBITORS (Fri, 10 Mar 2017)
<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 prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.</p>
>> Read More

HETEROARYL COMPOUNDS AND THEIR USE AS THERAPEUTIC DRUGS (Fri, 10 Mar 2017)
<p id="p-0001" num="0000">The present invention provides heterocyclic compounds, the stereoisomer thereof, the enantiomer thereof, or the pharmaceutically acceptable salt, which are capable of modulating the activity of Mer receptor tyrosine kinase (MERTK). This invention also provides pharmaceutical compositions thereof, methods to prepare the said compounds, and the use of such compounds as a medicament.</p> <p id="p-0002" num="0000">The present invention is directed to MERTK inhibitory compounds with marked potency, thereby having an outstanding potential for a pharmaceutical intervention of cancer and any other diseases related to MERTK dysregulation.</p>
>> Read More

Site Search