Cancer

BISPHENOL DERIVATIVES AND THEIR USE AS ANDROGEN RECEPTOR ACTIVITY MODULATORS (Fri, 20 Oct 2017)
Compounds having a structure of Formula I or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1, R2, R3, R11a, R11b, R11c, R11d, and X, are as defined herein, are provided. Uses of such compounds for modulating androgen receptor activity, imaging diagnostics in cancer and therapeutics, and methods for treatment of subjects in need thereof, including prostate cancer are also provided.
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BROMODOMAIN INHIBITORS (Fri, 20 Oct 2017)
The present invention provides for compounds of formula (I) wherein R1, R2, R3, R4, R6, X1, and X2 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising compounds of formula (I).
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HETEROCYCLIC COMPOUNDS AS RET KINASE INHIBITORS (Fri, 20 Oct 2017)
The present invention relates to compounds of Formula I that function as inhibitors of RET (rearranged during transfection) kinase enzyme activity: wherein HET, bonds a, b, c and d, X1, X2, X3, X4, R2, and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which RET kinase activity is implicated.
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HETEROCYCLIC COMPOUNDS AS RET KINASE INHIBITORS (Fri, 20 Oct 2017)
The present invention relates to compounds of formula I that function as inhibitors of RET (rearranged during transfection) kinase enzyme activity: wherein HET, X1, X2, X3, X4, integer a and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which RET kinase activity is implicated.
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AIE NANOPARTICLE CONJUGATES AND METHODS THEREFOR (Fri, 20 Oct 2017)
Described are compositions comprising amphiphilic polymer nanoparticles, such as DSPE-PEG, encapsulating a photostable agent with aggregation-induced emission (AIE) characteristic. The photostable AIE agents are preferably small organic molecules with tetraphenylethylene moieties. The nanoparticles are synthesized by a modified nanoprecipitation method and the size of the nanoparticles is controlled by varying the loading ratio, the solvent ratio and the tatio of hydrophilic to hydrophobic length of the polymer. The nanoparticles are surface modified with a conjugatable group for covalently linking to at least one targeting moiety, such as antibodies or affibodies to IgG, EGFR and Her2. Methods for immunostaining or imaging or detecting or tracking a live cell, such as cancer cells, using the nanoparticle compositions are described.
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IMIDAZO[1,2-A]PYRIDINE COMPLEXES WITH ANTICANCER ACTIVITY (Fri, 20 Oct 2017)
This invention relates to a metal complex of an imidazo[l,2-a]pyridine ligand and/or a metal complex of an imidazo[l,2-a] pyridine ligand derivative and/or an analogue thereof, wherein said metal complexes are for use in treating cancer. Typically, the cancer is breast cancer, colorectal cancer, colon cancer, and/or leukemia.
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TG2 INHIBITOR COMPOUNDS AND USES THEREOF (Fri, 20 Oct 2017)
There are provided Tissue Transglutaminase (TG2) inhibitor compounds, and compositions and methods of use thereof for the prevention or treatment of a cancer. Compounds of Formula I, and pharmaceutically acceptable salts thereof, are provided: Formula (I).
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ENANTIOENRICHED VIRIDICATUMTOXIN B ANALOGS (Fri, 20 Oct 2017)
In one aspect, the present disclosure provides derivatives of viridicatumtoxin of the formula wherein the variables are as defined herein. Also provided herein are compositions and methods of treating a bacterial infection, a viral infection, or in the treatment of cancer. The present disclosure also provides methods of synthesizing enantiopure viridicatumtoxin and other anthrone compounds.
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BET PROTEIN DEGRADERS (Fri, 20 Oct 2017)
The present disclosure provides compounds represented by Formula I: and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein B, R1, R5, Q1, Q", L, X, Y, and Z are as defined as set forth in the specification. The present disclosure also provids compounds of Formula I for use to treat a condition or disorder responsive to degradation of BET bromodomains such as cancer.
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FOCUSED INTERFERON IMMUNOTHERAPY (Fri, 20 Oct 2017)
The present invention relates to methods of treating a proliferative disease (such as cancer) in an individual, comprising administering to the individual a non-naturally occurring fusion molecule comprising an antibody against one or more tumor-associated antigen ("TAA Ab") attached to an interferon (IFN) molecule (hereinafter "TAA Ab-IFN fusion molecule"), as monotherapy at therapeutically effective low doses, or in combination with immunotherapy, wherein the combination therapy provides increased effector cell killing. The methods of the present invention are particularly effective treating recurrent, resistant, or refractory proliferative diseases.
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SMALL MOLECULES FOR IMMUNOGENIC TREATMENT OF CANCER (Fri, 20 Oct 2017)
The present invention relates to new compounds for immunogenic treatment of cancer. The compounds can be administered as a single agent or in combination with an anticancer drug including modulators of other immune pathways, especially immune checkpoint inhibitors that target CTLA-4, PD-1, and PD-L1 proteins. The compounds can produce neoantigens through irreversible protein binding in cancer cells and generate immune response.
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NEUROTENSIN RECEPTOR BINDING CONJUGATES AND FORMULATIONS THEREOF (Fri, 20 Oct 2017)
Conjugates of an active agent attached to a neurotensin receptor-binding targeting moiety via a linker have been designed. Nanoparticles and microparticles comprising such conjugates can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or other diseases.
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METHODS FOR MONITORING AND TREATING CANCER (Fri, 20 Oct 2017)
The present invention provides therapeutic and diagnostic methods and compositions for cancer. The invention provides, inter alia, methods of treating cancer and methods of monitoring the response of a patient having a cancer to treatment with a VEGF antagonist (e.g., an anti-VEGF antibody).
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METHODS FOR MONITORING AND TREATING CANCER (Fri, 20 Oct 2017)
The present invention provides therapeutic and diagnostic methods and compositions for cancer, for example, kidney cancer. The invention provides, inter alia, methods of treating cancer and methods of monitoring the response of a patient having a cancer to treatment with an anti-cancer therapy comprising a VEGF antagonist (e.g., an anti-VEGF antibody) and a PD-L1 axis binding antagonist (e.g., an anti-PD-L1 antibody).
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METHODS AND COMPOSITIONS FOR DETECTION AND DIAGNOSIS OF BREAST CANCER (Fri, 20 Oct 2017)
The present disclosure provides methods, compositions and kits for the detection and diagnosis of breast cancer.
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PHARMACEUTICAL COMPOSITION HAVING BICYCLIC NITROGEN-CONTAINING AROMATIC HETEROCYCLIC AMIDE COMPOUND AS ACTIVE COMPONENT (Thu, 19 Oct 2017)
[Problem] Provided is a pharmaceutical composition for treating lung cancer involving mitochondrial Complex I, particularly non-small cell lung cancer. [Solution] After investigating compounds having a mitochondrial Complex I inhibitory effect, the present inventor completed the present invention by confirming that the bicyclic nitrogen-containing aromatic heterocyclic amide compounds of the present invention have a mitochondrial Complex I inhibitory effect, and that these compounds have an antitumor effect on mice carrying cancer derived from non-small cell lung cancer.
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PHARMACEUTICAL COMPOSITION HAVING BICYCLIC NITROGEN-CONTAINING AROMATIC HETROCYCLIC AMIDE COMPOUNDS AS ACTIVE INGREDIENT (Thu, 19 Oct 2017)
[Problem] To provide a pharmaceutical composition for treating various cancers in which mitochondrial complex I is involved, in particular, colon cancer, leukemia and/or malignant lymphoma. [Solution] With the invention of creating pharmaceutical compositions for treating various cancers, the inventors confirmed, on the basis of the result of intensive investigation, that pharmaceutical compositions, which contain specific bicyclic nitrogen-containing aromatic heterocyclic amide compounds having an AMPK activation effect and mitochondrial complex I is involved, in particular, colon cancer, leukemia and/or malignant lymphoma; thereby completing the present invention.
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NOVEL 4-(ARYL)-N-(2-ALKOXYTHIENO[3,2-B]PYRAZIN-3-YL)-PIPERAZINE-1-CARBOXAMIDE DERIVATIVE, AND ANTIPROLIFERATIVE EFFECT THEREOF (Thu, 19 Oct 2017)
The present invention relates to a novel 4-(aryl)- N- (2-alkoxythieno[3,2-b]pyrazin-3-yl)-piperazin-1-carboxamide derivative compound useful in the prevention or treatment of cancer; a preparation method thereof; and a pharmaceutical composition comprising the same. The novel 4-(aryl)- N- (2-alkoxythieno[3,2-b]pyrazin-3-yl)-piperazin-1-carboxamide derivative compound of the present invention can effectively inhibit the growth of proliferating cells, and thus can be useful in the prevention or treatment of cancer.
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BIPYRAZOLE SALT AS JAK INHIBITOR (Thu, 19 Oct 2017)
The present invention provides compounds of Formula I: or pharmaceutically acceptable salts thereof, as well as their compositions and methods of use, that inhibit the activity of Janus kinase (JAK) and are useful in the treatment of diseases related to the activity of JAK including, for example, inflammatory disorders, autoimmune disorders, cancer, and other diseases.
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N,N-DIMETHYL-3-[[5-(3-METHYL-2-OXO-1-TETRAHYDROPYRAN-4-YL-IMIDAZO[4,5-C]QUINOLIN-8-YL)-2-PYRIDYL]OXY]PROPAN-1-AMINE OXIDE AS ATM (ATAXIA TELANGIECTASIA MUTATED) KINASE MODULATOR FOR TREATING CANCER (Fri, 13 Oct 2017)
The specification generally relates to the compound of Formula (I), i.e. to N,N-dimethyl-3-[[5-(3-methyl-2-oxo-l-tetrahydropyran-4-yl-imidazo[4,5-c]quinolin-8-yl)-2-pyridyl]oxy]propan-l-amine oxide as ATM (ataxia telangiectasia mutated) kinase modulator for treating cancer.
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MDR-REVERSING 8-HYDROXY-QUINOLINE DERIVATIVES (Fri, 13 Oct 2017)
The present invention is related to 8-hydroxy-quinoline derivatives having multidrug-resistance reversing activity with improved selectivity and increased cytotoxicity towards multidrug-resistant cancer cells, preparation thereof and use of the same in the treatment of cancer, especially multidrug-resistant variants thereof.
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CRYSTALLINE FORMS OF LORLATINIB MALEATE (Fri, 13 Oct 2017)
This invention relates to new crystalline forms of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3- h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile(lorlatinib) maleate. The invention also relates to pharmaceutical compositions comprising lorlatinib maleate, and to methods of using lorlatinib maleate and compositions comprising it in the treatment of abnormal cell growth, such as cancer,in mammals.
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MACROCYCLIC INHIBITORS OF THE PD-1/PD-L1 AND CD80/PD-L1 PROTEIN/PROTEIN INTERACTIONS (Fri, 13 Oct 2017)
The present disclosure provides novel macrocyclic peptides which inhibit the PD-1/PD-Ll and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases. wherein: A is selected from a bond.
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METHODS OF TREATING PEDIATRIC CANCERS (Fri, 13 Oct 2017)
A method of treating a pediatric cancer in a subject in need thereof. The method includes administering to the subject a therapeutically effective amount of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, or a pharmaceutically acceptable salt thereof, or a combination thereof.
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LIQUID FORMULATIONS OF (S)-N-(5-((R)-2-(2,5-DIFLUOROPHENYL)-PYRROLIDIN-1-YL)-PYRAZOLO[1,5-A]PYRIMIDIN-3-YL)-3-HYDROXYPYRROLIDINE-1-CARBOXAMIDE (Fri, 13 Oct 2017)
A liquid formulation of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutically acceptable salts thereof, or a combination thereof and the use of the liquid formulation in the treatment of pain, cancer, inflammation, and certain infectious diseases are disclosed.
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LLS COMPOUNDS FOR TREATMENT OF CANCER (Fri, 13 Oct 2017)
The present invention provides benzamidazole compounds and methods of using the compounds as galectin-1 inhibitors.
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MDM2 PROTEIN DEGRADERS (Fri, 13 Oct 2017)
The present disclosure provides compounds represented by Formula I-A: A1− L 1−B1 I-A and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein A1, B1, and L1 are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I-A for use to treat a condition or disorder responsive to degradation of MDM2 protein such as cancer.
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SMALL MOLECULE REGULATORS OF STEROID RECEPTOR COACTIVATORS AND METHODS OF USE THEREOF (Fri, 13 Oct 2017)
Small molecule regulators of steroid receptor coactivator (SRC) family proteins are provided, as well as methods for their use in treating or preventing SRC-related diseases. The SRC-related diseases can include cancer, metabolic disorders, human immunodeficiency virus, neurodegenerative disorders, and/or inflammatory diseases. Also provided are methods for regulating SRC family proteins in a cell.
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PYRIMIDO-DIAZEPINONE KINASE SCAFFOLD COMPOUNDS AND METHODS OF TREATING PI3K-MEDIATED DISORDERS (Fri, 13 Oct 2017)
The present invention relates to use of pyrimido-diazepinone compounds that are able to modulate protein kinases such as ΡΙ3Κ-γ and PI3K-δ, which are members of the Class I Type IA and Class I Type IB family of phosphatidylinositol- 4,5-bisphosphate 3-kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.
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PRODIGIOSIN ANALOGS (Fri, 13 Oct 2017)
Prodigiosin analogs which reactivate the p53 pathway are provided, as well as compositions of these compounds, and methods for reactivation of the p53 pathway using these compounds are provided. The prodigiosin analogs may be used to treat cancer in which p53 mutation plays a role, including prostate cancer, breast cancer, kidney cancer, ovarian cancer, lymphoma, leukemia, and glioblastoma, among others.
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METHODS AND COMPOSITIONS FOR CAR T CELL THERAPY (Fri, 13 Oct 2017)
The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.
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Method of isolating phenanthroindolizidine alkaloids from <i>Tylophora atrofolliculata </i>with HIF-1 inhibitory activity, compositions comprising them and their use (Wed, 11 Oct 2017)
<p id="p-0001" num="0000">A method of isolating at least one phenanthroindolizidine alkaloid, in particular with HIF-1 inhibitory activity, from <i>Tylophora atrofolliculata </i>is used to isolate and obtain for example about 22 phenanthroindolizidine alkaloids, including at least 11 new phenanthroindolizidine alkaloids which have not been previously isolated. Experimental tests confirmed an exceptional HIF-1 inhibitory activity of the phenanthroindolizidine alkaloids isolated. A pharmaceutical composition includes at least one phenanthroindolizidine alkaloid and at least one pharmaceutical tolerable excipient. A method of treating a subject suffering from cancer includes administering at least one phenanthroindolizidine alkaloid isolated from <i>Tylophora atrofolliculata</i>. A method of treating a subject suffering from cancer includes administering at least one phenanthroindolizidine alkaloid to the subject.</p>
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METHODS OF TREATING PEDIATRIC CANCERS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">A method of treating a pediatric cancer in a subject in need thereof. The method includes administering to the subject a therapeutically effective amount of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, or a pharmaceutically acceptable salt thereof, or a combination thereof.</p>
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Pyrido-, Pyrazo- and Pyrimido-Pyrimidine Derivatives as mTOR Inhibitors (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">There is provided a compound of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.27mm" wi="55.88mm" file="US20170281637A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt thereof. There are also provided processes for the manufacture of a compound of Formula 1, and the use of a compound of Formula 1 as a medicament and in the treatment of cancer.</p>
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CYCLIC UREA COMPOUNDS AS TROPOMYOSIN-RELATED KINASE (TRK) iNHIBITORS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Tropomyosin-related kinase inhibitors (Trk inhibitors) are small molecule compounds useful in the treatment of disease. Trk inhibitors can be used as pharmaceutical agents and in pharmaceutical compositions. Trk inhibitors are useful in the treatment of inflammatory diseases, autoimmune disease, defects of bone metabolism and/or cancer, and are particularly useful in the treatment of osteoarthritis (OA), pain, and pain associated with OA. Trk inhibitors are also useful for inhibiting tropomyosin-related kinase A (TrkA), tropomyosin-receptor kinase B (TrkB), tropomyosin-receptor kinase C (TrkC), and/or c-FMS (the cellular receptor for colony stimulating factor-1 (CSF-1)).</p>
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USE OF THIOPYRIMIDINECARBOXAMIDE FOR TREATING CANCER (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">There is disclosed is a method of treating disease using compound having formula SX-682</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="52.32mm" wi="69.85mm" file="US20170281659A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">alone or in combination with an antineoplastic agent, microtubule affecting agents, antineoplastic agents, anti-angiogenesis agents, VEGF receptor kinase inhibitors, antibodies against the VEGF receptor, interferon, or radiation.</p>
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COMBINED CANCER THERAPY WITH IMMUNE CHECKPOINT MODULATORS AND FERMENTATION PRODUCTS BY SYMBIOTIC MICROBIOTA (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Combined therapy of cancer using an immune check point modulators (e.g., an immune checkpoint inhibitor) and a fermented product, which may be prepared using symbiotic microbiota.</p>
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PHARMACEUTICAL COMPOSITIONS AND THEIR USE FOR TREATMENT OF CANCER AND AUTOIMMUNE DISEASES (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Described herein are combination therapies for cancer (such as lymphoid malignancies) and immune diseases (such as autoimmune diseases and inflammatory diseases). The therapies comprise the combined use of inhibitors of BTK, mTOR kinase, and Bcl-2 or their signaling pathways, and immunomodulatory drugs. Also described are pharmaceutical compositions and kits comprising these inhibitors.</p>
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DERIVATIVES OF MACROCYCLIC N-ARYL-2-AMINO-4-ARYL-PYRIMIDINE POLYETHERS AS INHIBITORS OF FTL3 AND JAK (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention relates to a compound with the following formula: formula (I) or a salt and/or a pharmaceutically acceptable solvate thereof, in particular for use as a drug, in particular in the treatment of cancer, as well as to the pharmaceutical compositions that contain same and to the methods for preparing same.</p>
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ANDROGEN RECEPTOR MODULATORS AND METHODS FOR THEIR USE (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Compounds having a structure of Structure I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.64mm" wi="49.70mm" file="US20170283377A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>6</sup>, Y<sup>1 </sup>and Y<sup>2 </sup>are as defined herein, and wherein at least one of R<sup>3 </sup>or R<sup>4 </sup>is a straight-chain C<sub>1</sub>-C<sub>6 </sub>haloalkyl, are provided. Uses of such compounds for treatment of various indications, including prostate cancer, as well as methods of treatment involving such compounds are also provided.</p>
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Bruton's Tyrosine Kinase Inhibitors (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. 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 diseeases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.78mm" wi="53.68mm" file="US20170283393A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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2-AMINOPYRIMIDINE COMPOUND AND PHARMACEUTICAL COMPOSITION AND USE THEREOF (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Disclosed are a 2-aminopyrimidine compound and pharmaceutical composition and use thereof. The structure of the 2-aminopyrimidine compound is as represented by formula I, in the formula, R<sub>1</sub>, R<sub>2</sub>, R<sub>3</sub>, R<sub>4</sub>, R<sub>5</sub>, X, Y, Z, W, (i) being as defined in the specification and the claims. Such compounds effectively inhibit the growth of a variety of tumor cells and have inhibitory effects on EGFR and IGF1R protease, and can be used for preparing antineoplastic drugs and overcome the tolerance induced by the existing drugs such as gefitinib, erlotinib and the like. The compound has selectivity for tumors, in particular the wild-type non-small cell lung cancer and have good pharmacokinetic characteristics.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="65.02mm" wi="66.04mm" file="US20170283398A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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THERAPEUTIC COMPOSITIONS AND RELATED METHODS OF USE (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Compositions comprising compounds that modulate pyruvate kinase M2 (PKM2) are described herein. Also described herein are methods of using the compounds that modulate PKM2 in the treatment of cancer.</p>
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BENZO-HETEROCYCLIC COMPOUNDS AND THEIR APPLICATIONS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention relates to benzoxazole derivatives having the following Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.72mm" wi="57.07mm" file="US20170283408A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The compounds of the present invention are found to possess the ability to decrease PD-L1 level, suggesting that the compounds of the invention can be used in cancer immunotherapy and treatment or prevention of sepsis or septic shock.</p>
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PYRIMIDO-DIAZEPINONE COMPOUNDS AND METHODS OF TREATING DISORDERS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention relates to novel pyrimido-diazepinone compounds, methods of modulating protein kinases, including MPS1 (TTK), ERK5 (BMK1, MAPK7), LRKK2, EphA2, polo kinase 1, 2, 3, or 4, Ack1, Ack2, Abl, DCAMKL1, ABL1, Abl mutants, DCAMKL2, ARK5, BRK, MKNK2, FGFR4, TNK1, PLK1, ULK2, PLK4, PRKD1, PRKD2, PRKD3, ROS1, RPS6KA6, TAOK1, TAOK3, TNK2, Bcr-Abl, GAK, cSrc, TPR-Met, Tie2, MET, FGFR3, Aurora, Axl, Bmx, BTK, c-kit, CHK2, Flt3, MST2, p70S6K, PDGFR, PKB, PKC, Raf, ROCK-H, Rsk1, SGK, TrkA, TrkB and TrkC, and the use of such compounds in the treatment of various diseases, disorders or conditions.</p>
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NOVEL COMPOSITIONS AND THERAPEUTIC METHODS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention is directed to novel products, variants, pharmaceutically acceptable salts and prodrugs thereof, and medical use of such compounds for the treatment and/or management of sepsis, septicemia, septic shock, ocular infection, ocular inflammation, ocular angiogenesis, rheumatoid arthritis (RA), atherosclerosis, inflammatory bowel diseases (IBD), asthma, chronic obstructive pulmonary disease, fever syndromes, cachexia, psoriasis, autoimmune diseases, cardiac diseases, retinoblastoma, cancer and/or any disorder associated with inflammation, immunomodulation and microbial infection.</p>
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Benzoquinone Derivatives For Treatment Of Cancer And Methods Of Making The Benzoquinone Derivatives (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention benzoquinone derivatives of the formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.38mm" wi="21.34mm" file="US20170283366A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and to pharmaceutically acceptable salts or solvates thereof. In formula (I) one of X or Y is hydrogen and the other one of X or Y is 3-Trifluoro-methylaniline; 3,4,5-trifluoroaniline; 4-methoxylaniline; 4-fluoroaniline; 3,3′-Dimethyl-1,1′-Biphenyl-4,4′-diamine; 2-(pyrrolidin-l-yl)ethyl)amine; 4-trifluoromethyl-benzylamine ; 4-fluorobenzyl-amine; 3,4-dimethoxybenzylamine; or 3,5-ditrifluoromethyl-benzylamine. Compounds of formula (I) have been identified as being useful in the treatment of cancer, in particular lung, breast and pancreatic cancer. The invention relates also to a method of making the benzoquinone derivatives and to methods of treatment.</p>
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COMPOSITIONS AND METHODS FOR TREATMENT OF PROSTATE CARCINOMA (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Disclosed herein are 1,4-naphthoquinone analogs, pharmaceutical compositions that include one or more of such 1,4-naphthoquinone analogs, and methods of treating and/or ameliorating diseases and/or conditions associated with a cancer, such as prostate cancer with such 1,4-naphthoquinone analogs. Also included are combination therapies wherein a 1,4-naphthoquinone analog disclosed herein, and a hormone therapy agent are provided to a subject suffering from a condition such as cancer.</p>
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INDOLE DERIVATIVES FOR THE PREVENTION AND/OR TREATMENT OF DIABETES AND ASSOCIATED METABOLIC DISORDERS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The invention relates to substituted heterocyclic indole derivatives of Formula (I), which act as activators of the AMP-activated protein kinase (AMPK) and to the use of them for the treatment and prevention of diseases or disorders regulated by AMPK. As a result, these compounds can be used for the treatment of inflammatory, autoimmune, cardiovascular, neurological diseases and cancer.</p>
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CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Chemical entities that are quinoxaline kinase inhibitors, pharmaceutical compositions and methods of treatment of cancer are described.</p>
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COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described, wherein the compounds have formula Ia:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.46mm" wi="62.48mm" file="US20170283423A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC kinase protein. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC, including rheumatoid arthritis, osteoarthritis, osteoporosis, peri-prosthetic osteolysis, systemic sclerosis, demyelinating disorders, multiple sclerosis, Charcot Marie Tooth syndrome, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, global ischemia, ulcerative colitis, Crohn's disease, immune thrombocytopenic purpura, atherosclerosis, systemic lupus erythematosis, myelopreparation for autologous transplantation, transplant rejection, glomerulonephritis, interstitial nephritis, Lupus nephritis, tubular necrosis, diabetic nephropathy, renal hypertrophy, type I diabetes, acute pain, inflammatory pain, neuropathic pain, acute myeloid leukemia, melanoma, multiple myeloma, breast cancer, prostate cancer, pancreatic cancer, lung cancer, ovarian cancer, gliomas, glioblastoma, neurofibromatosis, osteolytic bone metastases, brain metastases, gastrointestinal stromal tumors, and giant cell tumors.</p>
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MACROCYCLIC COMPOUNDS AS TRK KINASE INHIBITORS (Fri, 06 Oct 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>, R<sup>3a</sup>, and Z 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="33.70mm" wi="57.07mm" file="US20170283435A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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TRITERPENE SAPONINS, METHODS OF SYNTHESIS AND USES THEREOF (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention relates to triterpene glycoside saponin-derived adjuvants, syntheses thereof, intermediates thereto, and uses thereof. QS-7 is a potent immuno-adjuvant that is significantly less toxic than QS-21, a related saponin that is currently the favored adjuvant in anticancer and antiviral vaccines. Tedious isolation and purification protocols have hindered the clinical development of QS-7. A novel semi-synthetic method is provided wherein a hydrolyzed prosapogenin mixture is used to synthesize QS-7, QS-21, and related analogs, greatly facilitating access to QS-7 and QS-21 analogs for preclinical and clinical evaluation.</p>
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IMMUNOMODULATORS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present disclosure provides novel macrocyclic peptides which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.</p>
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IMMUNOMODULATORS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present disclosure provides novel macrocyclic peptides which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.</p>
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CANCER VACCINE COMPOSITIONS AND METHODS OF USE THEREOF (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present application describes compositions that include an epitope of a peptide that elicits an immune response in a subject following administration. The compositions described herein include nucleic acids. The present application also describes compositions that include peptides. Also described herein are methods that include administering a composition comprising an epitope of a peptide to a subject in need thereof.</p>
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DERIVATIVES OF MACROCYCLIC N-ARYL-TRICYCLOPYRIMIDINE-2-AMINE POLYETHERS AS INHIBITORS OF FTL3 AND JAK (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention relates to a compound with the following formula (I): (I) or a salt and/or a pharmaceutically acceptable solvate thereof, in particular for use as a drug, in particular in the treatment of cancer, as well as to the pharmaceutical compositions that contain same and to the methods for preparing same.</p>
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BCMA BINDING MOLECULES AND METHODS OF USE THEREOF (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The invention provides antibodies, antigen binding fragments thereof, chimeric antigen receptors (CARs), and engineered T cell receptors, polynucleotides encoding the same, and in vitro cells comprising the same. The polynucleotides, polypeptides, and in vitro cells described herein can be used in an engineered CAR T cell therapy for the treatment of a patient suffering from a cancer. In one embodiment, the polynucleotides, polypeptides, and in vitro cells described herein can be used for the treatment of multiple myeloma.</p>
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METHODS FOR DETECTING OVARIAN CANCER (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present description is related to the field of ovarian cancer diagnostics. It introduces novel biomarkers that can be used to detect presence of ovarian cancer and to provide a prognosis of the disease.</p>
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MODULATION OF GLOBOSERIES GLYCOSPHINGOLIPID SYNTHESIS AND CANCER BIOMARKERS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present disclosure relates to methods and compositions which can modulate the globoseries glycosphingolipid synthesis. Particularly, the present disclosure is directed to glycoenzyme inhibitor compound and compositions and methods of use thereof that can modulate the synthesis of globoseries glycosphingolipid SSEA-3/SSEA-4/GloboH in the biosynthetic pathway; particularly, the glycoenzyme inhibitors target the alpha-4GalT; beta-4GalNAcT-I; or beta-3GalT-V enzymes in the globoseries synthetic pathway. Additionally, the present disclosure is also directed to vaccines, antibodies, and/or immunogenic conjugate compositions targeting the SSEA-3/SSEA-4/GLOBO H associated epitopes (natural and modified) which elicit antibodies and/or binding fragment production useful for modulating the globoseries glycosphingolipid synthesis. Moreover, the present disclosure is also directed to the method of using the compositions described herein for the treatment or detection of hyperproliferative diseases and/or conditions. Furthermore, the instant disclosure also relates to cancer stem cell biomarkers for diagnostic and therapeutic uses.</p>
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PURINE INHIBITORS OF HUMAN PHOSPHATIDYLINOSITOL 3-KINASE DELTA (Fri, 06 Oct 2017)
The instant invention provides compounds of formula (I) which are PI3K-delta inhibitors, and as such are useful for the treatment of PI3K-delta-mediated diseases such as inflamation, asthma, COPD and cancer.
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METHODS FOR SELECTING ANTIBODIES THAT SPECIFICALLY BIND GLYCOSYLATED IMMUNE CHECKPOINT PROTEINS (Fri, 06 Oct 2017)
Methods for producing and screening for antibodies that specifically bind to glycosylated immune checkpoint proteins (ICPs) relative to non-glycosylated ICPs are provided. Such antibodies recognize specific epitopes of glycosylated ICPs and can prevent or block the binding of a glycosylated ICP with its ligand, such as another ICP, and can inhibit the interactions between the two proteins that can lead to immunosuppression, as exemplified by the human PD-L1/PD-1 interaction. By way of specific example, human PD-L1 and PD-1 polypeptides comprising glycosylated amino acid residues within their extracellular domains are provided for generating anti-glycosylated PD-L1 or anti-glycosylated PD-1 antibodies that specifically bind PD-L1 or PD-1, respectively, and inhibit the PD-L1/PD-1 interaction. The antibodies produced and selected by the methods are especially useful as cancer therapeutics for disrupting, blocking, or neutralizing the ICP system and specific ICP interactions therein.
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CRYSTALLINE FORMS OF 2-[(2S)-1-AZABICYCLO[2.2.2]OCT-2-YL]-6-(3-METHYL-1H- PYRAZOL-4-YL)THIENO[3,2-D]PYRIMIDIN-4(3H)-ONE HEMIHYDRATE (Fri, 06 Oct 2017)
The present disclosure relates to crystalline forms of 2-[(2S)-1-azabicyclo[2.2.2]oct-2-yl]-6-(3-methyl-1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-4(3H)-one hemihydrate (Compound 1) and/or tautomers thereof, wherein Compound 1 has the structure: (I) ⋅ 0.5 H2O; processes for preparing crystalline forms of Compound 1 and/or tautomers thereof; pharmaceutical compositions comprising the crystalline forms; methods of inhibiting a cell division cycle 7 in a mammal comprising administering the crystalline forms; and methods of treating a cell division cycle 7 mediated cancer in a mammal comprising administering the crystalline forms or a pharmaceutical composition comprising the crystalline forms.
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PYRROLOTRIAZINE COMPOUNDS AS TAM INHIBITORS (Fri, 06 Oct 2017)
This application relates to compounds of Formula I, or pharmaceutically acceptable salts thereof, which are inhibitors of TAM kinases which are useful for the treatment of disorders such as cancer.
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ESTROGEN RECEPTOR MODULATORS (Fri, 06 Oct 2017)
Compounds of Formula (I) are estrogen receptor alpha modulators, where the variables in Formula (I) are described in the disclosure. Such compounds, as well as pharmaceutically acceptable salts and compositions thereof, are useful for treating diseases or conditions that are estrogen receptor alpha dependent and/or estrogen receptor alpha mediated, including conditions characterized by excessive cellular proliferation, such as breast cancer.
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NOVEL COMPOSITIONS AND THERAPEUTIC METHODS (Fri, 06 Oct 2017)
The present invention is directed to novel products, variants, pharmaceutically acceptable salts and prodrugs thereof, and medical use of such compounds for the treatment and/or management of sepsis, septicemia, septic shock, ocular infection, ocular inflammation, ocular angiogenesis, rheumatoid arthritis (RA), atherosclerosis, inflammatory bowel diseases (IBD), asthma, chronic obstructive pulmonary disease, fever syndromes, cachexia, psoriasis, autoimmune diseases, cardiac diseases, retinoblastoma, cancer and/or any disorder associated with inflammation, immunomodulation and microbial infection.
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ISOQUINOLINYL TRIAZOLONE COMPLEXES (Fri, 06 Oct 2017)
Disclosed is a complex of a compound of Formula 1, a stereoisomer thereof, or a tautomer of the compound of Formula 1 or stereoisomer thereof, and a cyclodextrin, in which the complex is an amorphous solid. This disclosure also relates to materials and methods for preparing the complex, to pharmaceutical compositions which contain the complex, and to the use of the complex to treat Type I hypersensitivity reactions, autoimmune diseases, inflammatory disorders, cancer, non-malignant proliferative disorders, and other conditions associated with BTK.
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MAGNETIC NANOPARTICLE-POLYMER COMPLEXES AND USES THEREOF (Fri, 06 Oct 2017)
The present invention relates to magnetic nanoparticles coated with block copolymers. The invention further relates to methods of increasing cellular uptake of magnetic nanoparticles and use of the coated magnetic particles to selectively kill cancer cells, treat cancer, detect cancer, and for biomedical imaging.
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BCMA BINDING MOLECULES AND METHODS OF USE THEREOF (Fri, 06 Oct 2017)
The invention provides antibodies, antigen binding fragments thereof, chimeric antigen receptors (CARs), and engineered T cell receptors, polynucleotides encoding the same, and in vitro cells comprising the same. The polynucleotides, polypeptides, and in vitro cells described herein can be used in an engineered CAR T cell therapy for the treatment of a patient suffering from a cancer. In one embodiment, the polynucleotides, polypeptides, and in vitro cells described herein can be used for the treatment of multiple myeloma.
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PURINE INHIBITORS OF HUMAN PHOSPHATIDYLINOSITOL 3-KINASE DELTA (Fri, 06 Oct 2017)
The instant invention provides compounds of formula (I) which are PI3K-delta inhibitors, and as such are useful for the treatment of PI3K-delta-mediated diseases such as inflamation, asthma, COPD and cancer.
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COMBINED CANCER THERAPY WITH IMMUNE CHECKPOINT MODULATORS AND FERMENTATION PRODUCTS BY SYMBIOTIC MICROBIOTA (Fri, 06 Oct 2017)
Combined therapy of cancer using an immune checkpoint modulator (e.g., an immune checkpoint inhibitor) and a fermented product prepared by symbiotic microbiota.
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N1-(3,3,3-TRIFLUORO-2-HYDROXY-2-METHYLPROPIONYL)-PIPERIDINE DERIVATIVES AS INHIBITORS OF PYRUVATE DEHYDROGENASE KINASE (Fri, 06 Oct 2017)
Compounds of the formula (I) in which X, Q, R1 and R2 have the meanings indicated in Claim 1, are inhibitors of pyruvate dehydrogenase kinase (PDHK), and can be employed, inter alia, for the treatment of diseases such as cancer.
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Syk inhibitors (Fri, 06 Oct 2017)
The present disclosure relates to compounds that are Syk inhibitors and to their use in the treatment of various disease states, including cancer and inflammatory conditions. In particular embodiments, the structure of the compounds is given by Formula I: wherein R1, R2, R3, and R4 are as described herein. The present disclosure further provides pharmaceutical compositions that include a compound of Formula I, or pharmaceutically acceptable salts or co-crystals thereof, and methods of using these compounds and compositions to treat conditions mediated by Syk. Formula I
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BICYCLIC COMPOUND (Thu, 05 Oct 2017)
Provided is a bicyclic compound having an acetyl-CoA carboxylase inhibitory action. A compound represented by the formula: wherein each symbol is as described in the DESCRIPTION, or a salt thereof has an acetyl-CoA carboxylase inhibitory action, is useful for the prophylaxis or treatment of cancer, inflammatory diseases and the like, and has superior efficacy.
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2-AMINOPYRIMIDINE COMPOUND AND PHARMACEUTICAL COMPOSITION AND USE THEREOF (Thu, 05 Oct 2017)
Disclosed are a 2-aminopyrimidine compound and pharmaceutical composition and use thereof. The structure of the 2-aminopyrimidine compound is as represented by formula I, in the formula, R 1 , R 2 , R 3 , R 4 , R 5 , X, Y, Z, W, (i) being as defined in the specification and the claims. Such compounds effectively inhibit the growth of a variety of tumor cells and have inhibitory effects on EGFR and IGF1R protease, and can be used for preparing antineoplastic drugs and overcome the tolerance induced by the existing drugs such as gefitinib, erlotinib and the like. The compound has selectivity for tumors, in particular the wild-type non-small cell lung cancer and have good pharmacokinetic characteristics.
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SUBSTITUTED BENZOAZEPINES AS TOLL-LIKE RECEPTOR MODULATORS (Thu, 05 Oct 2017)
Provided are compounds of formula (I) useful for modulation of signaling through the Toll-like receptors TLR7 and/or TLR8. The compounds have use in treating or preventing oral cancer.
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PYRROLOTRIAZINE COMPOUNDS AS TAM INHIBITORS (Fri, 29 Sep 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="32.34mm" wi="61.13mm" file="US20170275290A1-20170928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salts thereof, which are inhibitors of TAM kinases which are useful for the treatment of disorders such as cancer.</p>
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MODIFIED MITO-METFORMIN COMPOUNDS AND METHODS OF SYNTHESIS AND USE THEREOF (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The present invention provides mito-metformin compounds, pharmaceutical compositions thereof, and methods of using the mito-metformin compounds in the treatment of cancer.</p>
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METHODS FOR THE PREPARATION OF DIASTEREOMERICALLY PURE PHOSPHORAMIDATE PRODRUGS (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Methods for the preparation of diastereomerically pure phosphoramidate prodrugs of nucleosides, and intermediates useful for the preparation are provided. The nucleosides are useful for the treatment of hepatitis C and cancer.</p>
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GLYCOLIPIDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR USE IN THERAPY (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">A compound of Formula I: R1-L1-C(A)(A′)-CH<sub>2</sub>, -L2-R2 or a pharmaceutically acceptable salt thereof, for use in medicine, for example in the treatment of a disease or condition selected from the group comprising cancer, autistic spectrum disorders. Alzheimer's disease, Parkinson's disease, Huntingdon's disease, muscle wasting and viral infection, wherein: R1 is selected from a carbohydrate group or derivative thereof, hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; L1 is a linking group; L2 is a linking group; R2 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; A is selected from hydrogen and a C1-C6 alkyl group: A′ is selected from hydrogen, a C3-C6 alkyl group, and L3-R3; wherein L3 is a linking group; and R3 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; and wherein if A′ is not L3-R3, then R2 is a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group; and wherein if A′ is L3-R3, then one or both of R2 and R3 are a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group.</p>
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Malate salt of N-(4-phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclo-propane-1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide.</p>
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ASYMMETRIC BISAMINOQUINOLINES AND BISAMINOQUINOLINES WITH VARIED LINKERS AS AUTOPHAGY INHIBITORS FOR CANCER AND OTHER THERAPY (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The invention provides novel asymmetric and symmetric bisaminoquinolmes and related compounds, methods of treatment and syntheses. The novel compounds exhibit effective anticancer activity and are useful in the treatment of a variety of autophagy-related disorders.</p>
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BENZAZEPINE SULFONAMIDE COMPOUNDS (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">This invention relates to novel benzazepine sulfonamide compounds of the formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.78mm" wi="63.58mm" file="US20170275253A1-20170928-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 R<sup>4 </sup>or R<sup>5 </sup>is —SO<sub>2</sub>—NR<sup>7</sup>R<sup>8 </sup>and R<sup>1 </sup>to R<sup>8 </sup>and Y 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.</li> </ul> </li> </ul> </p>
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Compounds for the treatment of HPV-induced carcinoma (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">A compound of Formula 1</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.03mm" wi="39.54mm" file="US20170275263A1-20170928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein,</li> <li id="ul0002-0002" num="0000">X represents an alkyl, alkylene, alkenyl, alkenylene, alkynyl or alkynylene group,</li> <li id="ul0002-0003" num="0000">optionally having at least one substituent selected from the group of —OR<sup>1 </sup>and —NR<sup>1</sup>R<sup>2</sup>, or</li> <li id="ul0002-0004" num="0000">Y represents —OTBS, —OR<sup>1</sup>, —NR<sup>1</sup>R<sup>2</sup>;</li> <li id="ul0002-0005" num="0000">Z represents —OR<sup>3 </sup>or ═O; and</li> <li id="ul0002-0006" num="0000">R<sup>1</sup>, R<sup>2 </sup>and R<sup>3 </sup>each independently stand for H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterocyclyl,</li> <li id="ul0002-0007" num="0000">optionally in the form of enantiomers racemic mixtures, or pharmaceutically acceptable salts thereof, for use as a medicament, in particular for use in anti-viral cancer treatment in mammals and for use in treatment of benign or neoplastic genital Human Papilloma Virus associated diseases and for use in treatment of non-genital warts.</li> </ul> </li> </ul> </p>
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HISTONE DEMETHYLASE INHIBITORS (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Provided herein are substituted pyrazolylpyridine, pyrazolylpyridazine, and pyrazolylpyrimidine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.</p>
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N-PYRIDINYL ACETAMIDE DERIVATIVES AS INHIBITORS OF THE WNT SIGNALING PATHWAY (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Disclosed are compounds useful as inhibitors of the Wnt signalling pathway. Specifically, inhibitors of Porcupine (Porcn) are contemplated by the invention. In addition, the invention contemplates processes to prepare the compounds and uses of the compounds. The compounds of the invention may therefore be used in treating conditions mediated by the Wnt signalling pathway, for example, in treating cancer, sarcoma, melanoma, skin cancer, haematological tumors, lymphoma, carcinoma, and leukemia; or enhancing the effectiveness of an anti-cancer treatment.</p>
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SUBSTITUTED CYCLOALKENOPYRAZOLES AS BUB1 INHIBITORS FOR THE TREATMENT OF CANCER (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Compounds of formula (I), processes for their production and their use as Bub1 kinase inhibitors for the treatment of hyperproliferative diseases and/or disorders responsive to induction of cell death.</p>
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NOVEL CAPSAZEPINE ANALOGS FOR THE TREATMENT OF CANCER AND OTHER PROLIFERATIVE DISEASES (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The present disclosure relates generally to derivatives of capsazepine and methods of use thereof In some aspects, the present disclosure relates to using capsazepine derivatives to treat cancer or other hyperproliferative diseases. In some aspects of the present disclosure, the disclosure provides capsazepine derivatives which may be useful in the treatment of cancer. Such cancers that the compounds may be used to treating include but are not limited to breast, cervical, oral, head, neck, or prostate cancer. In some aspects, the compounds may be useful in treating a tumor by direct injection of the compound into the tumor, particularly an oral tumor. In other aspects, the compounds are administered systemically. The compounds of the present disclosure may also be used to treat the pain associated with a tumor for which it is being administered.</p>
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DRUG DELIVERY OF TEMOZOLOMIDE FOR SYSTEMIC BASED TREATMENT OF CANCER (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The present invention relates to methods of drug delivery for the treatment of a condition or disease, such as cancer. In one embodiment, the invention provides a method of preparing a multifunctional nanoconjugate of temozolomide (TMZ) by conjugating TMZ in its hydrazide form to a polymalic acid platform. In another embodiment, the polymalic acid platform is conjugated to a monoclonal antibody to transferrin receptor, a trileucine (LLL) moiety, and/or a polyethylene glycol (PEG) moiety. The present invention relates to methods of drug delivery for the treatment of a condition or disease, such as cancer. In one embodiment, the invention provides a method of preparing a multifunctional nanoconjugate of temozolomide (TMZ) by conjugating TMZ in its hydrazide form to a polymalic acid platform. In another embodiment, the polymalic acid platform is conjugated to a monoclonal antibody to transferrin receptor, a trileucine (LLL) moiety, and/or a polyethylene glycol (PEG) moiety.</p>
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TREATMENT OF CANCER USING TLR9 AGONIST WITH CHECKPOINT INHIBITORS (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The invention provides methods of inducing an immune response to cancer comprising co-administering to a cancer patient one or more TLR9 agonists and one or more checkpoint inhibitors. Preferably, the one or more TLR9 agonists are administered to the patient via intratumoral (i.t.) administration.</p>
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GENE DELIVERY SYSTEM USING POLYMER NETWORK (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Provided is a gene delivery including a polymer network formed by binding phenylboronic acid, sugar, and a low-molecular weight branched polymer. The gene delivery may be stably maintained in vivo and efficiently deliver a gene specifically to cancer cells, such that the gene delivery system may be usefully used as a gene delivery system for chemotherapy.</p>
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ANTI-TUMOR COMPOUND AND THE MEDICAL USE THEREOF (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The invention disclose a compound of formula (I), wherein, R<sub>1 </sub>is selected from —H or C1-C6 hydrocarbon group, —NH<sub>2</sub>, —OH, —O(CH<sub>2</sub>)<sub>n</sub>CH<sub>3 </sub>(n=0, 1 or 2), —N(CH<sub>3</sub>)<sub>2</sub>, or —CH<sub>2</sub>N(CH<sub>3</sub>)<sub>2</sub>, R<sub>2 </sub>is selected from an amino acid</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="14.99mm" wi="17.44mm" file="US20170273933A1-20170928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or an hydroxy acid</p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="13.04mm" wi="17.44mm" file="US20170273933A1-20170928-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005" num="0000">or —OH (R<sub>1</sub>, R<sub>2 </sub>are not —CH<sub>3 </sub>and —OH at the same time), wherein X, Y are</p> <p id="p-0006" num="0000"><chemistry id="CHEM-US-00003" num="00003"> <img id="EMI-C00003" he="205.06mm" wi="43.18mm" file="US20170273933A1-20170928-C00003.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0007" num="0000">—H, —CH<sub>3</sub>, —CH<sub>2</sub>OH, —CH(OH)CH<sub>3</sub>, —CH<sub>2</sub>SH, —CH(CH<sub>3</sub>)<sub>2</sub>, —CH<sub>2</sub>CH(CH<sub>3</sub>)<sub>2</sub>, —CH(CH<sub>3</sub>)CH<sub>2</sub>CH<sub>3</sub>, —CH<sub>2</sub>CH<sub>2</sub>SCH<sub>3</sub>, —CH<sub>2</sub>COOH, —CH<sub>2</sub>CONH<sub>2</sub>, —CH<sub>2</sub>CH<sub>2</sub>COOH, —CH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>NH<sub>2</sub>, or —CH<sub>2</sub>CH<sub>2</sub>CONH<sub>2</sub>, R<sub>3</sub>-R<sub>5 </sub>are H or C1-C6 hydrocarbon group. The compound has a low toxicity, can significantly inhibit the migration and invasion of tumor cells in vitro, and can inhibit tumor metastasis in vivo in mice at low concentration, while showing notable sensitizing effect on cytotoxic anti-tumor drugs such as Paclitaxel etc.</p> <p id="p-0008" num="0000"><chemistry id="CHEM-US-00004" num="00004"> <img id="EMI-C00004" he="27.86mm" wi="53.42mm" file="US20170273933A1-20170928-C00004.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Taxane Analogs for the Treatment of Brain Cancer (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Provided herein are compounds and methods for the treatment of brain cancer in a mammal, wherein the method comprises the administration to the mammal a compound that stabilizes tubulin dimers or microtubles at G2-M interface during mitosis but is not a substrate for MDR protein. In particular, the present application relates to the use of an orally effective abeo-taxane, alone or in combination with temozolomide or bevacizumab, for the treatment of brain cancer.</p>
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PHARMACEUTICAL COMPOUNDS AND USE OF SAME IN CANCER AND TAUOPATHIES (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Disclosed are compounds of formula (I)-(V): where the substituents are as provided herein. Further disclosed are methods of inhibiting tau aggregation, treating or ameliorating a tauopathy or cancer by administration of such a compound. Tau is a microtubule-binding protein that accumulates in a number of neurodegenerative disorders, including frontotemporal dementia and Alzheimer's disease (AD). The presence of abnormal tau correlates with neuron loss and memory deficits in patients with AD and other neurodegenerative disorders that involve tau accumulation.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="214.04mm" wi="73.41mm" file="US20170273963A1-20170928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PULSE DOSING REGIMEN AND METHODS OF TREATMENT (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">A novel dosing regimen for erlotinib or a pharmaceutically acceptable salt thereof is described herein. The dosing regimen demonstrates impressive control of central nervous system disease, which is better than that reported with standard dose erlotinib. The use of the novel dosing regimen for treating patients in need thereof, including for controlling formation of metastatic brain, leptomeninges, or CNS lesions in a patient with non-small cell lung cancer (NSCLC) that harbors epidermal growth factor receptor (EGFR) mutation with or without pre-existing brain metastases, is also described herein.</p>
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A METHOD AND COMPOSITION FOR TREATING BREAST CANCER (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The invention disclosed herein relates to the use of an extract of <i>Dodonaea viscosa </i>in breast cancer therapy, either alone or in combination with other breast cancer therapies.</p>
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THERAPEUTIC COMPOSITIONS AND USES THEREOF (Fri, 29 Sep 2017)
This invention provides pharmaceutical and cosmeceutical compositions, including anti-epithelial cancer compositions, containing glyceride compounds, and compositions comprising one or more of these compounds. Methods of preparing and using such compositions, in particular in the treatment or prevention of epithelial cancers, such as skin cancers, gastrointestinal cancers, and skin disorders, are also provided.
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PULSE DOSING REGIMEN AND METHODS FOR TREATMENT (Fri, 29 Sep 2017)
A novel dosing regimen for erlotinib or a pharmaceutically acceptable salt thereof is described herein. The dosing regimen demonstrates impressive control of central nervous system disease, which is better than that reported with standard dose erlotinib. The use of the novel dosing regimen for treating patients in need thereof, including for controlling formation of metastatic brain, leptomeninges, or CNS lesions in a patient with non-small cell lung cancer (NSCLC) that harbors epidermal growth factor receptor (EGFR) mutation with or without pre-existing brain metastases, is also described herein.
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CINNOLIN-4-AMINE COMPOUNDS AND THEIR USE IN TREATING CANCER (Fri, 29 Sep 2017)
This specification generally relates to compounds of Formula (I). And pharmaceutically acceptable salts thereof, where R1, R2 and R3 have any of the meanings defined herein. The specification also relates to the use of such compounds and salts thereof to treat or prevent ATM kinase mediated disease, including cancer. The specification further relates to crystalline forms of compounds of Formula (I) and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds and salts thereof; kits comprising such compounds and salts thereof; methods of manufacture of such compounds and salts thereof; intermediates useful in the manufacture of such compounds and salts thereof; and to methods of treating ATM kinase mediated disease, including cancer, using compounds of Formula (I) and salts thereof alone or in combination with other therapies.
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QUINOLINE-3-CARBOXAMIDE COMPOUNDS AND THEIR USE IN TREATING CANCER (Fri, 29 Sep 2017)
This specification generally relates to compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, where R1, R2, R3, R4 and R5 have any of the meanings defined herein. The specification also relates to the use of such compounds and salts thereof to treat or prevent ATM kinase mediated disease, including cancer. The specification further relates to crystalline forms of compounds of Formula (I) and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds and salts thereof; kits comprising such compounds and salts thereof; methods of manufacture of such compounds and salts thereof; intermediates useful in the manufacture of such compounds and salts thereof; and to methods of treating ATM kinase mediated disease, including cancer, using such compounds and salts thereof alone or in combination with other therapies.
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1H-BENZO[DE]ISOQUINOLINE-1,3(2H)-DIONES (Fri, 29 Sep 2017)
The present invention covers 1 /-/-benzo[c/e]isoquinoline-1,3(2/-/)-dione compounds of general formula (I) compounds of general formula (I) : in which R1, R2, R3, R4 and R5 are as defined according to claim 1 and methods of preparing said compounds, as well as their use for the treament of cancer.
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USE OF NUCLEOSOME-TRANSCRIPTION FACTOR COMPLEXES FOR CANCER DETECTION (Fri, 29 Sep 2017)
The invention relates to the use of tissue specific transcription factor-nucleosome adducts or transcription cofactor-nucleosome adducts as biomarkers in a biological fluid for the detection or diagnosis of a cancer in a subject. The invention further relates to using said tissue specific transcription factor or cofactor adducts to identify the site of development of a cancer in a subject.
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1,4,5-SUBSTITUTED 1,2,3-TRIAZOLE ANALOGUES AS ANTAGONISTS OF THE PREGNANE X RECEPTOR (Fri, 29 Sep 2017)
In an aspect, the invention relates to 1,4,5 -substituted 1,2,3-triazole and 1,2,4,5- substituted imidazoles, which are modulators the pregnane X receptor ("PXR"); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of modulating an adverse drug reaction in a mammal using the compounds and pharmaceutical compositions; methods of treatment of a disorder of uncontrolled cellular proliferation, such as a cancer, using the compounds and pharmaceutical compositions; methods of modulating pregnane X receptor activity in a mammal using the compounds and pharmaceutical compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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ELECTRON WITHDRAWING GROUP SUBSTITUTED AND MACROCYCLIC PGJ3 ANALOGS AND METHODS OF TREATMENT THEREOF (Fri, 29 Sep 2017)
In some aspects, the present disclosure provides compounds of the formula: wherein the variables are as defined herein. In some embodiments, the present disclosure provides macrocylic compounds and oligomers thereof of formula I. As described herein, these compounds may be used to treat cancer or other hyperproliferative diseases.
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USE OF BENZOFURAN LIGNANS TO INDUCE IL-25 EXPRESSION AND SUPPRESS MAMMARY TUMOR METASTASIS (Fri, 29 Sep 2017)
A method for suppressing tumor metastasis, in which an effective amount of a compound of formula (I) is administered to a subject in need thereof. Also disclosed is a method of treating cancer, in which an effective amount of a chemotherapy agent and an effective amount of a compound of formula (I) is administered to a subject in need thereof. Further disclosed are pharmaceutical compositions for suppressing tumor metastasis and for treating cancer, each of the compositions containing a compound of formula (I).
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SMALL MOLECULE INHIBITOR OF THE NUCLEAR TRANSLOCATION OF ANDROGEN RECEPTOR FOR THE TREATMENT OF CASTRATION-RESISTANT PROSTATE CANCER (Fri, 29 Sep 2017)
A compound, or a stereoisomer, pharmaceutically acceptable salt, or ester thereof, according to formula (III) or according to Table A, a pharmaceutical composition comprising said compound and at least one pharmaceutically acceptable additive, and a method for treating prostate cancer in a subject, comprising administering to the subject a therapeutically effective amount of said compound.
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Biomarkers and methods of treating PD-1 and PD-L1 related conditions (Fri, 29 Sep 2017)
Provided herein are biomarkers for the treatment of pathological conditions, such as cancer, and method of using PD-I/PD-LI pathway antagonists. In particular, provided are biomarkers for patient selection and prognosis in cancer, as well as methods of therapeutic treatment, articles of manufacture and methods for making them, diagnostic kits, methods of detection and methods of advertising related thereto.
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Diarylhydantoin compounds (Fri, 29 Sep 2017)
The present invention relates to diarylhydantoin compounds, including diarylthiohydantoins, and methods for synthesizing them and using them in the treatment of hormone refractory prostate cancer.
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PYRAZOL-3-ONES THAT ACTIVATE PRO-APOPTOTIC BAX (Fri, 29 Sep 2017)
This application features pyrazol-3-one compounds that activate pro-apoptotic BAX. Also featured are methods of using such compounds, e.g., for the treatment or prevention of diseases, disorders, and conditions associated with deregulated apoptosis of cells (e.g., insufficient apoptosis of diseased or damaged cells or essentially the absence of apoptosis of diseased or damaged cells). See Fig. 1A.
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Method of treating cancer and bone cancer pain (Fri, 29 Sep 2017)
This invention is directed to the treatment of cancer, particularly lung cancer, breast cancer, melanoma, renal cell carcinoma, thyroid cancer that has metastasized to the bone. The invention is also directed to a method for treating bone cancer pain in an individual in need of such treatment comprising administering to the individual an effective amount of a compound of Formula I.
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FLUORESCENT SILICA-BASED NANOPARTICLES (Thu, 28 Sep 2017)
The present invention provides a fluorescent silica-based nanoparticle that allows for precise detection, characterization, monitoring and treatment of a disease such as cancer. The nanoparticle has a range of diameters including between about 0.1 nm and about 100 nm, between about 0.5 nm and about 50 nm, between about 1 nm and about 25 nm, between about 1 nm and about 15 nm, or between about 1 nm and about 8 nm. The nanoparticle has a fluorescent compound positioned within the nanoparticle, and has greater brightness and fluorescent quantum yield than the free fluorescent compound. The nanoparticle also exhibits high biostability and biocompatibility. To facilitate efficient urinary excretion of the nanoparticle, it may be coated with an organic polymer, such as poly(ethylene glycol) (PEG). The small size of the nanoparticle, the silica base and the organic polymer coating minimizes the toxicity of the nanoparticle when administered in vivo. In order to target a specific cell type, the nanoparticle may further be conjugated to a ligand, which is capable of binding to a cellular component associated with the specific cell type, such as a tumor marker. In one embodiment, a therapeutic agent may be attached to the nanoparticle. To permit the nanoparticle to be detectable by not only optical fluorescence imaging, but also other imaging techniques, such as positron emission tomography (PET), single photon emission computed tomography (SPECT), computerized tomography (CT), bioluminescence imaging, and magnetic resonance imaging (MRI), radionuclides/radiometals or paramagnetic ions may be conjugated to the nanoparticle.
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BIGUANIDE COMPOUND AND USE THEREOF (Thu, 28 Sep 2017)
The present invention relates to a guanidine compound and a use thereof, and more specifically, to a guanidine derivative showing excellent effects of inhibiting cancer cell proliferation, cancer metastasis, and cancer recurrence; a preparation method thereof; and a pharmaceutical composition containing the same as an active ingredient. Compared to existing drugs, the guanidine derivative according to the present invention shows excellent effects of inhibiting cancer cell proliferation, cancer metastasis, and cancer recurrence even with small doses, and may thus be effectively used in preventing or treating various cancers such as uterine cancer, breast cancer, stomach cancer, brain cancer, rectal cancer, colorectal cancer, lung cancer, skin cancer, blood cancer, liver cancer, etc., inhibiting cancer cell proliferation and cancer metastasis.
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PSMA-BINDING AGENTS AND USES THEREOF (Thu, 28 Sep 2017)
Prostate-specific membrane antigen (PSMA) binding compounds having radioisotope substituents are described, as well as chemical precursors thereof. Compounds include pyridine containing compounds, compounds having phenylhydrazine structures, and acylated lysine compounds. The compounds allow ready incorporation of radionuclides for single photon emission computed tomography (SPECT) and positron emission tomography (PET) for imaging, for example, prostate cancer cells and angiogenesis.
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LIPIDATED IMMUNE RESPONSE MODIFIER COMPOUND AND ITS MEDICAL USE (Thu, 28 Sep 2017)
The compound N-(4-{[4-amino-2-butyl-1 H -imidazo[4,5- c ]quinolin-1-yl]oxy}butyl)octadecanamide is a useful drug compound for enhancing immune response and can be used, for example, as a vaccine adjuvant and a cancer treatment.
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NOVEL PEPTIDE COMPOUND, PRODUCTION METHOD THEREFOR, AND USE THEREOF (Thu, 28 Sep 2017)
A novel peptide compound, a production method thereof, and a use thereof are provided. The compound has an anticancer activity and, thus the compound can be used for the preventing or treating cancer.
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COMBINATIONS OF COPANLISIB (Fri, 22 Sep 2017)
The present invention relates to * combinations of : component A : one or more 2,3-dihydroimidazo[l,2-c]quinazoline compounds of general formula (Al) or (A2) as defined herein, or a physiologically acceptable salt, solvate, hydrate or stereoisomer thereof; component B : one or more IRAK4-inhibiting compounds of general formula (I) as defined herein, or a physiologically acceptable salt, solvate, hydrate or stereoisomer thereof; in which optionally some or all of the components are in the form of a pharmaceutical formulation which is ready for use to be administered simultaneously, concurrently, separately or sequentially. dependently of one another by the oral, intravenous, topical, local installations, intraperitoneal or nasal route; * use of such combinations for the preparation of a medicament for the treatment or prophylaxis of a cancer; and * a kit comprising such a combination.
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ANTI-MICA ANTIBODIES (Fri, 22 Sep 2017)
The present invention provides antigen-binding proteins capable of binding to human MICA polypeptides. The antigen-binding proteins have increased activity in the treatment of disorders characterized by MICA-expressing cells, particularly cancer.
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ANTI-CD39 ANTIBODIES (Fri, 22 Sep 2017)
The present invention relates to antigen-binding compounds that inhibit CD39. The invention also relates to cells producing such compounds; methods of making such compounds, and antibodies, fragments, variants, and derivatives thereof; pharmaceutical compositions comprising the same; methods of using the compounds to diagnose, treat or prevent diseases, e.g. cancer.
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ENHANCERS OF NOTCH SIGNALING AND THEIR USE IN THE TREATMENT OF CANCERS AND MALIGNANCIES MEDICABLE BY UPREGULATION OF NOTCH (Fri, 22 Sep 2017)
The present invention relates to the use for enhancing Notch signaling in an individual, of a compound showing the general formula (I) and/or a pharmaceutically acceptable salt or ester thereof, for the treatment of a disease selected from the group of dermatological disorders including atopic dermatitis, psoriasis, immune related disorders, cancer, squamous cell carcinoma, cutaneous and lung squamous cell carcinoma, head and neck cancer, non-melanoma skin cancer, basal cell carcinoma and actinic keratosis, neuroendocrine tumors, neuroendocrine small cell carcinoma and carcinoid tumors, thyroid carcinomas, muscular disorders muscular dystrophy and impaired regeneration capacity after injury; use in immunotherapy for cancer.
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4,6 DIHYDROPYRROLO [3,4-C] PYRAZOLE-5 (1H)-CARBONITRILE DERIVATES FOR TRATING CANCER (Fri, 22 Sep 2017)
The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs) and/ or desumoylating enzymes. In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 7 or ubiquitin specific peptidase 7 (USP7). The invention further relates to the use of DUB or desumoylating inhibitors in the treatment of cancer. Described herein are compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1a, R1b, R1c and R1d each independently represent hydrogen, optionally substituted C1-C6 alkyl or R1a and R1b together form an optionally substituted C3-C6 cycloalkyl ring, or R1c and R1d together form an optionally substituted C3-C6 cycloalkyl ring; A is a 5 membered nitrogen-containing aromatic ring and is substituted with at least one optionally substituted 5 to 10 membered monocyclic or bicyclic heteroaryl or aryl ring attached through an optional linker.
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2-CYANOISOINDOLINE DERIVATIVES FOR TREATING CANCER (Fri, 22 Sep 2017)
The invention relates to novel compounds of formula I which are inhibitors of deubiquitylating enzymes (DUBs) and/or desumoylating enzymes. In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 7 or ubiquitin specific peptidase 7 (USP7). The invention further relates to methods for the preparation of these compounds and to their use in the treatment of cancer.
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FUSION PROTEINS TARGETING TUMOUR ASSOCIATED MACROPHAGES FOR TREATING CANCER (Fri, 22 Sep 2017)
The present invention relates to cancer immunotherapy. In particular, provided herein are fusion proteins for targeting tumor associated macrophages with immunostimulatory agents.
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OLIGOLACTIC ACID CONJUGATES AND MICELLES WITH ENHANCED ANTICANCER EFFICACY (Fri, 22 Sep 2017)
The present technology relates generally to oligolactic acid conjugates of paclitaxel, rapamycin, selumetinib, and other anticancer agents, micelle compositions containing such conjugates and methods of preparing and using such compositions to treat various cancers. Specifically, there are provided oligolactic acid conjugates wherein the oligolactic acid comprises 2 to 24 lactic acid subunits and is attached through an ester linkage to the oxygen of the 7-hydroxyl of the paclitaxel or paclitaxel derivative, the 40-hydroxyl of the rapamycin or rapamycin derivative, and the 2'-hydroxyl of the selumetinib or selumetinib derivative. Compositions comprising water and a micelle comprising a polylactic acid-containing polymer and the oligolactic acid conjugate may be readily prepared. Methods of inhibiting or killing cancer cells and treating paclitaxel, rapamycin, and/or selumetinib cancers are also provided.
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NOVEL SELENAZOLIDINE AND THIAZOLIDINE COMPOUNDS FOR TREATING CANCER AND OTHER DISEASES (Fri, 22 Sep 2017)
The present invention includes compounds useful in preventing or treating cancer in a subject in need thereof. The present invention also includes methods of preventing or treating cancer in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention.
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INHIBITORS FOR SOLUBLE EPOXIDE HYDROLASE (SEH) AND FATTY ACID AMIDE HYDROLASE (FAAH) (Fri, 22 Sep 2017)
The present invention provides compounds that are dual inhibitors of soluble epoxide hydrolase and fatty acid amide hydrolase. The present invention also provides methods of using the compounds to inhibit soluble epoxide hydrolase and fatty acid amide hydrolase, and to treat cancer.
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KNOTTIN-DRUG CONJUGATES AND METHODS OF USING THE SAME (Fri, 22 Sep 2017)
Provided are knottin-drug conjugates. The conjugates include a knottin peptide that includes an engineered loop that binds to a target on a cancer cell surface, and a drug (e.g., a nucleoside drug) conjugated to the knottin peptide through a linker. Also provided are pharmaceutical compositions and kits that include the knottin-drug conjugates, as well as methods of using the knottin-drug conjugates, e.g., for therapeutic purposes.
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AZA-A-RING INDENOISOQUINOLINE TOPOISOMERASE I POISONS (Fri, 22 Sep 2017)
The invention described herein pertains to four series of aza-A-ring indenoisoquinolines, which are inhibitors of topoisomerase IB (Top1), and the processes for preparing said aza-A-ring indenoisoquinolines. Also described are methods for treating cancer in mammals using the described aza-A-ring indenoisoquinoline compounds or pharmaceutical formulations thereof.
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HISTONE DEMETHYLASE INHIBITORS (Fri, 22 Sep 2017)
The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted pyrido[3,4-d] pyrimidin-4-one derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, melanoma, and the like.
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NANOPARTICLE TO TARGET CANCER (Fri, 22 Sep 2017)
A construct, or a pharmaceutically acceptable salt thereof, comprising: (a) a polyethylene glycol-block-poly(L-lysine) polymer moiety, wherein the polyethylene glycol is thiol-functionalized; (b) a cholecystokinin-B (CCK-B) receptor ligand coupled to the polyethylene glycol of the polymer moiety; and (c) a siRNA complexed with the poly(L-lysine) of the polymer moiety, wherein the construct is neutralized.
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HISTONE DEMETHYLASE INHIBITORS (Fri, 22 Sep 2017)
The present invention relates generally to compositions and methods for treating cancer and neoplastic diseases. Provided herein are substituted imidazole-pyridine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of histone demethylase enzymes. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as pancreatic cancer, prostate cancer, breast cancer, bladder cancer, lung cancer, gastric cancer, leukemia and/or melanoma and the like.
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EPHRIN RECEPTOR A2 (EPHA2)-TARGETED DOCETAXEL-GENERATING NANO-LIPOSOME COMPOSITIONS (Fri, 22 Sep 2017)
EphA2-targeted immunoliposomes for delivering docetaxel are useful in the treatment of certain types of cancer. The immunoliposomes can include an EphA2 targeting moiety (e.g., a scFv) and encapsulate a docetaxel prodrug in a stable salt form within a liposome having an average size of about 100 nm. Novel docetaxel prodrugs suitable for loading into nanoliposomes (including immunoliposomes) are provided, along with novel and other useful EphA2 targeting moieties for preparation of EphA2-targeted doxorubicin-generating immunoliposome therapies. Pharmaceutical compositions can be prepared that include nanoliposomes encapsulating one or more docetaxel prodrugs, and/or immunoliposomes or nanoparticles comprising an EphA2 binding moiety and encapsulating one or more docetaxel prodrugs. The pharmaceutical compositions are useful for administration to a patient for the treatment of cancer.
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TREATING EPHRIN RECEPTOR A2 (EPHA2) POSITIVE CANCER WITH TARGETED DOCETAXEL-GENERATING NANO-LIPOSOME COMPOSITIONS (Fri, 22 Sep 2017)
EphA2 targeted doxorubicin generating nano-liposomes are useful in the treatment of cancer overexpressing EphA2, alone or in combination with chemotherapeutic agents such as gemcitabine or carboplatin.
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ANTIBODY MIMIC CONJUGATES AND PARTICLES (Fri, 22 Sep 2017)
Particles, including nanoparticles and microparticles, and pharmaceutical formulations thereof, comprising conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to a targeting moiety via a linker have been designed which can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or infectious diseases.
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SMALL MOLECULES AGAINST CEREBLON TO ENHANCE EFFECTOR T CELL FUNCTION (Fri, 22 Sep 2017)
Disclosed are small molecules against cereblon to enhance effector T cell function. Methodos of making thes molecules and methods of using them to treat various disease states are also disclosed.
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CARBONIC ANHYDRASE IX INHIBITOR CONJUGATES AND USES THEREOF (Fri, 22 Sep 2017)
The present disclosure relates to compositions and methods of carbonic anhydrase IX inhibitors. The present disclosure also relates to targeting conjugates of carbonic anhydrase IX inhibitors as therapeutics and imaging agents. The present disclosure also relates to the use of targeting conjugates of carbonic anhydrase IX inhibitors in imaging methods and cancer therapy.
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INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE (Fri, 15 Sep 2017)
The invention relates to a compound of Formula (I), or pharmaceutically acceptable enantiomers, or salts thereof. The present invention also relates to the use of compounds of Formula (I) as selective inhibitors of indoleamine 2,3-dioxygenase. The invention also relates to the use of the compounds of Formula (I) for the treatment or prevention of diseases cancer, infections, central nervous system disease or disorder, and immune-related disorders, either as a single agent or in combination with other therapies.
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TOTAL CELLULAR IRON AS A MARKER OF CANCER STEM CELLS AND USES THEREOF (Fri, 15 Sep 2017)
The present invention relates to a novel use of total cellular iron, preferably under the form of ferrous iron (Fe2+), as a marker of cancer stem cells (CSCs). The invention also relates to methods using said iron marker, in particular for metastatic cancer diagnosis or treatment, for screening for compounds of interest, as well as for killing CSCs.
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3-OXA-8-AZABICYCLO[3.2.1]OCTANE DERIVATIVES AND THIER USE IN THE TREATMENT OF CANCER AND HEMOGLOBINOPATHIES (Fri, 15 Sep 2017)
A compound of formula Ia, Ib, Ic or Id: wherein: n is 1 or 2;R N is H or Me; R1 is optionally one or more halo or methyl groups;R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H;(iii) Me; and (iv) CH2 OH; R 2c and R 2d (if present) are independently selected from the group consisting of: (i) F; (ii) H;(iii) Me; and(iv) CH 2 OH;R 3a and R 3b are independently selected from H and Me; R 4a is selected from OH,-NH 2, -C(=O)NH 2, and -CH 2 OH; R 4b is either H or Me; R5 is either H or Me; m is 1 or 2; q is 0 or 1;R 11a, R 11b, R 11c and R 11d are independently selected from H, halo, C1-4 alkyl, C 1-4 fluoroalkyl, C 3-4 cycloalkyl, C 1-4 alkyloxy, NH-C 1-4 alkyl and cyano; R 12a and R 12b are independently selected from the group consisting of: (i) F; (ii) H;(iii) Me; and (iv) CH 2 OH; R 12c and R 12d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH 2 OH;R 12e is H or Me; R 13a and R 13b are independently selected from H and Me; R 14 is either H or Me; R 16a and R 16b are independently selected from H and Me; R 6 is selected from H, OMe, and OEt.
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BENZOPIPERIDINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF CANCER AND HEMOGLOBINOPATHIES (Fri, 15 Sep 2017)
A compound of formula I: (I) wherein: n is 1 or 2; p is 0 or 1; R1a, R1b, R1c and R1d are independently selected from H, halo, C1-4 alkyl, C1-4 fluoroalkyl, C3-4 cycloalkyl, C1-4 alkyloxy, NH-C1-4 alkyl and cyano; R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2c and R2d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2e is H or Me; R3a and R3b are independently selected from H and Me; R4 is either H or Me; R5 is either H or Me; R6a and R6b are independently selected from H and Me; A is either (IIa), where R7a is selected from N-linked N-containing C5-7 heterocycyl and (A); or (ii) (IIb), where X is selected from CH2, N H and O, one of R8a and R8b is selected from CI and ethoxy and the other of R8a and R8b is H.
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PYRIDINE DERIVATIVES AND THIER USE IN THE TREATMENT OF CANCER AND HEMOGLOBINOPATHIES (Fri, 15 Sep 2017)
A compound of formula (Ia), (Ib) or (Ic) wherein: n is 1 or 2; RN is H or Me; R1 is optionally one or more halo or methyl groups; R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2c and R2d (if present) are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R3a and R3b are independently selected from H and Me; R4a is selected from OH, -NH2, -C(=O)NH2, and -CH2OH; R4b is either H or Me; R5 is either H or Me; A is either (i), where R6a is ether; or (ii),, where X is selected from CH2, NH and O, one of R7a and R7b is selected from CI and ethoxy and the other of R7a and R7b is H.
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IMIDAZO[4,5-C]QUINOLIN-2-ONE COMPOUNDS AND THEIR USE IN TREATING CANCER (Fri, 15 Sep 2017)
The specification generally relates to compounds of Formula (I): and pharmaceutically acceptable salts thereof, where R1 is tetrahydropyran-3-yl or 3,3-dimethyltetrahydropyran-4-yl; R2 is methyl or hydro; R3 is hydro or fluoro; R4 is hydro or fluoro; and R5 is methyl or hydro; the use of compounds of Formula (I) or pharmaceutically acceptable salts thereof to treat or prevent ATM mediated disease, including cancer; pharmaceutical compositions comprising substituted imidazo [4,5- c]quinolin-2-one compounds or pharmaceutically acceptable salts thereof; kits comprising compounds of Formula (I) or pharmaceutically acceptable salts thereof; methods of manufacture of compounds of Formula (I) or pharmaceutically acceptable salts thereof; and intermediates useful in such manufacture.
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BENZO[B]THIOPHENE DERIVATIVES AND THEIR USE FOR THE INHIBITION OF FIBROBLAST GROWTH FACTOR RECEPTOR KINASES (FGFRS) FOR THE USE OF NEO- AND HYPERPLASIA THERAPIES (Fri, 15 Sep 2017)
The present invention relates to benzo[b]thiophene derivatives of general formula (I) and pharmaceutically acceptable salts, solvates, hydrates, stereoisomeric and polymorphic forms thereof wherein R1 is selected from the group of hydrogen; hydroxyl; substituted or unsubstituted heterocyclyl; optionally substituted amino; X, Y and Z are selected independently from the followings: CH (methine), nitrogen; R2, R3, R4 and R5 may stand for e.g. hydrogen, halogen, hydroxyl, alkyl, alkenyl, alkynyl, alkoxy and amino. The invention also relates to the use of them as of medication, as well as pharmaceutical compositions containing at least one of them as pharmaceutically active agent(s) together with pharmaceutically acceptable carrier, excipient and/or diluent, especially for the inhibition Fibroblast Growth Factor Receptor kinases (FGFR's), e.g. for the treatment of cancer.
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5-SULFAMOYL-2-HYDROXYBENZAMIDE DERIVATIVES (Fri, 15 Sep 2017)
The invention is directed to substituted salicylamide derivatives. Specifically, the invention is directed to compounds according to Formula (I): wherein R, R1 and R2 are as defined herein, or a pharmaceutically acceptable salt thereof. The compounds of the invention are inhibitors of CD73 and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with CD73 inhibition, such as AIDS, the treatment of HIV, autoimmune diseases, infections, atherosclerosis, and ischemia–reperfusion injury. 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 CD73 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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4BETA-AMIDOTRIAZOLE LINKED PODOPHYLLOTOXIN DERIVATIVES AS POTENTIAL ANTICANCER AGENTS (Fri, 15 Sep 2017)
The present invention relates to a compound of general formula (A). The invention provides asynthesis of new 4β-amidotriazole linked podophyllotoxin derivatives of general formulae 8a-z to 9a-z useful as potential anticancer agents against human cancer cell lines and process for the preparation thereof. Wherein n = 0,1 and R1-R5 = [H, CI, F, CH3, OCH3, 3,4(-OCH2O-), CF3, OCF3, m-OC6H5, OH]
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METHODS OF DIAGNOSING CANCER (Fri, 15 Sep 2017)
Disclosed are two methods of treating or preventing a proliferative disease as characterized and/or diagnosed by at least one selected from an accumulation of branched-chain amino acid (s) (BCAA), suppression of activity or transcripts level of BCAA catabolic enzyme(s) and a decrease in acylcarnitine level (C5:1 ), one comprising the administration of a BCAA catabolism enhancer and/or branched chain alpha-ketoacid dehydrogenase complex (BCKDC) kinase inhibitor and the other comprising administration of a meal replacement with low BCAA levels. In three separate embodiments, methods of diagnosis or prognosis are disclosed, each comprising the measurement of the levels of a different marker, i.e. BCAA, BCAA catabolic enzymes or acylcarnitine (C5:1 ). In preferred embodiments, the proliferative disease is cancer. Also disclosed is a kit or microarray chip useful for methods thereof.
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NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO (Fri, 15 Sep 2017)
This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.
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SUBSTITUTED HETEROCYCLES AS C-MYC TARGETING AGENTS (Fri, 15 Sep 2017)
Disclosed are substituted heterocycles compounds including substituted pyrazoles, substituted pyrimidines, and substitute triazoles. The substituted heterocycles disclosed herein are shown to be useful in inhibiting c-MYC and may be utilized as therapeutics for treating cancer and cell proliferative disorders.
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SMALL MOLECULE INDUCERS OF REACTIVE OXYGEN SPECIES AND INHIBITORS OF MITOCHONDRIAL ACTIVITY (Fri, 15 Sep 2017)
This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a quinazolinedione structure which function as reactive oxygen species (ROS) inducers and inhibitors of mitochondrial activity within cancer cells (e.g., pancreatic cancer cells), and their use as therapeutics for the treatment of cancer (e.g., pancreatic cancer) and other diseases.
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CYCLIC KETO-AMIDE COMPOUNDS AS CALPAIN MODULATORS AND METHODS OF PRODUCTION AND USE THEREOF (Fri, 15 Sep 2017)
The present technology relates to cyclic keto-amide compounds of general formulae I to XXXII, compositions and kits thereof as calpain modulators and methods useful for the treatment of various diseases or disorders such as fibrotic disease or cancer which are associated or mediated, by calpains, such as CAPN1, CAPN2, and/or CAPN9. The present technology is also applicable to cyclic keto-amide compounds which inhibit myofibroblast differentiation.
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HYPERPOLARIZED MICRO-NMR SYSTEM AND METHODS (Fri, 15 Sep 2017)
Described herein are micro-coil hyperpolarized NMR systems and methods for measuring metabolic flux in living and non-living samples. Such systems can perform high throughput measurements (with multiple coils) of metabolic flux without destroying the material, making it useful to analyze tumor biopsies, cancer stem cells, and the like. In certain embodiments, a hyperpolarized micromagnetic resonance spectrometer (HMRS), described herein, is used to achieve real-time, significantly more sensitive (e.g., 103-fold more sensitive) metabolic analyses of live cells or non-living samples. In this platform, a suspension mixed with hyperpolarized metabolites is loaded into a miniaturized detection coil (e.g., about 2 μL), where the flux analysis can be completed within a minute without significant changes in viability. The sensitive and rapid analytical capability of the provided systems enables rapid assessment of metabolic changes by a given drug, which may direct therapeutic choices in patients.
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CAMPTOTHECIN DERIVATIVES AND USES THEREOF (Fri, 15 Sep 2017)
Provided herein are camptothecin derivatives and pharmaceutical compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, cancer using the compounds and pharmaceutical compositions disclosed herein.
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COMPOSITE NANOPARTICLES AND USES THEREOF (Fri, 15 Sep 2017)
Provided herein are composite nanoparticles, methods of making composite nanoparticles and methods of using composite nanoparticles to treat or ameliorate various diseases, such as, for example, cancer.
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HETEROCYCLIC INHIBITORS OF PTPN11 (Fri, 15 Sep 2017)
The present invention relates to compounds which may be useful as inhibitors of PTPN11 for the treatment or prevention of cancer and other PTP-mediated diseases. The compounds are based on various substituted ring-fused pyrimidin-4-ones.
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ANTI-CANCER AND SPLCE MODULATING COMPOUNDS AND METHODS (Fri, 15 Sep 2017)
There are provided inter alia stable anti-cancer compounds and splice modulators and methods of synthesis and use thereof.
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INHIBITORS OF CREB-CBP INTERACTION FOR TREATMENT OF LEUKEMIA (Fri, 15 Sep 2017)
Compounds and methods are provided for inhibiting a CREB-CBP protein-protein interaction in a sample. In some cases, the method includes modulating transcription of CREB in a cell that overexpresses CREB. Also provided are methods of inhibiting the proliferation of a cancer cell. The subject CREB transcription inhibitor compounds include a substituted salicylamide or a prodrug thereof. Methods of alleviating symptoms associated with cancer (e.g., Acute Myeloid Leukemia (AML) or Acute Lymphomblastic Leukemia (ALL)) in a subject in need thereof are also provided. Pharmaceutical compositions including the subject compounds find use in treating cancer. The subject compounds may be formulated or provided to a subject in combination with a second agent, e.g. an anticancer agent.
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AURORA KINASE AND JANUS KINASE INHIBITORS FOR PREVENTION OF GRAFT VERSUS HOST DISEASE (Fri, 15 Sep 2017)
Disclosed herein are compounds and methods for reducing the risk of developing, preventing, or treating graft versus host disease (GVHD) in a subject. The compounds can concurrently block Aurora kinase A and JAK2 signal transduction which synergistically suppresses alloreactive human T-cells in vitro, prevents xenogeneic graft- versus-host disease without impairing anti-tumor responses, and promotes the development and suppressive potency of CD39+ inducible Treg. In certain aspects, disclosed are compounds of Formula I-V.
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BICYCLIC UREA, THIOUREA, GUANIDINE AND CYANOGUANIDINE COMPOUNDS USEFUL FOR THE TREATMENT OF PAIN (Fri, 15 Sep 2017)
[0010131 Compounds of Formula I: or stereoisomers, tautomers, or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein Ring A, Ring C and X are as defined herein, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis and pelvic pain syndrome.
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Bromodomain inhibitors (Fri, 15 Sep 2017)
2 3 4 1 2 The present invention provides for compounds of formula (I) wherein A1 , A , A , A , X , X , Y L', G1 , R', and R1 have any of the values defined thereof in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).
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INHIBITORS OF WDR5 PROTEIN-PROTEIN BINDING (Sat, 09 Sep 2017)
The present application is directed to compounds of Formula I: compounds comprising these compounds and their uses, for example as medicaments for the treatment of diseases, disorders or conditions mediated or treatable by inhibition of binding between WDR5 protein and its binding partners.
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INHIBITORS OF WDR5 PROTEIN-PROTEIN BINDING (Sat, 09 Sep 2017)
The present application is directed to compounds of Formula I: (I) compositions comprising these compounds and their uses, for example as medicaments for the treatment of diseases, disorders or conditions mediated or treatable by inhibition of binding between WDR5 protein and its binding partners.
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1-(PYRIMIDIN-2-YL)-1H-INDAZOLES HAVING BUB1 KINASE INHIBITING ACTIVITY (Sat, 09 Sep 2017)
The present invention relates to Bub1 kinase (= Budding uninhibited by benzimidazole kinase) inhibiting 1-(pyrimidin-2-yl)-1H-indazole compounds of formula (I), i.e. which therefore have potential to treat hyperprofilerative diseases such as cancer.
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SPIRO-CONDENSED PYRROLIDINE DERIVATIVES AS DEUBIQUITYLATING ENZYMES (DUB) INHIBITORS (Sat, 09 Sep 2017)
The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of Cezanne 1. The invention further relates to the use of DUB inhibitors in the treatment of cancer. (Figure (I))
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ANTIBODIES TO CD40 WITH ENHANCED AGONIST ACTIVITY (Sat, 09 Sep 2017)
Provided herein are agonistic antibodies, or antigen binding portions thereof, that bind to human CD40. Such antibodies optionally comprise Fc regions with enhanced specificity for FcϒRIIb. The invention also provides methods of treatment of cancer or chronic infection by administering the antibodies of the invention to a subject in need thereof.
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HSP90 INHIBITOR DRUG CONJUGATES (Sat, 09 Sep 2017)
The present invention provides Hsp90 drug conjugates (HDCs) comprising an Hsp90 ligand or prodrug thereof, a linker moiety and a payload moiety. The invention also provides methods for treating a disease or disorder in a subject, for example cancer, with an HDC.
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THERAPEUTIC AND DIAGNOSTIC METHODS FOR CANCER (Sat, 09 Sep 2017)
The present invention provides therapeutic and diagnostic methods and compositions for cancer, for example, bladder cancer. The invention provides methods of treating bladder cancer, methods of determining whether a patient suffering from bladder cancer is likely to respond to treatment comprising a PD-L1 axis binding antagonist, methods of predicting responsiveness of a patient suffering from bladder cancer to treatment comprising a PD-L1 axis binding antagonist, and methods of selecting a therapy for a patient suffering from bladder cancer, based on somatic mutation levels of genes of the invention (e.g., somatic mutation levels in a tumor sample obtained from the patient).
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STAPLED INTRACELLULAR-TARGETING ANTIMICROBIAL PEPTIDES TO TREAT INFECTION (Sat, 09 Sep 2017)
Structurally stabilized, e.g., stapled, peptides with the ability to translocate through microbial cell membranes to the interior of microbial cells and exert a biological activity there are provided, as are methods of designing, making and using such peptides.
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4,9-DIOXO-4,9-DIHYDRONAPHTHO(2,3-B)FURAN-3-CARBOXMIDE DERIVATIVES AND USES THEREOF FOR TREATING PROLIFERATIVE DISEASES AND INFECTIOUS DISEASES (Sat, 09 Sep 2017)
The present disclosure provides compounds of Formulas (I), (II), and pharmaceutically acceptable salts thereof. The compounds described herein are useful in treating proliferative diseases, for example, cancer (e.g., lung cancer), and infectious diseases (e.g., bacterial infections).
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ENHANCED CANCER IMMUNOTHERAPY BY MICRONEEDLE PATCH-ASSISTED DELIVERY (Sat, 09 Sep 2017)
Disclosed herein are self-degradable microneedle devices for the controlled-release of an immunotherapeutic agent. Also disclosed are methods for treating a disease (for example, cancer) using a self-degradable microneedle patch for the sustained delivery of an immunotherapeutic agent (for example, a PD1 antibody).
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IMMUNOMODULATORS (Sat, 09 Sep 2017)
The present disclosure provides novel macrocyclic compounds which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.
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STING ACTIVATING NANOVACCINE FOR IMMUNOTHERAPY (Sat, 09 Sep 2017)
In some aspects, the present disclosure provides vaccine compositions comprising an antigen and a diblock copolymer wherein the diblock copolymer is pH responsive. In some embodiments, these compositions activate the STING and/or the interferon receptor pathways. In some embodiments, the diblock copolymer has a pKa from about 6 to about 7.5. Also provided herein are methods of treatment using these compositions to treat an infectious disease or cancer.
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ERIBULIN-BASED ANTIBODY-DRUG CONJUGATES AND METHODS OF USE (Sat, 09 Sep 2017)
Linker toxins and antibody-drug conjugates that bind to human oncology antigen targets such as folate receptor alpha and/or provide anti-tubulin drug activity are disclosed. The linker toxins and antibody-drug conjugates comprise an eribulin drug moiety and can be internalized into target antigen-expressing cells. The disclosure further relates to methods and compositions for use in the treatment of cancer by administering the antibody-drug conjugates provided herein.
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NOVEL OXAZOLE AND THIAZOLE COMPOUNDS AS Β-CATENIN MODULATORS AND USES THEREOF (Sat, 09 Sep 2017)
Heterocyclic compounds according to formula I: wherein A, B, Y, and Cy are as described herein, are provided as inhibitors of the Wnt pathway that specifically target the activity of the stabilized pool of B-cat. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, cancer, and other conditions related to Wnt pathway dysfunction, including various cancers and pulmonary fibrosis.
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SUBSTITUTED INDOLE MCL-1 INHIBITORS (Sat, 09 Sep 2017)
The present disclosure provides for compounds that inhibit the activity of an anti- apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present disclosure also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over- expression or dysregulation of Mcl-1 protein.
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VIRUS VECTORS EXPRESSING MULTIPLE EPITOPES OF TUMOR ASSOCIATED ANTIGENS FOR INDUCING ANTITUMOR IMMUNITY (Sat, 09 Sep 2017)
Provided are polynucleotides and viral vectors, particularly, alphavirus vectors such as Sindbis viral vectors, which encode multiple, e.g., two or more, epitopes of at least one tumor associated antigen in which each epitope is separated by a processing or enzyme cleavage site. The multiple epitopes of the two or more tumor associated antigens encoded by the described polynucleotides and viral vectors may be the same or different. Methods of treating mammalian subjects having a cancer or tumor expressing the tumor associated antigen epitopes are provided, in which the viral vectors encoding the multiple epitopes, as well as other immunostimulatory or immunomodulatory components, generate an anti-cancer or anti-tumor immune response in which high levels of effector T cells increase the survivability of tumored mammalian subjects and result in epitope spreading, thus providing a further enhancement of the immune response.
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ARYL-OR HETEROARYL-SUBSTITUTED BENZENE COMPOUNDS (Fri, 08 Sep 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>
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IMMUNOMODULATORS (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present disclosure provides novel macrocyclic compounds which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.</p>
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ERIBULIN-BASED ANTIBODY-DRUG CONJUGATES AND METHODS OF USE (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">Linker toxins and antibody-drug conjugates that bind to human oncology antigen targets such as folate receptor alpha and/or provide anti-tubulin drug activity are disclosed. The linker toxins and antibody-drug conjugates comprise an eribulin drug moiety and can be internalized into target antigen-expressing cells. The disclosure further relates to methods and compositions for use in the treatment of cancer by administering the antibody-drug conjugates provided herein.</p>
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4-OXO-N-(4-HYDROXYPHENYL)RETINAMIDE DERIVATIVES AS THERAPEUTIC AGENTS FOR THE TREATMENT OF CANCER (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present invention relates to a compound having formula (I) below or a pharmaceutically acceptable salt thereof:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="43.52mm" wi="73.15mm" file="US20170253560A1-20170907-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein:</p> <p id="p-0004" num="0000">X is —COOH or NH<sub>2</sub>;</p> <p id="p-0005" num="0000">R is a straight or branched C<sub>1</sub>-C<sub>10 </sub>alkylene chain; and</p> <p id="p-0006" num="0000">R<sub>1 </sub>is H, straight or branched C<sub>1</sub>-C<sub>10 </sub>alkyl, aryl, or R<sub>2</sub>CO— wherein R<sub>2 </sub>is straight or branched C<sub>1</sub>-C<sub>10 </sub>alkyl, for use as antitumoral agents.</p>
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SUBSTITUTED HETEROCYCLES AS c-MYC TARGETING AGENTS (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">Disclosed are substituted heterocycles compounds including substituted pyrazoles, substituted pyrimidines, and substitute triazoles. The substituted heterocycles disclosed herein are shown to be useful in inhibiting c-MYC and may be utilized as therapeutics for treating cancer and cell proliferative disorders.</p>
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PYRIMIDINE COMPOUNDS AND PYRIMIDO INDOLE COMPOUNDS AND METHODS OF USE (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present invention discloses a compound comprising the formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.89mm" wi="53.51mm" file="US20170253612A1-20170907-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R is hydrogen or an alkyl group having from one to ten carbon atoms, or a compound of the formula wherein the S is replaced by CH<sub>2</sub>, and optionally comprising a pharmaceutically acceptable salt, hydrate, or solvate thereof. A method of treating a patient having cancer or a disease comprising administering to a patient an effective amount of the compound or pharmaceutically acceptable salt, hydrate, or solvate thereof.</p>
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ANTIBODIES TO CD40 WITH ENHANCED AGONIST ACTIVITY (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">Provided herein are agonistic antibodies, or antigen binding portions thereof, that bind to human CD40. Such antibodies optionally comprise Fc regions with enhanced specificity for FcγRIIb. The invention also provides methods of treatment of cancer or chronic infection by administering the antibodies of the invention to a subject in need thereof.</p>
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TRIAZOLE MODIFIED COUMARIN AND BIPHENYL AMIDE-BASED HSP90 INHIBITORS (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">Provided herein are compounds of the formulas: which are 90-kDa heat shock protein inhibitors. Pharmaceutical compositions of the compounds are also provided. In some aspects, these compounds may be used for the treatment of diseases, including cancer, e.g., cancers of the breast, the prostate, and the head & neck.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="77.22mm" wi="66.97mm" file="US20170253582A1-20170907-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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HETEROAROMATIC CHALCONE DERIVATIVES AND THEIR MEDICAL USE (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present invention relates to heteroaromatic chalcone derivatives, particularly the compounds of formula (I) as described and defined herein, pharmaceutical compositions comprising these compounds, and their medical use, including their use in the treatment or prevention of cancer and, in particular, in the treatment or prevention of hematologic malignancies.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.28mm" wi="61.89mm" file="US20170253583A1-20170907-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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BICYCLIC AROMATIC CARBOXAMIDE COMPOUNDS USEFUL AS PIM KINASE INHIBITORS (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present disclosure describes bicyclic aromatic carboxamide derivatives, as well as their compositions and methods of use. The compounds inhibit the activity of the Pim kinases, and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancer and other diseases.</p>
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ANTITUMOR DERIVATIVES FOR DIFFERENTIATION THERAPY (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">Imidazopyridine derivatives according to formula I are described</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="21.34mm" wi="69.85mm" file="US20170253589A1-20170907-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 X is selected from CH, N, S, and O, Y is selected from S, CO, and O, R<sup>1 </sup>and optional R<sup>2 </sup>are independently selected from H, OH, substituted or unsubstituted C<sub>1</sub>-C<sub>6 </sub>alkyl, and substituted or unsubstituted C<sub>4</sub>-C<sub>6 </sub>cycloalkyl or cycloheteroalkyl, R<sup>3 </sup>is selected from H, OH, substituted or unsubstituted C<sub>1</sub>-C<sub>6 </sub>alkyl, and optional Z is selected from OH, NH<sub>2</sub>, NH(CO)R<sup>4</sup>, NH(SO<sub>2</sub>)R<sup>4</sup>, guanidine, alkylguanidine, and fluoroguanidine, R<sup>4 </sup>is polyethylene glycol or substituted or unsubstituted C<sub>1</sub>-C<sub>6 </sub>alkyl, and pharmaceutically acceptable salt thereof. The imidazopyridine derivatives can be used for treatment of cancer in a subject.</li> </ul> </li> </ul> </p>
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AZETIDINYL PHENYL, PYRIDYL OR PYRAZINYL CARBOXAMIDE DERIVATIVES AS JAK INHIBITORS (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present invention provides azetidinyl phenyl, pyridyl, or pyrazinyl carboxamide derivatives, as well as their compositions and methods of use, that modulate the activity of Janus kinase (JAKs) and are useful in the treatment of diseases related to the activity of JAK including, for example, inflammatory disorders, autoimmune disorders, cancer, and other diseases.</p>
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Substituted Pyrrolidine Compounds (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present disclosure provides substituted pyrrolidine compounds having Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein R<sup>1</sup>, B, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="20.57mm" wi="59.77mm" file="US20170253601A1-20170907-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NITROGEN-CONTAINING ANALOGS OF SALINOMYCIN, SYNTHESIS AND USE AGAINST CANCER STEM CELLS AND MALARIA (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present invention concerns compounds of formula (I), enantiomers, mixture of enantiomers, diastereoisomers and mixture of diasteroisomers thereof formula (I): wherein at least one of W, X and Y is selected from the group consisting of —NR<sub>1</sub>R<sub>2</sub>; —NR<sub>3</sub>—(CH<sub>2</sub>)<sub>n</sub>—NR<sub>4</sub>R<sub>5</sub>; —O—(CH<sub>2</sub>)<sub>n</sub>—NR<sub>4</sub>R<sub>5</sub>; —NR<sub>3</sub>—(CH<sub>2</sub>)<sub>n</sub>—N′R<sub>6</sub>R<sub>7</sub>R<sub>8</sub>; and —O—(CH<sub>2</sub>)<sub>n</sub>—N′R<sub>6</sub>R<sub>7</sub>R<sub>8 </sub>and Z is a functional group capable of chelating iron salts. The present invention also concerns the compounds of formula (I) for use as a drug, in particular, in the treatment of cancer and malaria.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.98mm" wi="74.68mm" file="US20170253610A1-20170907-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NOVEL IMIDAZOPYRIDAZINE COMPOUNDS AND THEIR USE (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">This disclosure provides novel imidazopyridazine compounds of formula (I) and pharmaceutical acceptable salt thereof, pharmaceutical compositions containing them, a process for preparing them, and their practical effect in inhibiting PI<sub>3</sub>K and potential use in treating a disease responsive to inhibition of PI<sub>3</sub>K, for example, an inflammatory disease, autoimmune disease or cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="21.67mm" wi="57.40mm" file="US20170253618A1-20170907-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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2' AND/OR 5' AMINO-ACID ESTER PHOSPHORAMIDATE 3'-DEOXY ADENOSINE DERIVATIVES AS ANTI-CANCER COMPOUNDS (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">Disclosed are chemical compounds, the compounds for use in a method of treatment, particularly in a method of prophylaxis or treatment for cancer, a process for preparation of the compounds and pharmaceutical compositions comprising the compounds. The compounds may, in particular, be useful in the treatment of leukaemia, lymphoma and/or solid tumours in <i>homo sapiens</i>. The compounds are derivatives of cordycepin (3′-deoxyadenosine) having a 2′ and/or 5′-amino-acid ester phosphoramidate moiety.</p>
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Bicyclic heteroaryl derivatives as MNK1 and MNK2 modulators and uses thereof (Fri, 08 Sep 2017)
The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNKl a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.
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NOVEL TETRAHYDROPYRIDOPYRIMIDINE COMPOUND OR SALT THEREOF (Fri, 08 Sep 2017)
A method of treating a disease selected from the group consisting of ovarian cancer, bladder cancer, uterine cancer, pancreatic cancer, and hepatocellular cancer, comprising administering an effective amount of a tetrahydropyridopyrimidine compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof to a subject in need thereof: wherein, in the formula, X represents a halogen atom or a halogeno-C1 _3 alkyl group
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PYRIDYLPYRIDONE DERIVATIVE USEFUL AS A RET KINASE INHIBITOR IN THE TREATMENT OF IBS AND CANCER (Fri, 01 Sep 2017)
This invention relates to a novel compound which is an inhibitor of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing it, to processes for its preparation, and to its use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity. Formula (I)
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METHOD FOR GENERATING CELL-PENETRATING STAPLED PEPTIDES THAT LACK NONSPECIFIC MEMBRANE-LYTIC PROPERTIES FOR THERAPEUTIC TARGETING (Fri, 01 Sep 2017)
Methods for generating cell-permeable hydrocarbon-stapled and/or stitched peptides lacking nonspecific membrane lytic properties and methods for using such peptides to target cellular proteins for experimental investigation and/or therapeutic benefit.
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REDIRECTING IMMUNE RESPONSES (Fri, 01 Sep 2017)
Agents that specifically bind tumor-associated antigens (TAA) and comprise an exogenous polypeptide or peptide that can be presented by a tumor cell are disclosed. The TAA-binding agents may include antibodies and/or bispecific agents. Also disclosed are methods of using the agents for redirecting an existing immune response against tumor cells and/or treatment of diseases such as cancer.
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COMPOUNDS THAT INHIBIT MCL-1 PROTEIN (Fri, 01 Sep 2017)
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, 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.
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METHOD OF TREATMENT OF TP53 WILD-TYPE TUMORS WITH 2',2'-DIFLUORO-5-AZA-2'-DEOXYCYTIDINE OR PRODRUGS THEREOF (Fri, 01 Sep 2017)
This disclosure provides methods and strategies for inhibiting the growth of TP53 wild-type cancer cells, comprising contacting the cell with 2',2'-difluoro-5-aza-2'- deoxycytidine or a 2',2'-difluoro-5-aza-2'-deoxycytidine prodrug. Also provided are related methods for treating a cancer characterized by having wild-type TP53 in a subject in need thereof.
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PROCESS FOR MANUFACTURING 5-[[4-[[MORPHOLIN-2-YL]METHYLAMINO]-5-(TRIFLUOROMETHYL)- 2-PYRIDYL]AMINO]PYRAZINE-2-CARBONITRILE (Thu, 31 Aug 2017)
The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to 5-[[4-[[morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridyl]amino]pyrazine-2-carbonitrile compounds (referred to herein as "TFM compounds") which, inter alia , inhibit Checkpoint Kinase 1 (CHK1) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo , to inhibit CHK1 kinase function, and in the treatment of diseases and conditions that are mediated by CHK1, that are ameliorated by the inhibition of CHK1 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or a thymidylate synthase (TS) inhibitor; (d) a microtubule targeted agent; (e) ionising radiation; (f) an inhibitor of a mitosis regulator or a mitotic checkpoint regulator; (g) an inhibitor of a DNA damage signal transducer; or (h) an inhibitor of a DNA damage repair enzyme.
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NEW TYPE OF CYTIDINE DERIVATIVE AND APPLICATION THEREOF (Thu, 31 Aug 2017)
The present disclosure provides a new cytidine derivative having the general formula (I), and applications thereof: R1 As demonstrated by experiments on the growth inhibition effect of the new cytidine derivative of the present invention on HCT-116 colon cancer xenografts in tumor-bearing nude mice , the compound of the present invention has high anti-tumor activity, data of impacts on weight of nude mice bearing human colon cancer HCT-116 and data of mortality rate showed that the toxicity of the compound is comparatively low.
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METASTIN DERIVATIVE AND USE THEREOF (Thu, 31 Aug 2017)
Disclosed is a stable metastin derivative having excellent biological activities (e.g., a cancer metastasis inhibiting activity, a cancer proliferation inhibiting activity, a gonadotropin secretion promoting activity, a sex hormone secretion promoting activity). A metastin derivative produced by substituting a constituent amino acid in metastin can be improved in stability in the blood and can have an excellent cancer metastasis inhibiting activity, an excellent cancer proliferation inhibiting activity, an excellent gonadotropin secretion inhibiting activity, an excellent sex hormone secretion inhibiting activity and the like by binding the metastin derivative to polyethylene glycol.
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CONJUGATES OF PORPHYRINOID PHOTOSENSITIZERS AND GLYCEROL-BASED POLYMERS FOR PHOTODYNAMIC THERAPY (Thu, 31 Aug 2017)
Biologically active compounds that can be used as photosensitizers for diagnostic and therapeutic applications, particularly for PDT of cancer, infections and other hyperproliferative diseases, fluorescence diagnosis and PDT treatment of a non-tumorous indication such as arthritis, inflammatory diseases, viral or bacterial infections, dermatological, ophthalmological or urological disorders are provided as well as providing methods to obtain them in pharmaceutical quality. In addition, conjugates are provided in which these photosensitizers are attached to water-soluble polymers via cleavable linkers that can be cleaved in the body under specific conditions. Another embodiment consists of formulating the desired tetrapyrrole photosensitizer into a pharmaceutical formulation to be injected into the body avoiding undesirable effects like solubility problems or delayed pharmacokinetics of the tetrapyrrole systems.
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CONJUGATES OF CELL BINDING MOLECULES WITH CYTOTOXIC AGENTS (Thu, 31 Aug 2017)
A conjugate of a potent cytotoxic agent with a cell-surface receptor binding molecule having a formula (I), wherein T, L, m, n, Y, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 12 , and R 13 are defined herein, can be used for targeted treatment of cancer, autoimmune disease, and infectious disease.
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PHOSPHONATE COMPOUNDS (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to phosphonate compounds, compositions containing them, processes for obtaining them, and their use for treating a variety of medical disorders, e.g., osteoporosis and other disorders of bone metabolism, cancer, viral infections, and the like.</p>
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ARYLOXY PHENOXY ACRYLIC COMPOUND HAVING HIF-1 INHIBITION ACTIVITY, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS AN ACTIVE INGREDIENT (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to a compound inhibiting HF-1 activity, a preparation method of the same, and a pharmaceutical composition comprising the same as an active ingredient. The compound of the present invention demonstrates anticancer activity not by non-selective cytotoxicity but by inhibiting the activity of HIF-1, the transcription factor playing an important role in cancer cell growth and metastasis.</p> <p id="p-0002" num="0000">Accordingly, the compound or the pharmaceutically acceptable salt thereof according to the present invention inhibits HIF-1 activity, and therefore can be used as a therapeutic agent for solid tumors such as colon cancer, liver cancer, stomach cancer and breast cancer. In addition, the compound or the pharmaceutically acceptable salt thereof according to the present invention can be used as an active ingredient for a therapeutic agent for diabetic retinopathy or arthritis which may become worse when hypoxia-induced VEGF expression by HIF-1 increases.</p>
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Compositions and Related Methods for the Treatment of Cancer (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">Compositions and methods for the use thereof for the treatment of cancer in a subject in need thereof comprising administering to the subject an effective amount of a composition comprising an anticancer composition comprising a antineoplastic compound and a conjugated targeting moiety with or without a chemical linker. In certain aspects the antineoplastic compound is a platin and the conjugated targeting moiety is an amino acid.</p>
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FLUORESCENT SILICA-BASED NANOPARTICLES (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">The present invention provides a fluorescent silica-based nanoparticle that allows for precise detection, characterization, monitoring and treatment of a disease such as cancer. The nanoparticle has a range of diameters including between about 0.1 nm and about 100 nm, between about 0.5 nm and about 50 nm, between about 1 nm and about 25 nm, between about 1 nm and about 15 nm, or between about 1 nm and about 8 nm. The nanoparticle has a fluorescent compound positioned within the nanoparticle, and has greater brightness and fluorescent quantum yield than the free fluorescent compound. The nanoparticle also exhibits high biostability and biocompatibility. To facilitate efficient urinary excretion of the nanoparticle, it may be coated with an organic polymer, such as poly(ethylene glycol) (PEG). The small size of the nanoparticle, the silica base and the organic polymer coating minimizes the toxicity of the nanoparticle when administered in vivo. In order to target a specific cell type, the nanoparticle may further be conjugated to a ligand, which is capable of binding to a cellular component associated with the specific cell type, such as a tumor marker. In one embodiment, a therapeutic agent may be attached to the nanoparticle. To permit the nanoparticle to be detectable by not only optical fluorescence imaging, but also other imaging techniques, such as positron emission tomography (PET), single photon emission computed tomography (SPECT), computerized tomography (CT), bioluminescence imaging, and magnetic resonance imaging (MM), radionuclides/radiometals or paramagnetic ions may be conjugated to the nanoparticle.</p>
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PLASMA MEMBRANE CITRATE TRANSPORTER FOR USE IN THE DIAGNOSIS AND TREATMENT OF CANCER (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">The present invention is directed to a method for the diagnosis of cancer involving the plasma membrane citrate transporter (pmCiC). The invention is further directed to a modified substrate or modulator of pmCiC, the use of pmCiC as a tumor marker and a method of screening for a modulator of pmCiC activity.</p>
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SCREENING METHOD (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">The invention discloses a screening method for the identification of new compounds for use in the treatment of cancer.</p>
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N-((3,4,5-TRIMETHOXYSTYRYL)ARYL)CINNAMAMIDE COMPOUNDS AS POTENTIAL ANTICANCER AGENTS AND PROCESS FOR THE PREPARATION THEREOF (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">The present invention provides a compound of general formula A, useful as potential anticancer agents against human cancer cell lines and process for the preparation thereof. [Formula should be entered here] General formula A where in B selected from aryl, heteroaryl and fused heteroaryl ring R and X selected from H, hydroxy, alkyl, alkoxy, prop-2-ynyloxy, allyloxy, halo, alkylhalides, alkoxy halides, nitro, amine.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="52.75mm" wi="64.43mm" file="US20170240503A1-20170824-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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METHODS AND COMPOUNDS FOR RESTORING MUTANT p53 FUNCTION (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present invention can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.</p>
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HISTONE DEMETHYLASE INHIBITORS (Fri, 25 Aug 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 pancreatic cancer, prostate cancer, breast cancer, bladder cancer, lung cancer, gastric cancer, leukemia and/or melanoma and the like.</p>
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GADD45BETA/MKK7 INHIBITOR FOR THE TREATMENT OF A RESISTANT HAEMATOLOGICAL MALIGNANCY (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">A Gadd45β/MKK7 inhibitor for use in a method of treating a resistant haematological malignancy, combinations of said inhibitor with a further anti-cancer agent and related methods of use.</p>
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ANTIBODIES, COMPOSITIONS, AND USES (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">The present disclosure describes anti-B7H3 antibody agents and uses relating thereto. Among other things, the present disclosure demonstrates particular immunomodulatory effectiveness of certain such antibodies. The present disclosure further describes particularly high-affinity or otherwise useful antibodies and antibody agents based thereon, including particularly certain humanized and/or affinity matured versions of an 8H9 antibody. In some embodiments, provided antibody agents are useful, for example, in the treatment of cancer. In some embodiments, provided antibody agents are useful in relieving immunosuppression, for example mediated by B7H3-positive cells.</p>
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RAS EXON 2 SKIPPING FOR CANCER TREATMENT (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">There is provided SSOs targeting the region of HRAS, KRAS, and HRAS exon 2 that harbors the activating mutations and which harbors ESE activity. Moreover, there is provided SSOs targeting the 3′- and 5′-splice sites. The SSOs targeting the 5′ splice site sequence of HRAS exon 2, the 3′ splice site sequence of KRAS exon 2 and the 3′ splice site sequence of NRAS exon 2, as well as SSOs that targets ESEs in a conserved part of exon 2 in the HRAS, KRAS and NRAS exon 2 sequences can induce complete or nearly complete exon 2 skipping in cancer cell lines. This results in growth and proliferation inhibition and concomitantly in death of cancer cells. Therefore this invention is directed towards treatment of cancerous diseases and other conditions where RAS signaling is involved.</p>
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USE OF SILVER(I) COMPLEXES AS ANTICANCER AGENTS (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to the use of silver(I) monophosphine complexes as Active Pharmaceutical Ingredients (API's), including anticancer agents, for the treatment, diagnosis and/or prevention of cancer. The present invention also relates to pharmaceutical compositions containing such complexes and further extends to a method of treating or diagnosing a subject/patient suffering from cancer.</p>
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SMALL MOLECULE INHIBITORS OF N-TERMINUS ACTIVATION OF THE ANDROGEN RECEPTOR (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">Compounds having a structure of Formula (A) are provided. Uses of such compounds for treatment of various indications, including prostate cancer as well as methods of treatment involving such compounds are provided. Uses of compounds having a structure of Formula (F) for treatment of various indications, including prostate cancer as well as methods of treatment involving such compounds are also provided.</p>
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POLYCYCLIC INHIBITOR OF ANAPLASTIC LYMPHOMA KINASE (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">Disclosed is a polycyclic inhibitor of anaplastic lymphoma kinase as represented by Formula (I), or a pharmaceutically acceptable salt or stereoisomer thereof. Also disclosed is a method for preparing the compound, a pharmaceutical preparation and a pharmaceutical composition comprising the compound, and use of the compound, the pharmaceutically acceptable salt or stereoisomer thereof in manufacture of a medicament for the treatment and/or prevention of, for example, an anaplastic lymphoma kinase-mediated cancer or non-cancer related diseases.</p>
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ISOQUINOLINONE DERIVATIVES USEFUL IN THE TREATMENT OF CANCER (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to a compound of the following formula (I) or a pharmaceutically acceptable salt and/or solvate thereof, notably for use as a drug, notably in the treatment of cancer, as well as pharmaceutical compositions containing such a compound and processes to prepare such a compound.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="44.79mm" wi="69.85mm" file="US20170240544A1-20170824-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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HISTONE DEMETHYLASE INHIBITORS (Fri, 25 Aug 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 pyrido[3,4-d]pyrimidin-4-one derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.</p>
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BIFLUORODIOXALANE-AMINO-BENZIMIDAZOLE KINASE INHIBITORS FOR THE TREATMENT OF CANCER, AUTOIMMUNEINFLAMMATION AND CNS DISORDERS (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">The invention relates to a compound of the general formula (I) or a physiologically functional derivative, solvate or salt thereof,</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.80mm" wi="67.48mm" file="US20170240556A1-20170824-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein</p> <p id="p-0004" num="0000">A is a bond, alkyl or alkoxy optionally substituted with one or more R″ as defined herein, *—N(R′″)CO—, *—CON(R′″)—, *—N(R′″)CON(R′″)—, —S—, —SO—, *—N(R′″)—, *—N(R′″)CO—, *—CON(R′″)—, —CO—, *—COO—, *—OOC—, *—SO<sub>2</sub>N(R′″)—, —SO<sub>2</sub>, or *—N(R′″)—SO<sub>2</sub>—, wherein R′″ is as defined herein and * specifies the point of attachment to X; X is aryl, cycloalkyl, aralkyl, heterocyclyl or heteroaryl, which may be substituted with one or more R<sup>X </sup>further described herein; L is a bond or *—N(R<sup>N</sup>)CO—, *—CON(R<sup>N</sup>)—, *—N(R<sup>N</sup>)—, *—C═N(R<sup>N</sup>)—, *—N(R<sup>N</sup>)-alkyl-, *-alkyl-N(R<sup>N</sup>)—, *—N(R<sup>N</sup>)CON(R<sup>N</sup>)—, *—CO—, *—CO<sub>2</sub>—, alkyl, *-alkyl-O-alkyl-, *—NCO—CH═CH—, *—CH═CH—CONH—, *—SO<sub>2</sub>N(R<sup>N</sup>)—, *—N(R<sup>N</sup>)SO<sub>2</sub>—, or heterocyclyl, wherein * specifies the point of attachment to X; Y is H, alkyl, aryl, aralkyl, cycloalkyl, heterocyclyl or heteroaryl, which may be substituted with one or more R<sup>Y </sup>further described herein; and R and R<sup>N </sup>are further described herein; as well as their use as a medicament, a pharmaceutical composition comprising them, a method of treatment or prevention of a medical condition entailing the administration thereof, and the use thereof in the manufacture of a medicament for the treatment or prevention of a medical condition, particularly autoimmune inflammatory disorders, CNS disorders, sleeping disorders, or proliferative diseases including cancer. The invention further relates to a specific process for the preparation of said compounds.</p>
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SANGUINARINE ANALOG PP2C INHIBITORS FOR CANCER TREATMENT (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">Sanguinarine analogs as PP2C inhibitors are disclosed for the treatment of various cancers, as well as methods of synthesizing such analogs.</p>
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ETHYL N-BOC PIPERIDINYL PYRAZOLO PYRIDONES AS JANUS KINASE INHIBITORS (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">The instant invention provides compounds of Formula (I) which are JAK inhibitors, and as such are useful for the treatment of JAK-mediated diseases such as rheumatoid arthritis, asthma, COPD and cancer. The present invention provides novel compounds which are inhibitors of JAKs. The invention also provides a method for the treatment and prevention of JAK-mediated diseases and disorders using the novel compounds, as well as pharmaceutical compositions containing the compounds.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.40mm" wi="66.38mm" file="US20170240567A1-20170824-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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INTERNALIZING HUMAN MONOCLONAL ANTIBODIES TARGETING PROSTATE AND OTHER CANCER CELLS (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">In various embodiments various cancer specific antibodies and immunoconjugates are provided. In certain embodiments the antibodies specifically bind and are internalized into a prostate cancer cell, where the antibodies specifically binds cells that express or overexpress a CD46, and where the antibodies specifically bind sushi domain 1 of said CD46 (CD46 CPP1).</p>
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Aminomethylene pyrazolones with therapeutic activity (Fri, 25 Aug 2017)
<p id="p-0001" num="0000">A compound having the structure according to formula III</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.11mm" wi="70.78mm" file="US09790205-20171017-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein: <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">X is NH or S;</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is H or (1C-4C)alkyl;</li> <li id="ul0002-0003" num="0000">R<sup>2 </sup>is (1C-4C)alkyl, phenyl or a monocyclic aromatic ring having one or more N—, O— or S— atoms in the ring, which alkyl, phenyl or aromatic ring is optionally substituted with one or more groups selected from (1C-4C)alkyl, (1C-4C)alkyloxy, halo(1C-4C)alkyl, halo(1C-4C)alkyloxy, phenyloxy, phenylthio, halogen, or nitro;</li> <li id="ul0002-0004" num="0000">R<sup>3 </sup>and R<sup>4 </sup>are each independently H, (1C-6C)alkyl, (2C-6C) alkenyl, (2C-6C)alkynyl, cyano, (3C-6C)cycloalkyl, phenyl, a monocyclic aromatic ring having one or more N—, O— or S— atoms in the ring, a monocyclic non-aromatic ring having one or more N—, O— or S— atoms in the ring, each optionally substituted with hydroxyl, (1C-4C)alkoxy, phenyl, cycloalkyl, piperidyl, piperazinyl, furyl, thienyl, pirazinyl, pyrrolyl, 2H-pyrrolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyrrolidonyl, pyrrolinyl, imidazolinyl, imidazolyl, a monocyclic aromatic ring having one or more N—, O— or S— atoms in the ring, whereby each of these optional substituents is optionally further substituted with (1C-4C)alkyl, (1C-4C)alkyloxy, halo(1C-4C)alkyl, halo(1C-4C)alkyloxy, halogen, nitro or (1C-2C)dioxol forming a ring; or</li> <li id="ul0002-0005" num="0000">R<sup>3 </sup>and R<sup>4 </sup>form together pyrrolyl, imidazolyl, pyrazolyl, pyrrolidinyl, pyrrolinylimidazolidinyl, imidazolinyl, piperidyl, piperazinylmorpholinyl, each optionally substituted with (1C-6C)alkyl, phenyl(1C-4C)alkyl, phenylketo(1C-4C)alkyl;</li> <li id="ul0002-0006" num="0000">R<sup>5 </sup>is H, Cl, F, Br, Me, NO<sub>2</sub>, t-butyl, OCF<sub>3</sub>, OCH<sub>3</sub>, CF<sub>3</sub>;</li> <li id="ul0002-0007" num="0000">R<sup>6 </sup>is H, (1C-4C)alkyl, (1C-4C)alkyloxy, halo(1C-4C)alkyl, halo(1C-4C)alkyloxy, nitro or halogen;</li> <li id="ul0002-0008" num="0000">R<sup>7 </sup>is H, F, Cl, Br, Me, NO<sub>2</sub>, t-butyl, OCF<sub>3</sub>, OCH<sub>3</sub>, CF<sub>3</sub>; or</li> <li id="ul0002-0009" num="0000">pharmaceutically acceptable addition salts thereof for use in treatments of carcinoma, in particular, to delay, prevent or reverse metastasis in prostate cancer.</li> </ul> </li> </ul> </p>
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CARBOXAMIDE DERIVATIVES USEFUL AS RSK INHIBITORS (Fri, 25 Aug 2017)
Described herein are carboxamide derivatives that are useful as inhibitors of p90 ribosomal S6 kinase (RSK), pharmaceutical compositions comprising the derivatives, and methods of using the derivatives in treating diseases or conditions associated with RSK activity. Such carboxamide derivatives form bicyclic and tricyclic ring systems and the disease or condition associated with RSK activity in a mammal is cancer.
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FUSED 1,4-OXAZEPINES AND RELATED ANALOGS AS BET BROMODOMAIN INHIBITORS (Fri, 25 Aug 2017)
The present disclosure provides fused 1,4-oxazepines and related analogs represented by Formula (I) and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R1, R2a, R2b, R3a, R3b, R4, R5, A, and Y are as defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a condition or disorder responsive to inhibition of BET bromodomains such as cancer.
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TETRAHYDROQUINOLINE SUBSTITUTED HYDROXAMIC ACIDS AS SELECTIVE HISTONE DEACETYLASE 6 INHIBITORS (Fri, 25 Aug 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 neurological disease, traumatic brain injury, stroke, malaria, an autoimmune disease, autism, and inflammation, also are disclosed.
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6,7-DIHYDRO-5H-BENZO[7]ANNULENE DERIVATIVES AS ESTROGEN RECEPTOR MODULATORS (Fri, 25 Aug 2017)
The present invention relates to compounds of formula (I): wherein R1 and R2 represent hydrogen or deuterium atoms; R3 represents a hydrogen atom or a -COOH, a -OH or a -OPO(OH)2 group; R4 represents a hydrogen atom or a fluorine atom; R5 represents a hydrogen atom or a -OH group; wherein at least one of R3 or R5 is different from a hydrogen atom; when R3 represents a -COOH, -OH or -OPO(OH)2 group, then R5 represents a hydrogen atom; when R5 represents a -OH group, then R3 and R4 represent hydrogen atoms; and R6 is selected from an optionally substituted phenyl, heteroaryl, cycloalkyl or heterocycloalkyl group. The invention also relates to the preparation and to the therapeutic uses of the compounds of formula (I) as inhibitors and degraders of estrogen receptors, useful especially in the treatment of cancer.
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TAF1 INHIBITORS FOR THE THERAPY OF CANCER (Fri, 25 Aug 2017)
The present invention relates to lactam derivatives of formula (I) for use as medicaments as well as pharmaceutical compositions comprising these compounds, particularly for use as inhibitors of the bromodomain-containing protein TAF1 (i.e., transcription initiation factor TFIID subunit 1) and for use in the treatment or prevention of cancer.
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6-ARYL-4-MORPHOLIN-1-YLPYRIDONE COMPOUNDS USEFUL FOR THE TREATMENT OF CANCER AND DIABETES (Fri, 25 Aug 2017)
The invention provides novel 6-aryl or 6-heteroaryl 4-morpholin-4-yl-pyhdine-2-one compounds of formula (I), pharmaceutical compositions containing such compounds, and methods for using such compounds in treatment of diseases including cancer, diabetes, inflammatory diseases, neurodegenerative disorders, cardiovascular disorders and viral infections; wherein R1, R2, R3 and R4 are as defined in the specification.
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6-HETEROCYCLYL-4-MORPHOLIN-4-YLPYRIDINE-2-ONE COMPOUNDS USEFUL FOR THE TREATMENT OF CANCER AND DIABETES (Fri, 25 Aug 2017)
The invention provides novel 6-heterocyclyl-4-morpholin-4-yl-pyridine-2-one compounds of formula (I), pharmaceutical compositions containing such compounds, and methods for using such compounds in treatment of diseases including cancer, diabetes, inflammatory disease, neurodegenerative disorders, cardiovascular disorders and viral infections; wherein R1, R2, R3 and A are as defined in the specification.
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NOVEL COMPOUNDS (Fri, 25 Aug 2017)
The present invention relates to novel compounds of formula (I) and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of conditions involving mitochondrial dysfunction and in the treatment of cancer.
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METHYLAMINE DERIVATIVES AS LYSYSL OXIDASE INHIBITORS FOR THE TREATMENT OF CANCER (Fri, 25 Aug 2017)
Provided are compounds of the Formula (I), or a pharmaceutically acceptable salt thereof, wherein W, X, Y, Z, x, R1, R2, R3, x and n are defined in the specification. The compounds are inhibitors of lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) family members (LOXL1, LOXL2, LOXL3, LOXL4) and are useful in therapy, particularly in the treatment of cancer. Also disclosed are LOX inhibitors for use in the treatment of a cancer associated with EGFR and biomarkers that predict responsiveness to a LOX inhibitor.
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HISTONE DEMETHYLASE INHIBITORS (Fri, 25 Aug 2017)
This disclosure relates to compounds that inhibit histone demethylase activity. In particular, the disclosure relates to compounds that inhibit histone lysine demethylase KDM5B, pharmaceutical compositions and methods of use, such as methods of treating cancer using the compounds and pharmaceutical compositions disclosed herein.
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BCMA ANTIBODIES AND USE OF SAME TO TREAT CANCER AND IMMUNOLOGICAL DISORDERS (Fri, 25 Aug 2017)
The invention provides humanized antibodies that specifically bind to BCMA. The antibodies are useful for treatment and diagnoses of various cancers and immune disorders as well as detecting BCMA.
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COMPOSITIONS AND METHODS FOR TREATING LIVER CANCER (Fri, 25 Aug 2017)
Provided herein are compositions and methods of treating liver cancer by novel anticancer agents.
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ANTIFUNGAL COMPOUNDS AND USES THEREOF (Fri, 25 Aug 2017)
Provided herein are compounds (e.g., compounds of Formulae (I), (II), and (III)) which are anti-fungal agents and can be used in the treatment of diseases, including infectious diseases. The invention provides methods of treating diseases in a subject (e.g., infectious diseases such as fungal infections), and methods of killing or inhibiting the growth of fungi in or on a subject or biological sample. The compounds may be used in subjects, in clinical settings, or in agricultural settings.
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METHODS AND COMPOUNDS FOR RESTORING MUTANT p53 FUNCTION (Fri, 25 Aug 2017)
Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present invention can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.
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USES OF LABELED HSP90 INHIBITORS (Thu, 24 Aug 2017)
This invention concerns various methods of using labeled HSP90 inhibitors to improve treatment of cancer patients with HSP90 inhibitors, including ex vivo and in vivo methods for determining whether a tumor will likely respond to therapy with an HSP90 inhibitor. Regimens of the drug PU-H71 are also disclosed.
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SUBSTITUTED BENZOAZEPINES AS TOLL-LIKE RECEPTOR MODULATORS (Thu, 24 Aug 2017)
Provided are benzazepine derivatives useful for modulation of signaling through the Toll-like receptors TLR7 and/or TLR8. The benzazepine derivatives have use in treating or preventing disease, including cancer, autoimmune disease, fibrotic disease, cardiovascular disease, infectious disease, inflammatory disorder, graft rejection, or graft-versus-host disease.
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INHIBITORS OF C-FMS KINASE (Thu, 24 Aug 2017)
The invention is directed to compounds of Formula I: wherein Z, X, J, R 2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase. Methods of treating autoimmune diseases; and diseases with an inflammatory component; treating metastasis from ovarian cancer, uterine cancer, breast cancer, prostate cancer, lung cancer, colon cancer, stomach cancer, hairy cell leukemia; and treating pain, including skeletal pain caused by tumor metastasis or osteoarthritis, or visceral, inflammatory, and neurogenic pain; as well as osteoporosis, Paget's disease, and other diseases in which bone resorption mediates morbidity including rheumatoid arthritis, and other forms of inflammatory arthritis, osteoarthritis, prosthesis failure, osteolytic sarcoma, myeloma, and tumor metastasis to bone with the compounds of Formula I, are also provided.
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FUSED PYRIMIDINES AS INHIBITORS OF P97 COMPLEX (Thu, 24 Aug 2017)
Fused pyrimidine compounds having a saturated, unsaturated or aromatic A ring fused to a pyrimidine ring and having a complex substituents at the 2 position and a substituted amine at the 4 position of the pyrimidine ring as well as optional aliphatic, functional and/or aromatic components substituted at other positions of the pyrimidine ring and A ring are disclosed. These compounds are inhibitors of the AAA proteasome complex containing p97 and are effective medicinal agents for treatment of diseases associated with p97 bioactivity such as cancer.
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SUBSTITUTED BENZOAZEPINES AS TOLL-LIKE RECEPTOR MODULATORS (Thu, 24 Aug 2017)
Provided are compounds of formula (II) useful for modulation of signaling through the Toll-like receptors TLR7 and/or TLR8. The compounds have use in treating or preventing disease, including cancer, autoimmune disease, fibrotic disease, cardiovascular disease, infectious disease, inflammatory disorder, graft rejection, or graft-versus-host disease.
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Ferrocene derivative, preparation method and use thereof (Wed, 23 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to the ferrocene derivative represented by formula (IA) or formula (IB), or to the pharmaceutically acceptable salt or solvate thereof and to the pharmaceutical composition thereof. Wherein, R is independently selected from H, halogen, cyano, nitro, C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>alkoxy, hydroxy-C<sub>1</sub>-C<sub>6 </sub>alkyl, halo-C<sub>1</sub>-C<sub>6 </sub>alkyl, halo-C<sub>1</sub>-C<sub>6 </sub>alkoxy or C<sub>1</sub>-C<sub>6 </sub>alkoxy-C<sub>1</sub>-C<sub>6 </sub>alkoxy; Z is selected from O, S or NR<sub>1</sub>, wherein R<sub>1 </sub>is independently H or C<sub>1</sub>-C<sub>6 </sub>alkyl; n is an integer from 0 to 5. The present invention also provides a method and the pharmaceutical application thereof for preparing the compounds represented by formula (IA) or formula (IB) or the pharmaceutically acceptable salts thereof. The compounds have a strong inhibitory activity against human lung cancer cell line A549, colorectal cancer cell line HCT116 and/or breast cancer cell line MCF-7.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="94.83mm" wi="70.70mm" file="US09738673-20170822-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NOVEL SUBSTITUTED 6,7-DIHYDRO-5H-BENZO[7]ANNULENE COMPOUNDS, PROCESSES FOR THEIR PREPARATION AND THERAPEUTIC USES THEREOF (Fri, 18 Aug 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="59.86mm" wi="62.57mm" file="US20170233340A1-20170817-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R1 and R2 represent hydrogen or deuterium atoms; R3 represents a hydrogen atom or a —COOH, a —OH or a —OPO(OH)<sub>2 </sub>group; R4 represents a hydrogen atom or a fluorine atom; R5 represents a hydrogen atom or a —OH group; wherein at least one of R3 or R5 is different from a hydrogen atom; when R3 represents a —COOH, —OH or —OPO(OH)<sub>2 </sub>group, then R5 represents a hydrogen atom; when R5 represents a —OH group, then R3 and R4 represent hydrogen atoms; and R6 is selected from an optionally substituted phenyl, heteroaryl, cycloalkyl and heterocycloalkyl group; <br/> and the preparation and the therapeutic uses of the compounds of formula (I) as inhibitors and degraders of estrogen receptors, useful especially in the treatment of cancer. </p>
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INHIBITORS OF HIV-1 ENTRY AND METHODS OF USE THEREOF (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">The disclosure provides compositions and methods for sensitizing primary HIV-1, including transmitted/founder viruses, to neutralization by monoclonal antibodies, e.g., those directed against CD4-induced (CD4i) epitopes and the V3 region. In certain embodiments, the disclosure relates to the use of small molecules as microbicides to inhibit HIV-1 infection directly and to sensitize primary HIV-1 to neutralization by readily elicited antibodies.</p>
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NEW DERIVATIVES OF INDOLE FOR THE TREATMENT OF CANCER, VIRAL INFECTIONS AND LUNG DISEASES (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to a new class of indole derivatives, having a particular MKlp2 inhibition profile and useful as a therapeutic agent, in particular for the treatment of cancer, viral infections and lung diseases.</p>
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HSP70 MODULATORS AND METHODS FOR MAKING AND USING THE SAME (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">The present invention provides compounds I and II and compositions thereof for use in the modulation of Hsp70. In some embodiments, the present invention provides a method for inhibiting Hsp70 activity. In some embodiments, the present invention provides a method of treating a subject suffering from or susceptible to a disease, disorder, or condition responsive to Hsp70 inhibition comprising administering to the subject a therapeutically effective amount of a provided compound. In some embodiments, the present invention provides a method for treating or preventing cancer in a subject suffering therefrom, comprising administering to a patient in need thereof a therapeutically effective amount of a provided compound.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="44.28mm" wi="59.61mm" file="US20170233352A1-20170817-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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FLT3 RECEPTOR ANTAGONISTS (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">The invention pertains to novel FLT3 receptor antagonists of general formula (1). The compounds are useful for the treatment or the prevention of pain disorders, cancer and autoimmune diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.46mm" wi="64.01mm" file="US20170233354A1-20170817-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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ARYL AND HETEROARYL FUSED LACTAMS (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">This invention relates to compounds of general formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="47.33mm" wi="58.00mm" file="US20170233368A1-20170817-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">in which R<sup>1</sup>, R<sup>2</sup>, U, V, L, M, R<sup>5</sup>, m, X, Y and Z are as defined herein, and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.</p>
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IDO INHIBITORS (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the invention.</p>
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GOLD(I) COMPLEXES WITH ANTICANCER PROPERTIES AND METHODS OF USE THEREOF (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">Monomeric and dimeric gold(I) complexes as anticancer agents. The gold(I) complexes are coordinated to mixed ligands: one phosphine-based ligand that may be monodentate or bidentate and at least one dithiocarbamate-based ligand that is monodentate. 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 are also provided.</p>
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AZA-HETEROARYL COMPOUNDS AS PI3K-GAMMA INHIBITORS (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">The present invention provides aza-heteroaryl derivatives of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="58.50mm" file="US20170232016A1-20170817-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and pharmaceutically acceptable salts thereof, wherein X, Y, Z, A, W, R<sup>4</sup>, R<sup>5</sup>, and R<sup>6 </sup>are defined herein, that inhibit the activity of phosphoinositide 3-kinases-gamma (PI3Kγ) and are useful in the treatment of diseases related to the activity of PI3Kγ including, for example, autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.</p>
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Guanine Analogs as Telomerase Substrates and Telomere Length Affectors (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">This invention relates to compounds useful for inhibiting telomere elongation. More specifically, the invention provides nucleotide analogs that are incorporated into telomeres by telomerase thereby inhibiting elongation of telomeres. The compounds are use in treating cancer and other cell proliferative diseases.</p>
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COMPOSITIONS AND METHODS COMPRISING OSMIUM FOR THE TREATMENT OF CANCERS (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">Compositions and methods comprising osmium are provided. In some embodiments, the osmium compounds comprise a bidentate ligand. In some embodiments, the osmium compounds are used in method for treating cancer.</p>
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PT (IV) Complexes Containing 4,4'-Disubstituted-2,2'-Bipyridyl and Their Use in Cancer Therapy (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">Platinum-containing compounds for the treatment of disease, such as, for example, cancer, are provided herein. Specifically, platinum Pt(IV) complexes with a substituted 2,2′-bipyridine ring structure are provided, as are methods for using the complexes. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.</p>
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NUCLEOSIDE ANALOGS FOR TREATMENT OF THE FLAVIVIRIDAE FAMILY OF VIRUSES AND CANCER (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">The present invention is directed to compounds, compositions and methods for treating or preventing Flaviviridae family of viruses (including HCV, Yellow fever, Dengue, Chikungunya and West Nile virus), RSV, HEV, and influenza infection and cancer in human subjects or other animal hosts.</p>
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Novel Compounds (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">A compound of Formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="54.02mm" wi="75.86mm" file="US20170233430A1-20170817-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein Y<sup>1</sup>, Y<sup>2</sup>, X<sup>1</sup>, X<sup>2</sup>, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>8</sup>, and R<sup>9 </sup>are as defined herein; <br/> and pharmaceutically acceptable salts and tautomers thereof, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, in the treatment of diseases in which modulation of STING (Stimulator of Interferon Genes) is beneficial, for example inflammation, allergic and autoimmune diseases, infectious diseases, cancer, pre-cancerous syndromes and as vaccine adjuvants. </p>
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BENZODIAZEPINE DIMERS, CONJUGATES THEREOF, AND METHODS OF MAKING AND USING (Fri, 18 Aug 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="69.85mm" file="US20170233436A1-20170817-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="72.47mm" wi="69.85mm" file="US20170233436A1-20170817-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>
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REDUCTION SENSITIVE BIODEGRADABLE POLYESTERAMIDES (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to biodegradable polyesteramides (PEAs) comprising hydrophobic alpha-amino acids, diols, aliphatic dicarboxylic acids and optionally diamines whereby at least one of the dicarboxylic acids, diols or diamines comprises disulphide linkages. The present invention also relates to the use of the polyesteramides in medical applications such as cancer treatment, ophthalmic applications, therapeutic cardiovascular applications, veterinary applications, pain management applications, MSK applications and vaccine delivery compositions. The present invention also relates to a drug delivery composition comprising the PEA's and to a drug delivery system such as micro- or nanoparticles, micelles, liposomes, polymerosomes, micro- and nanogels, polymerosomes or nanotubes.</p>
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NOVEL ANTI-CXCR4 ANTIBODY AND ITS USE FOR THE DETECTION AND DIAGNOSIS OF CANCER (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">The present invention provides a novel, isolated anti-CXCR4 antibody for use in the diagnosis of cancer. In particular, the antibody of the invention recognizes monomeric and homodimeric CXCR4, but not heterodimeric CXCR4</p>
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CANCER THERAPEUTICS (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">This invention relates to compounds that bind to wild-type CBFβ and inhibit CBFβ binding to RUNX proteins. The potent compounds of the invention inhibit this protein-protein interaction at low micromolar concentrations, using allosteric mechanism to achieve inhibition, displace wild-type CBFβ from RUNX1 in cells, change occupancy of RUNX1 on target genes, and alter gene expression of RUNX1 target genes. These inhibitors show clear biological effects consistent with on-target RUNX protein activity. Pharmaceutical compositions containing a compound of the invention and a pharmaceutically acceptable carrier represent a separate embodiment of the invention. Another embodiment of the invention are methods of treating a RUNX-signaling-dependent cancer that expresses wild-type CBFβ in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention. In one embodiment, the cancer is selected from the group consisting of a RUNX-signaling-dependent leukemia that expresses wild-type CBFβ, lung cancer, bladder cancer, ovarian cancer, uterine cancer, endometrial cancer, breast cancer, liver cancer, pancreatic cancer, stomach cancer, cervical cancer, lymphoma, leukemia, acute myeloid leukemia, acute lymphocytic leukemia, salivary gland cancer, bone cancer, brain cancer, colon cancer, rectal cancer, colorectal cancer, kidney cancer, skin cancer, melanoma, squamous cell carcinoma of the tongue, pleomorphic adenoma, hepatocellular carcinoma, pancreatic cancer, squamous cell carcinoma, and/or adenocarcinoma. In another embodiment, the compounds of the invention can be used to treat a leukemia, lung cancer, ovarian cancer, and/or breast cancer.</p>
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NOVEL COMPOUNDS AS ROR GAMMA MODULATORS (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">The present disclosure is directed to compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein ring A, ring B, L, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>a</sup>, R<sup>b</sup>, n, m, p and q are as defined herein, which are active as modulators of retinoid-related orphan receptor gamma t (RORγt). These compounds prevent, inhibit, or suppress the action of RORγt and are therefore useful in the treatment of RORγt mediated diseases, disorders, syndromes or conditions such as, e.g., pain, inflammation, COPD, asthma, rheumatoid arthritis, colitis, multiple sclerosis, psoriasis, neurodegenerative diseases and cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.70mm" wi="75.44mm" file="US20170233380A1-20170817-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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HETEROARYLENE-BRIDGED BENZODIAZEPINE DIMERS, CONJUGATES THEREOF, AND METHODS OF MAKING AND USING (Fri, 18 Aug 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="38.52mm" wi="75.95mm" file="US20170233392A1-20170817-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein X comprises a heteroaromatic moiety and is as further defined in the application; <br/> R<sup>1 </sup>is </p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="74.85mm" wi="69.85mm" file="US20170233392A1-20170817-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005" num="0000">and the other variables in formulae (I), (Ia), and (Ib) are as defined in the application. Such dimers are useful as anti-cancer agents, especially when used in an antibody-drug conjugate (ADC).</p>
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TRICYCLIC P13K INHIBITOR COMPOUNDS AND METHODS OF USE (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">Tricyclic PI3k inhibitor compounds of Formula I with anti-cancer activity, anti-inflammatory activity, or immunoregulatory properties, and more specifically with PI3 kinase modulating or inhibitory activity are described. Methods are described for using the tricyclic PI3K inhibitor compounds of Formula I for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, organisms, or associated pathological conditions.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.15mm" wi="70.02mm" file="US20170233407A1-20170817-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">Formula I compounds include stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof. The dashed lines indicate an optional double bond, and at least one dashed line is a double bond. The substituents are as described.</p>
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THIAZOLYL-CONTAINING COMPOUNDS FOR TREATING PROLIFERATIVE DISEASES (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">The present disclosure provides thiazolyl-containing compounds of Formula (I), (II), or (III). The compounds described herein may be able to inhibit protein kinases (e.g., Src family kinases (e.g., hemopoietic cell kinase (HCK)), Bruton's tyrosine kinase (BTK)) and may be useful in treating and/or preventing proliferative diseases (e.g., myelodysplasia, leukemia, lymphoma (e.g., Waldenstrom's macroglobulinemia)) and in inducing apoptosis in a cell (e.g., malignant blood cell). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="100.58mm" wi="73.15mm" file="US20170233411A1-20170817-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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BCMA ANTIBODIES AND USE OF SAME TO TREAT CANCER AND IMMUNOLOGICAL DISORDERS (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">The invention provides humanized antibodies that specifically bind to BCMA. The antibodies are useful for treatment and diagnoses of various cancers and immune disorders as well as detecting BCMA.</p>
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INTERNALIZING HUMAN MONOCLONAL ANTIBODIES TARGETING PROSTATE CANCER CELLS IN SITU (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">This invention provides a method that allows selection of antibodies against cells (e.g., tumor cells) in situ using laser capture microdissection. By restricting antibody selection to binders of internalizing epitopes, a panel of phage antibodies was generated that targets clinically represented prostate cancer antigens.</p>
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Antithrombotic Compounds, Methods and Uses Thereof (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">Provided herein are polymers and methods for their use in binding a phosphate containing biological macromolecules. Specifically, the methods and uses provided herein may be used to inhibit thrombin binding to polyphosphate or as an antithrombotic agent for the treatment of stroke, acute coronary syndrome, pulmonary embolism, atrial fibrillation, venous and arterial thromboembolism, disseminated intravascular coagulation (DIC), deep-vein thrombosis (DVT), peripheral artery disease, trauma-induced coagulopathy, extracorporeal circulation, cancer-associated thrombosis, sepsis, septic shock, Systemic Inflammatory Response Syndrome (SIRS), or inflammation.</p>
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IMMUNE REGULATORY OLIGONUCLEOTIDE (IRO) COMPOUNDS TO MODULATE TOLL-LIKE RECEPTOR BASED IMMUNE RESPONSE (Fri, 18 Aug 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>
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QUATERNARY AMINE COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">This invention relates to quaternary amine linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.</p>
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COMPOSITIONS AND METHODS FOR IDENTIFICATION, ASSESSMENT, PREVENTION, AND TREATMENT OF T-CELL EXHAUSTION USING CD39 BIOMARKERS AND MODULATORS (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">The present invention is based on the identification, of compositions and methods for the identification, assessment, prevention, and treatment of T-cell exhaustion using CD39 biomarkers and modulators.</p>
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HALOALLYLAMINE INDOLE AND AZAINDOLE DERIVATIVE INHIBITORS OF LYSYL OXIDASES AND USES THEREOF (Fri, 18 Aug 2017)
The present invention relates to novel compounds which are capable of inhibiting certain amine oxidase enzymes. These compounds are useful for treatment of a variety of indications, e.g., fibrosis, cancer and/or angiogenesis in human subjects as well as in pets and livestock. In addition, the present invention relates to pharmaceutical compositions containing these compounds, as well as various uses thereof.
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INDOLE AND AZAINDOLE HALOALLYLAMINE DERIVATIVE INHIBITORS OF LYSYL OXIDASES AND USES THEREOF (Fri, 18 Aug 2017)
The present invention relates to novel compounds which are capable of inhibiting certain amine oxidase enzymes. These compounds are useful for treatment of a variety of indications, e.g., fibrosis, cancer and/or angiogenesis in human subjects as well as in pets and livestock. In addition, the present invention relates to pharmaceutical compositions containing these compounds, as well as various uses thereof.
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BIOCONJUGATES CONTAINING SULFAMIDE LINKERS FOR USE IN TREATMENT (Fri, 18 Aug 2017)
The present invention is based on the surprising finding that the linker employed in a bioconjugate, such as an anti-body-drug conjugate, is not therapeutically inert but has an effect on the therapeutic index of the bioconjugate. The present invention thus concerns a method for increasing the therapeutic index of a bioconjugate and the bioconjugates for use in treatment, in particular cancer. The bioconjugates according to the invention have a sulfamide linker comprising a group according to formula (1).
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CELLULAR SIGNALLING INHIBITORS, THEIR FORMULATIONS AND METHODS THEREOF (Fri, 18 Aug 2017)
The present disclosure relates generally to Cellular Signalling inhibitors of compound of Formula (I), compositions and formulations comprising the same, methods, processes, and uses thereof. In particular, the present disclosure provides CSF-1R inhibitors demonstrating sustained inhibition of CSF/CSF1R signalling pathway with decreased toxicity. The present disclosure also provides supramolecular combinatorial therapeutics, wherein a CSF-1R inhibitor is combined with one or more of a chemotherapeutic agent, a kinase inhibitor, and an immunoregulator, each of which is optionally conjugated with a lipid. The present disclosure also provides a method for treating cancer, allergy, Systemic lupus erythematosus, nephritis, Chronic Obstructive Pulmonary Disease, and abnormal macrophage functions or any combinations thereof.
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COMPOSITIONS AND METHODS FOR INHIBITING KINASE ACTIVITY (Fri, 18 Aug 2017)
The present invention features therapeutic compositions comprising an agent that specifically binds to a PIF pocket of Aurora A kinase and an agent that specifically binds to an ATP-binding site of Aurora A kinase, and the use of the therapeutic compositions to modulate Aurora A kinase for the treatment of cancer.
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INHIBITOR OF INDOLEAMINE-2,3-DIOXYGENASE (IDO) (Fri, 18 Aug 2017)
The present disclosure provides compounds of Formula (I). The compounds described herein may be useful in treating a disease associated with IDO, for example, cancer or an infectious disease (e.g., viral or bacterial infectious diseases). Also, provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.
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METHOD OF SENSITIZING CANCER CELLS TO THE CYTOTOXIC EFFECTS OF APOPTOSIS INDUCING LIGANDS IN CANCER TREATMENT (Fri, 18 Aug 2017)
Disclosed is a method of enhancing the response of cancer cells in a mammal to treatment with an apoptosis inducing ligand, which method comprises contacting the cancer cells with an apoptosis inducing ligand in conjunction with an effective amount of a compound of the formula: (I), wherein R1-R14 are as described herein. Also disclosed is a method of inducing apoptosis in cancer cells in a mammal, comprising contacting the cancer cells with the compound described herein and also contacting the cancer cells with an apoptosis inducing ligand, whereby apoptosis is induced in the cancer cells.
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EGFR INHIBITOR, AND PREPARATION AND APPLICATION THEREOF (Thu, 17 Aug 2017)
A 4-substituted-2-(N-(5-substituted allyl amide)phenyl)amino)pyrimidine derivative as represented by formula (I), and a preparation and application thereof as an EGFR inhibitor. The compound has activity of inhibiting the L858R EGFR mutant, the T790M EGFR mutant and the exon 19 deletion activating mutant, may be used to treat diseases mediated alone or in part by EGFR mutant activity, and has a wide application in drugs preventing and treating cancers, particularly non-small cell lung cancer.
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MACROCYCLIC COMPOUNDS AS TRK KINASE INHIBITORS (Thu, 17 Aug 2017)
Compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, D, R 2 , R 2a , R 3 , R 3a , and Z 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.
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OSMIUM (II) ARENE IMINO ANTI-CANCER COMPLEXES (Thu, 17 Aug 2017)
The present invention relates to the use of certain osmium containing complexes such as cytotoxic agents particularly for the treatment of cancer. There is also provided novel osmium containing complexes, as well as pharmaceutical formulations comprising such complexes.
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2-(PYRIMIDIN-5-YL)-THIOPYRIMIDINE DERIVATIVES AS HSP70 AND HSC70 MODULATORS FOR THE TREATMENT OF PROLIFERATIVE DISORDERS (Thu, 17 Aug 2017)
The present invention relates to 2-(Pyrimidin-5-yl)-thiopyrimidine derivatives as Hsp70 and Hsc70 modulators for the treatment of proliferative disorders.
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USE OF FATTY ACIDS IN METHODS FOR DETECTING CANCER (Thu, 17 Aug 2017)
Methods to determine the absence or presence of one or more cancer types in an animal are disclosed herein. In some embodiments, amounts of lipids in a sample (e.g., a bodily fluid or treatment thereof) from the animal are used with a predictive model to make the determination. The lipid amounts can be measured, in some instances, using a mass spectrometry system.
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BICYCLIC HETEROCYCLE COMPOUNDS AND THEIR USES IN THERAPY (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">The invention relates to new bicyclic heterocycle compounds, to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.</p>
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IDENTIFICATION OF IMMUNOLOGICALLY PROTECTIVE NEO-EPITOPES FOR THE TREATMENT OF CANCERS (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">Described herein are methods of identifying immunologically protective neo-epitopes from the cancer tissue DNA of cancer patients using biophysical principles as well as bioinformatics techniques. The identification of immunologically protective neo-epitopes provides pharmaceutical compositions with a limited number of tumor-specific peptides suitable for personalized genomics-driven immunotherapy of human cancer. Specifically disclosed herein is a method of using the conformational stability of an epitope in an MHC protein-binding groove to predict immunogenicity of peptides in a putative neo-peptide set from a tumor from a cancer patient. Pharmaceutical compositions and methods of administration are also included.</p>
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Methods of Use for Trisubstituted Benzotriazole Derivatives as Dihydroorotate Oxygenase Inhibitors (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">The present invention provides methods for treating a cancer in a subject and for inhibiting tumor growth, metastasis or a dihydrorotate oxygenase enzyme activity of a tumor or cancer cell. At least one trisubstituted benzotriazole derivative with the formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.06mm" wi="69.85mm" file="US20170224663A1-20170810-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">is administered to the subject or is contacted with the cancer cell. Compounds of formula (I) have substituents R<sub>1</sub>, R<sub>2 </sub>and R<sub>3 </sub>which have the meanings given in the specification, and pharmaceutically acceptable salts thereof.</p>
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3-(1H-IMIDAZO[4,5-C]PYRIDIN-2-YL)-1H-PYRAZOLO[3,4-B]PYRIDINE AND THERAPEUTIC USES THEREOF (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an azaindazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.</p>
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USES OF SALT-INDUCIBLE KINASE (SIK) INHIBITORS (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">The present disclosure provides methods of treating and/or preventing inflammatory bowel disease (IBD) and graft-versus-host disease (GVHD) using salt-inducible kinase (SIK) inhibitors, such as macrocyclic SIK inhibitors of Formula (I), imidazolyl SIK inhibitors of Formula (II), and urea and carbamate SIK inhibitors of Formula (III-A) (e.g., urea and carbamate SIK inhibitors of Formula (III)).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="176.02mm" wi="71.54mm" file="US20170224700A1-20170810-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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TROPOMYOSIN-RELATED KINASE (TRK) INHIBITORS (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">Tropomyosin-related kinase inhibitors (Trk inhibitors) are small molecule compounds useful in the treatment of disease. Trk inhibitors can be used as pharmaceutical agents and in pharmaceutical compositions. Trk inhibitors are useful in the treatment of inflammatory diseases, autoimmune disease, defects of bone metabolism and/or cancer, and are particularly useful in the treatment of osteoarthritis (OA), pain, and pain associated with OA. Trk inhibitors are also useful for inhibiting tropomyosin-related kinase A (TrkA), tropomyosin-related kinase B (TrkB), tropomyosin-related kinase C (TrkC), and/or c-FMS (the cellular receptor for colony stimulating factor-1 (CSF-1)).</p>
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10-SUBSTITUTED COLCHICINOIDS AS POTENT ANTICANCER AGENTS (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to the compounds of formula I wherein R is as herein described. The present invention particularly relates to synthesis and antiproliferative activity of 10-substituted colchicinoids. Compounds of the invention can be used for prevention or in the treatment of cancer disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.68mm" wi="61.72mm" file="US20170226051A1-20170810-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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POTENT DUAL BRD4-KINASE INHIBITORS AS CANCER THERAPEUTICS (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">Disclosed herein are compounds that are inhibitors of BRD4 and their use in the treatment of cancer. Methods of screening for selective inhibitors of BRD4 are also disclosed. In certain aspects, disclosed are compounds of Formula I-IV.</p>
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PIPERAZINE DERIVATIVES AS LIVER X RECEPTOR MODULATORS (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">Provided are novel compounds of Formula (I): pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are liver X receptor modulators, and which are useful in the treatment of diseases and disorders associated with the liver X receptor. Also provided are the compounds of Formula (I) and pharmaceutical compositions thereof for treating atherosclerosis, cardiovascular disease, Alzheimer's disease, dermatitis, dyslipidemia, cancer and other diseases or disorders.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="60.45mm" file="US20170226067A1-20170810-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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HETEROCYCLE-SUBSTITUTED PYRIDYL BENZOTHIOPHENES AS KINASE INHIBITORS (Fri, 11 Aug 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="69.85mm" file="US20170226094A1-20170810-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt thereof, wherein R<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>
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COMPOUNDS FOR PREVENTING, INHIBITING, OR TREATING CANCER, AIDS AND/OR PREMATURE AGING (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">The manufacture and use of compounds of formula (Ia) or a pharmaceutically acceptable salt thereof for preventing, inhibiting or treating cancer, AIDS and/or premature aging. The compounds of formula (Ia) being:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="20.91mm" wi="69.85mm" file="US20170226095A1-20170810-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">where: <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 independently represents a hydrogen atom, a halogen atom, a (C<sub>1</sub>-C<sub>3</sub>)alkyl group, a —CN group, a hydroxyl group, a —COOR<sub>1 </sub>group, a (C<sub>1</sub>-C<sub>3</sub>)fluoroalkyl group, a —NO<sub>2 </sub>group, a —NR<sub>1</sub>R<sub>2 </sub>group, or a (C<sub>1</sub>-C<sub>3</sub>)alkoxy group;</li> <li id="ul0002-0002" num="0000">R′ is a hydrogen atom, a halogen atom, a (C<sub>1</sub>-C<sub>3</sub>)alkyl group, a —NO<sub>2 </sub>group, a (C<sub>1</sub>-C<sub>3</sub>)alkoxy group, or a —NR<sub>1</sub>R<sub>2 </sub>group; and</li> <li id="ul0002-0003" num="0000">R<sub>1 </sub>and R<sub>2 </sub>are a hydrogen atom or a (C<sub>1</sub>-C<sub>3</sub>) alkyl group.</li> </ul> </li> </ul> </p>
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SELECTIVE INHIBITORS OF CONSTITUTIVE ANDROSTANE RECEPTOR (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">The compounds of the invention are antagonists of CAR, with specificity for CAR over other proteins including PXR. The disclosed compounds are useful in treating or controlling cell proliferative disorders, in particular oncological disorders, such as cancer. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.</p>
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Factor D Inhibitors Useful for Treating Inflammatory Disorders (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">Compounds, methods of use, and processes for making inhibitors of complement factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof are provided. The inhibitors described herein target factor D and inhibit or regulate the complement cascade at an early and essential point in the alternative complement pathway, and reduce factor D's ability to modulate the classical and lectin complement pathways. The inhibitors of factor D described herein are capable of reducing the excessive activation of complement, which has been linked to certain autoimmune, inflammatory, and neurodegenerative diseases, as well as ischemia-reperfusion injury and cancer.</p>
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INHIBITORS OF TRYPTOPHAN DIOXYGENASES (IDO1 and TDO) AND THEIR USE IN THERAPY (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">Pharmaceutical compositions comprising 3-aminoisoxazolopyridine compounds of the Formula I having IDO1 and/or TDO inhibitory activity are described, where W is CR<sup>1</sup>, N or N-oxide; X is CR<sup>2</sup>, N or N-oxide; Y is CR<sup>3</sup>, N or N-oxide; Z is CR<sup>4</sup>, N or N-oxide; and at least one of W, X, Y, and Z is N or N-oxide; and R<sup>9 </sup>and R<sup>10 </sup>are as defined. Also described are methods of using such compounds in the treatment of various conditions, such as cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.15mm" wi="52.15mm" file="US20170224701A1-20170810-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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METHODS AND COMPOSITIONS FOR GAMMA-GLUTAMYL CYCLE MODULATION (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">The present disclosure provides pharmaceutical compositions comprising Gamma-glutamyl cycle inhibitors (GGCI) and certain pharmaceutically acceptable salts thereof, and methods of use.</p>
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COMPOUNDS AND METHODS FOR TREATING CANCER (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">This document provides compounds, compositions, and methods for treating cancers including renal cancer (e.g., renal cell carcinoma) as well as ovarian, breast, prostate, colon, pancreatic, bladder, liver, lung, and thyroid cancers and melanoma. For example, compounds, compositions, and methods for using one or more inhibitors of SCD1 to treat renal cell carcinoma (e.g., clear cell renal cell carcinoma (ccRCC)), thyroid cancer, or liver cancer; or to increase the efficacy of treatment for the same.</p>
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