Cancer

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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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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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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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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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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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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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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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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CURCUMIN-SOPHOROLIPID COMPLEX (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to a complex comprising acidic sophorolipid and curcumin ((SL(A)+Cur), wherein, curcumin is solubilized and nano-encapsulated in acidic sophorolipid to improve the water solubility, stability and bioavailability of curcumin in order to enhance its therapeutic activity. Further, the invention provides pharmaceutical compositions comprising the present complex and methods to treat cancer in a subject using the said composition.</p>
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PAK1-Activation Blocking Compounds, Preparation Thereof and Methods of Use (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to a PAK1 blocking compound having a much higher bioavailability and cell permeability than traditional herbal PAK1 blockers or synthetic PAK1 blockers, and the uses thereof for treating cancer or other PAK1 dependent diseases or disorders. This PAK1 blocking compound comprises an ester of an acidic PAK1 blocker, or a pharmaceutically acceptable salt thereof. This PAK1-blocking ester may be prepared by esterifying a PAK1 blocker starting material with an alcohol; and treating the esterified PAK1 blocker with an aromatic azide to generate a 1,2,3-triazolyl derivative.</p>
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NANOPARTICLE-BASED TUMOR-TARGETED DRUG DELIVERY (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">An aqueous tumor-targeting liposome nanoparticle composition comprises an aqueous dispersion of liposome nanoparticles. The nanoparticles preferably encapsulate an anti-cancer chemotherapeutic agent, which can be added to a pre-formed liposome composition or can be incorporated in the liposomes during the formation of the liposomes. The liposome nanoparticles comprise a legumain-targeting lipid admixed with one or more other micelle or vesicle-forming lipid materials in the form of nanoparticulate liposomes dispersed in an aqueous carrier. A preferred tumor-targeting liposome nanoparticle composition comprises a legumain-targeting lipid component and polyethylene glycol-conjugated lipid component. The legumain-targeting lipid component comprising a hydrophobic lipid portion covalently attached to a legumain-binding moiety.</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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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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METHOD FOR TREATING OVARIAN CANCER AND/OR HODGKIN LYMPHOMIA WITH A GOLD(III) COMPLEX (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">A method for treating cancer and gold(III) complexes with diaminocyclohexane ligand as anticancer agents. Also described are a pharmaceutical composition incorporating the gold(III) complexes and a method of synthesizing the gold(III) complexes.</p>
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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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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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COMPOUNDS FOR TREATMENT OF CANCER (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to novel compounds having anti-cancer activity, methods of making these compounds, and their use for treating cancer and drug-resistant tumors, e.g. melanoma, metastatic melanoma, drug resistant melanoma, prostate cancer and drug resistant prostate cancer.</p>
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QUINAZOLINE DERIVATIVE (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">Provided are a quinazoline derivative, a pharmaceutical composition containing the same, a method for preparation of said derivative, and an application of same as an anti-cancer drug.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.10mm" wi="67.73mm" file="US20170226099A1-20170810-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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INHIBITORS OF ERK AND METHODS OF USE (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">The present invention provides chemical entities or compounds and pharmaceutical compositions thereof that are capable of modulating certain protein kinases such as ERK (MAPK). Also provided are methods of using such compounds or compositions, and methods of using these compositions to modulate the activities of one or more of these kinases, especially for therapeutic applications such as the treatment disorders such as cancer.</p>
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Ataxia Telengiectasia And Rad3-Related (ATR) Protein Kinase Inhibitors (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">Macrocyclic compounds having the structure of Formula (A), or pharmaceutically acceptable salts thereof, are provided,</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.94mm" wi="53.93mm" file="US20170226130A1-20170810-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and R<sup>5 </sup>are defined herein. Also provided are pharmaceutical compositions comprising the macrocyclic compound and methods for treating cancer in a patient comprising administering to the patient the macrocyclic compound.</p>
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HETEROCYCLIC COMPOUNDS, METHODS OF SYNTHESIS AND USES THEREOF (Fri, 11 Aug 2017)
The present invention relates to 3-quinolinecarbonitrile compounds of formula (I) disclosed herein, methods for their synthesis, and uses thereof. Advantageously, the disclosed heterocyclic compounds may demonstrate enhanced efficacy in antitumor properties. Hence, the present disclosure also relates to the use of the disclosed 3-quinolinecarbonitrile compounds or pharmaceutical compositions thereof in cancer treatment.
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COMPOUNDS, COMPOSITIONS AND METHODS FOR CANCER PATIENT STRATIFICATION AND CANCER TREATMENT (Fri, 11 Aug 2017)
The present invention features improved Compounds, especially (I) methods of identifying patients having Cancer using biomarkers (e.g., PDE3A, SLFN12 and/or CREB3Ll) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention (e.g., Compounds 1-6 disclosed herein).
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TUBULYSIN ANALOGS AND METHODS FOR THEIR PREPARATION (Fri, 11 Aug 2017)
The present invention is directed to novel cytotoxic tubulysin analogs and derivatives, to antibody drug conjugates thereof, and to methods for using the same to treat medical conditions including cancer.
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DERIVATIVES OF PYRROLOIMIDAZOLE OR ANALOGUES THEREOF WHICH ARE USEFUL FOR THE TREATMENT OF INTER ALIA CANCER (Fri, 11 Aug 2017)
Present invention relates to novel heterocyclic compounds as indoleamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3-dioxygenase (TDO) modulators. Compounds of the present invention inhibit tryptophan degradation by modulating IDO and/or TDO. Formula (I) The invention further relates to the process of their preparation, pharmaceutical composition and their use in modulating the activity of indoleamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3- dioxygenase (TDO). The compounds of the invention can be used alone or in combination for the treatment of conditions that benefits from the inhibition of tryptophan degradation.
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AMINOTHIAZOLE COMPOUNDS AND USE THEREOF (Fri, 11 Aug 2017)
Aminothiazole compounds of Formula (I) shown herein and pharmaceutical compositions containing one of such compounds. Also disclosed are methods, each of which uses one of the aminothiazole compounds to inhibit a protein kinase or to treat cancer associated with a protein kinase.
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MUTANT SMOOTHENED AND METHODS OF USING THE SAME (Fri, 11 Aug 2017)
The emergence of mutations in tyrosine kinases following treatment of cancer patients with molecular-targeted therapy represents a major mechanism of acquired drug resistance. Here, mutations in the serpentine receptor, Smoothened (SMO) are described, which result in resistance to a Hedgehog (Hh) pathway inhibitor, such as in medulloblastoma. Amino acid substitutions in conserved residues of SMO maintain Hh signaling, but result in the inability of the Hh pathway inhibitor, GDC-0449, to suppress the pathway. In some embodiments, the disclosure provides for novel mutant SMO proteins and nucleic acids and for screening methods to detect SMO mutations and methods to screen for drugs that specifically modulate mutant SMO exhibiting drug resistance.
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STAPLED PEPTIDE CONJUGATES AND PARTICLES (Fri, 11 Aug 2017)
Conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to a targeting moiety via a linker, and particles comprising such conjugates 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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PURINE COMPOUNDS POSSESSING ANTICANCER ACTIVITY (Fri, 11 Aug 2017)
The present disclosure provides compounds of Formulas (I') and (I), and pharmaceutically acceptable salts thereof. The compounds described herein may be useful in treating and/or preventing proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions, kits, and uses thereof for treating proliferative diseases.
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RAPAGLUTINS, NOVEL INHIBITORS OF GLUT AND USE THEREOF (Fri, 11 Aug 2017)
Compounds with the following structures and their analogs are provided. Compositions that include these structures can be used to inhibit glucose transporters and stop or decrease the proliferation of cancer, treat possible organ rejection and treat autoimmune disease.
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PEPTIDE DRUG CONJUGATES (Fri, 11 Aug 2017)
Embodiments provide protein-drug conjugates for treatment of cancer. Protein-drug conjugates may include protein-drug conjugates of Formula I: Ctx-L-Cp (I) or a pharmaceutically acceptable salt or solvate thereof, wherein: Ctx is chlorotoxin or a chlorotoxin analog; Cp is a cryptophycin amide, and L is a linker wherein the linker is bound to Ctx at an X2 moiety of the linker and at one of a lysine residue and the N-terminus of the chlorotoxin or chlorotoxin analog.
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SELECTIVE ESTROGEN RECEPTOR DEGRADERS AND USES THEREOF (Fri, 11 Aug 2017)
The present disclosure provides compounds of Formula (I) and Formula (II). The compounds described herein may be useful in treating proliferative diseases (e.g., cancer).Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein.
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POLYCYCLIC ANAPLASTIC LYMPHOMA KINASE INHIBITOR (Thu, 10 Aug 2017)
Provided is a polycyclic inhibitor of anaplastic lymphoma kinase as represented by Formula (I), or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 1 , R 2 , R 3 , R 4 , and ring A are as defined in the description. The invention also relates to 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 an anaplastic lymphoma kinase-mediated cancer or non-cancer related diseases.
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ISOXAZOLE DERIVATIVE AS MUTATED ISOCITRATE DEHYDROGENASE 1 INHIBITOR (Thu, 10 Aug 2017)
It has been found that a compound of the general formula (I) having an isoxazole skeleton has excellent inhibitory activity against mutant IDH1 protein and inhibits the production of 2-HG by this protein, while the compound is also capable of effectively inhibiting the growth of various tumors expressing the protein. In the formula, R 1 , R 2 , R 3 , Y, and Z are as defined in claim 1.
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CANCER CELL GROWTH INHIBITOR, ANTICANCER AGENT, AND METHOD FOR SCREENING SAME, AS WELL AS NOVEL COMPOUND (Thu, 10 Aug 2017)
A cancer cell proliferation inhibitor including at least one selected from compounds represented by Structural Formulae (1) to (8), wherein the cancer cell is at least one of a cancer cell overexpressing a wild-type epidermal growth factor receptor and a cancer cell expressing an epidermal growth factor receptor mutant vIII.
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SUBSTITUTED PYRROLOPYRIMIDINE COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH (Thu, 10 Aug 2017)
The present invention relates to a compound of formula (I): and pharmaceutically acceptable salts, tautomers, stereoisomers, enantiomers, and isotopologues thereof, wherein R 1 , R 2 , R 3 and L are as defined herein. Also provided is a compound or a pharmaceutical composition of the present invention for use in a method for treating or preventing breast cancer.
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POLYSACCHARIDE FOR USE IN PREVENTING METASTASIS FORMATION AND/OR RELAPSE (Thu, 10 Aug 2017)
The present invention relates to a polysaccharide comprising, optionally substituted, monosaccharide units linked via alpha-glycosidic bonds for use in preventing metastasis formation and/or relapse by administration to a body cavity of a subject afflicted with cancer. The present invention further relates to a method for preventing metastasis formation in a subject afflicted with cancer, comprising administering said composition to a body cavity of said subject, and thereby preventing metastasis formation in said subject. The present invention also relates to a composition and to a kit comprising a polysaccharide and a pharmaceutically acceptable means of solubilizing the same and to a device comprising a polysaccharide and means for administering the same.
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PVRIG BINDING AGENTS THAT MODULATE THE HIPPO PATHWAY AND USES THEREOF (Thu, 10 Aug 2017)
The present invention relates to agents that modulate the Hippo pathway and Hippo pathway signaling, such as antibodies, soluble receptors, polypeptides, peptides, and small molecules. The invention relates to methods of screening for and/or identifying such agents and methods of using the agents for the treatment of diseases such as cancer.
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PLANT VIRUS PARTICLES FOR DELIVERY OF PHOTOSENSITIVE AGENTS (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">Photodynamic virus particles including a plant virus particle associated with a photosensitizing agent are described. Methods of treating cancer in a subject by administering to the subject a therapeutically effective amount of the photodynamic virus particles and illuminating a cancer-bearing region of the subject to activate the photodynamic virus particles are also described.</p>
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ABIRATERONE DERIVATIVES AND NON-COVALENT COMPLEXES WITH ALBUMIN (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present disclosure provides derivatives of abiraterone, non-covalently bound complexes of the abiraterone derivatives with serum albumin, pharmaceutical compositions of the same, and methods of use thereof. The non-covalently bound complexes are significantly more water-soluble than abiraterone and are useful for the treatment of a disease or condition that can benefit from CYP17 inhibition, such as prostate cancer.</p>
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GLYCOPEPTIDE FOR CONTRAST AGENT TARGETING CANCER CELLS AND CONTRAST AGENT KIT CONTAINING THE SAME (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present disclosure relates to a glycopeptide targeting cancer cells and a contrast agent kit containing the same. The glycopeptide is one wherein an azide reporting monosaccharide is bound to a substrate peptide. As the substrate peptide is specifically cleaved by cathepsin B in cancer cells, an azide reporting monosaccharide is expressed onto the cell surface via metabolic glycoengineering, thereby providing a target for action as a contrast agent. Accordingly, because the azide is exposed to the cell surface only by cathepsin B, as it is specifically expressed in cancer cells, in particular in metastatic cancer cells, while it is limitedly expressed in normal cells and is hardly excreted out the cells, the cancer cells can be selectively imaged by an azide-specific contrast agent.</p>
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N-(4-HYDROXY-4-METHYL-CYCLOHEXYL)-4-PHENYL-BENZENESULFONAMIDES AND N-(4- HYDROXY-4-METHYL-CYCLOHEXYL)-4-(2-PYRIDYL)BENZENESULFONAMIDES AND THEIR THERAPEUTIC USE (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain substituted N-(4-hydroxy-4-methyl-cyclohexyl)-4-phenyl-benzenesulfonamide and N-(4-hydroxy-4-methyl-cyclohexyl)-4-(2-pyridyl)benzenesulfonamide compounds (collectively referred to herein as HMC compounds) that are useful, for example, in the treatment of disorders (e.g., diseases) including, inflammation and/or joint destruction and/or bone loss; disorders mediated by excessive and/or inappropriate and/or prolonged activation of the immune system; inflammatory and autoimmune disorders, for example, rheumatoid arthritis; psoriasis; psoriatic arthritis; chronic obstructive pulmonary disease (COPD); asthma; atherosclerosis; inflammatory bowel disease; ankylosing spondylitis; multiple sclerosis; systemic lupus erythematosus; Sjogren's syndrome; a disorder associated with bone loss, such as bone loss associated with excessive osteoclast activity in rheumatoid arthritis, osteoporosis, cancer-associated bone disease, or Paget's disease; cancer, such as a haematological malignancy, such as multiple myeloma, leukemia, or lymphoma, or a solid tumour cancer, such as bladder cancer, breast cancer (female and/or male), colon cancer, renal cell carcinoma, kidney cancer, lung cancer, pancreatic cancer, gastric cancer, prostate cancer, brain cancer, skin cancer, thyroid cancer, basal cell ameloblastoma, or melanoma; a disorder associated with fibrosis, such as systemic sclerosis or scleroderma; or a rare vasculitide, such as Behçet's disease. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, for example, in therapy.</p>
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ARYL ETHERS AND USES THEREOF (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present disclosure relates to HIF-2α inhibitors and methods of making and using them for treating cancer. Certain compounds were potent in HIF-2α scintillation proximity assay, luciferase assay, and VEGF ELISA assay, and led to tumor size reduction and regression in 786-O xenograft bearing mice in vivo.</p>
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ANTICANCER DRUGS INCLUDING THE CHEMICAL STRUCTURES OF AN ANDROGEN RECEPTOR LIGAND AND A HISTONE DEACETYLASE INHIBITOR (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">A novel class of drugs for treating androgen receptor (AR) positive cancer including prostate cancer and breast cancer are described. The drugs include the chemical scaffolds of a high affinity androgen receptor ligand and a histone deacetylase inhibitor. Also described are compositions including the novel drugs and methods of treating AR positive cancer using the compositions.</p>
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AMINOPYRIMIDINE DERIVATIVES FOR USE AS MODULATORS OF KINASE ACTIVITY (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The invention provides novel heterocyclic amine compounds according to Formula (I) and their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.</p>
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PYRROLIDINYL UREA, PYRROLIDINYL THIOUREA AND PYRROLIDINYL GUANIDINE COMPOUNDS AS TRKA KINASE INHIBITORS (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">Compounds of Formula I: or stereoisomers, tautomers, or pharmaceutically acceptable salts, or solvates or prodrugs thereof, where R<sup>1</sup>, R<sup>2</sup>, R<sup>a</sup>, R<sup>b</sup>, R<sup>c</sup>, R<sup>d</sup>, X, Y, B, and Ring C are as defined herein, and wherein the Y—B moiety and the NH—C(═X)—NH moiety are in the trans configuration, 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, 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="42.50mm" wi="50.97mm" file="US20170217936A1-20170803-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PYRIMIDINE-2,4-DIAMINE DERIVATIVES FOR TREATMENT OF CANCER (Fri, 04 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="24.05mm" wi="54.10mm" file="US20170217961A1-20170803-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. The compound is useful in the treatment of cancer or other diseases that may benefit from inhibition of MTH1.</p>
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NOVEL 3-AMINO-PYRROLO[3,4-C]PYRAZOLE-5(1H, 4H,6H) CARBALDEHYDE DERIVATIVES (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to compounds and pharmaceutically acceptable salts of Formulas A and B:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="92.03mm" wi="69.93mm" file="US20170217991A1-20170803-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein A, B, 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>7</sup>, R<sup>8</sup>, R<sup>9 </sup>and R<sup>10 </sup>are as defined above. The invention further relates to pharmaceutical compositions comprising the compounds and pharmaceutically acceptable salts and to methods of treating diabetes mellitus and its complications, cancer, ischemia, inflammation, central nervous system disorders, cardiovascular disease, Alzheimer's disease and dermatological disase pression, virus diseases, inflammatory disorders, or diseases in which the liver is a target organ.</p>
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GOLD(III) ANTI-CANCER AGENTS (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">A method for treating cancer and gold(III) complexes with diaminocyclohexane ligand as anticancer agents. Also described are a pharmaceutical composition incorporating the gold(III) complexes and a method of synthesizing the gold(III) complexes.</p>
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MELANOCORTIN 1 RECEPTOR LIGANDS AND METHODS OF USE (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The subject invention pertains to a modified MC1R peptide ligand comprising a peptide that is a melanocortin 1 receptor (MC1R) ligand and a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The subject invention also pertains to a MC1R peptide ligand-micelle complex comprising a peptide that is a melanocortin 1 receptor ligand connected via a click reaction product to a micelle. The micelle is stable in vivo and can target melanoma tumor cells by association of the peptide ligand with the MC1R or the tumor and selectively provide a detectable and/or therapeutic agent (such as an imageable contrast agent and/or anti-cancer agent) selectively to the tumor cell.</p>
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BOUVARDIN DERIVATIVES AND THERAPEUTIC USES THEREOF (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present invention is directed at bouvardin analogs arid related compounds for the treatment of disorders including cancer. Provided herein are bouvardin analogs and related compounds, pharmaceutical compositions and kits comprising at least one bouvardin analog or related compound, and methods for treating disorders including cancer. In some aspects the compounds inhibit translation elongation at the ribosome. The compounds are used in combination with radiation therapy or with known chemotherapeutic compositions.</p>
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INNATE IMMUNE SYSTEM MODIFICATION FOR ANTICANCER THERAPY (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to the discovery of a role of the nuclear receptor retinoid-related orphan receptor gamma (RORgamma) in tumor suppression. The introduction and expression of RORgamma result in genes activation within innate immune cells that trigger recognition and suppression of tumor cells. Thus, in various embodiments described herein, the invention encompasses a composition or a cell comprising a viral vector comprising nucleic acid sequences encoding RORgamma under the control of a neutrophil specific promoter. Additionally, the invention relates to methods of treating cancer by administering to a subject a composition that confers or increases innate immune cell anti-tumor immunity, methods for providing anti-tumor immunity in a subject, methods of stimulating innate immune response to a cell population or a tissue in a mammal and methods of diagnosing anti-tumor immunity response. Furthermore, the invention encompasses a kit for carrying out the aforementioned methods.</p>
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PROTEOLICALLY RESISTANT CYCLOTIDES WITH ANGIOTENSIN 1-7 LIKE ACTIVITY (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">Described herein is a novel cyclotide able to activate the unique receptor of angiotensin-(1-7) (AT1-7), the MAS1 receptor. This cyclotide may be used in the treatment of cancer and myocardial infarction.</p>
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Wnt Antagonists and Methods of Treatment and Screening (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to compositions comprising Wnt antagonists and methods of treating Wnt-associated diseases and disorders, such as cancer, inducing differentiation, and reducing the frequency of cancer stem cells, as well as novel methods of screening for such Wnt antagonists. In particular, the invention discloses soluble FZD, SFRP and Ror receptors and their use.</p>
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ARYL ETHERS AND USES THEREOF (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present disclosure relates to HIF-2α inhibitors and methods of making and using them for treating cancer. Certain compounds were potent in HIF-2α scintillation proximity assay, luciferase assay, and VEGF ELISA assay, and led to tumor size reduction and regression in 786-O xenograft bearing mice in vivo.</p>
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Novel Triarylethylene Compounds and Methods Using Same (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">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.</p>
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SUBSTITUTED BENZENE AND 6,5-FUSED BICYCLIC HETEROARYL COMPOUNDS (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to substituted benzene compounds and bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.</p>
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NOVEL PYRAZOLO[3,4-d]PYRIMIDINE COMPOUND OR SALT THEREOF (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">To provide a novel compound having a HER2 inhibitory effect and having a cytostatic effect. It is also intended to provide a medicament useful in the prevention and/or treatment of a disease involving HER2, particularly, cancer, on the basis of the HER2 inhibitory effect.</p> <p id="p-0002" num="0000">The present invention provides a compound of formula (I) wherein X, Y, Z<sub>1</sub>, Z<sub>2</sub>, Z<sub>3</sub>, Z<sub>4</sub>, W, n, R<sub>1</sub>, R<sub>2</sub>, and R<sub>3 </sub>have meanings as defined in the present specification, or a salt thereof.</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="65.70mm" wi="69.85mm" file="US20170217970A1-20170803-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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TRICYCLIC HETEROCYCLES AS BET PROTEIN INHIBITORS (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to tricyclic heterocycles which are inhibitors of BET proteins such as BRD2, BRD3, BRD4, and BRD-t and are useful in the treatment of diseases such as cancer.</p>
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ANTI-cMET ANTIBODY (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The invention relates to a novel antibody capable of binding specifically to the human c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor, with an improved antagonistic activity, said antibody comprising a modified hinge region.</p> <p id="p-0002" num="0000">The invention also relates to a composition comprising such an antibody antagonist to c-Met and its use as a medicament for treating cancer.</p>
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Salivary Transcriptomics and Proteomic Biomarkers for Breast Cancer Detection (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">Presented herein are biomarkers related to breast cancer. The presently identified salivary biomarkers create the basis for a breast cancer detection bioassay with sensitivity and specificity. Means and methods for evaluating the data generated using multiple biomarkers in order to validate findings and further use of the multiplexed breast cancer assay in clinical, diagnostic and therapeutic uses is also included.</p>
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ALDOSE REDUCTASE INHIBITORS AND USES THEREOF (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to novel compounds and pharmaceutical compositions thereof, and methods for promoting healthy aging of skin, the treatment of skin disorders, the treatment of cardiovascular disorders, the treatment of renal disorders, the treatment of angiogenesis disorders, such as cancer, treatment of tissue damage, such as non-cardiac tissue damage, the treatment of evolving myocardial infarction, and the treatment of various other disorders, such as complications arising from diabetes with the compounds and compositions of the invention. Other disorders can include, but are not limited to, atherosclerosis, coronary artery disease, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, infections of the skin, peripheral vascular disease, stroke, and the like.</p>
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THIENOPYRIMIDINE DERIVATIVES, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM (Fri, 04 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="43.10mm" wi="62.15mm" file="US20170216293A1-20170803-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sub>1</sub>, R<sub>2</sub>, R<sub>3</sub>, R<sub>4</sub>, R<sub>5</sub>, R<sub>6</sub>, R<sub>7</sub>, R<sub>12</sub>, X, A and n are as defined in the description.</p> <p id="p-0004" num="0000">Medicinal products containing the same which are useful in treating pathologies involving a deficit in apoptosis, such as cancer, auto-immune diseases, and diseases of the immune system.</p>
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SALTS OF HETEROCYCLIC MODULATORS OF HIF ACTIVITY FOR TREATMENT OF DISEASE (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present disclosure relates to salts of heterocyclic compounds and methods that inhibit HIF pathway activity. The compounds are designed to treat or prevent cancer and other hypoxia-mediated diseases.</p>
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ALDOSE REDUCTASE INHIBITORS AND USES THEREOF (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to novel compounds and pharmaceutical compositions thereof, and methods for promoting healthy aging of skin, the treatment of skin disorders, the treatment of cardiovascular disorders, the treatment of renal disorders, the treatment of angiogenesis disorders, such as cancer, treatment of tissue damage, such as non-cardiac tissue damage, the treatment of evolving myocardial infarction, and the treatment of various other disorders, such as complications arising from diabetes with the compounds and compositions of the invention. Other disorders can include, but are not limited to, atherosclerosis, coronary artery disease, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, infections of the skin, peripheral vascular disease, stroke, and the like.</p>
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3-(3H-IMIDAZO[4,5-C]PYRIDIN-2-YL)-1H-PYRAZOLO[3,4-C]PYRIDINE AND THERAPEUTIC USES THEREOF (Fri, 04 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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NANOPARTICLE MODIFICATION OF HUMAN ADIPOSE-DERIVED MESENCHYMAL STEM CELLS FOR TREATING BRAIN CANCER AND OTHER NEUROLOGICAL DISEASES (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The presently disclosed subject matter provides compositions, methods, and kits for transfecting adipose-derived mesenchymal stem cells (AMSCs) in freshly extracted adipose tissue using nanoparticles comprising biodegradable polymers self-assembled with nucleic acid molecules. The presently disclosed subject matter also provides methods for treating a neurological disease in a patient in need thereof, the method comprising administering the AMSCs transfected with the nucleic acid molecules to the patient, wherein the nucleic acid molecules encode one or more bioactive molecules functional in the treatment of a neurological disease, particularly wherein the neurological disease is a brain tumor.</p>
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Oncolytic Herpes Simplex Virus And Therapeutic Uses Thereof (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to variants of herpes simplex virus (HSV) that selectively infect and replicate in cancer cells, including HSV strains that selectively infect and replicate in bladder cancer cells. Preferred HSV of the invention have intact endogenous Us11 and Us12 genes and have genes encoding ICP34.5 replaced with a gene encoding Us11 fused to an HSV immediate early (IE) promoter. The variant HSV of the invention also comprise one or more additional heterologous genes encoding immunomodulatory polypeptides. Methods and compositions using these variant HSV, e.g., for treating cancer in a subject, are also provided.</p>
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COMPOSITIONS AND METHODS FOR SENSITIZING LOW RESPONSIVE TUMORS TO CANCER THERAPY (Fri, 04 Aug 2017)
The present invention discloses compositions and methods for selectively delivering apoptosis inducing agents (referred to as 'apoptogens') to the tumor prior to conventional therapeutic treatment protocol. We refer to this technology as 'a priori activation of apoptosis pathways of tumors (AAAPT). Specifically, the present invention relates to an ensemble (or 'bioconjugate') comprising of an apoptogen (A) and a tumor targeting group (or vector) (T), wherein the apoptogen is either connected directly to the targeting group or optionally attached through an intervening linker (L). Thus, a AAAPT bioconjugate bearing a linker is capable of being cleaved by enzymes and is expected to induce much higher death of tumor cells compared to normal cells. The AAAPT conjugates of the present invention induce large synergistic and selective cancer cell death response in combination with therapeutic agents.
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METHODS AND COMPOSITIONS FOR PREDICTING A COLON CANCER SUBTYPE (Fri, 04 Aug 2017)
Disclosed herein are methods for identifying a genetic susceptibility to colon cancer in as subject, the method comprising determining the mRNA expression level of one or more of FSCN1, ZIC2, ZIC5, CRYBA2, MUC6, TRNP1 and SEMG1 in a colon tissue sample in the subject, where a ratio of the sample expression level of one or more genes in the panel to a reference expression level of one or more genes in the panel indicates cancer or and increased susceptibility of cancer. Disclosed herein are diagnostic devices comprising one or more biomarkers, wherein the biomarkers are FSCN1, ZIC2, ZIC5, CRYBA2, MUC6, TRNP1 and SEMG1; and a gene expression panel consisting of primers or probes for detecting FSCN1, ZIC2, ZIC5, CRYBA2, JMUC6, TRNP1 and SEMG1 in a sample, and methods for assessing risk of developing colon cancer in a subject.
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HETEROCYCLIC COMPOUNDS AS INHIBITORS OF CLASS I PI3KS (Fri, 04 Aug 2017)
The present application discloses a novel class of heterocycles as class I P13Ks inhibitors. The compounds claimed herein could be used alone or in combination therapies for the treatment of a wide range of disorders such as autoimmune, inflammatory and allergic diseases, asthma, COPD, parasitic infections, diabetes, and cancer.
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METHODS FOR TREATING BRAIN METASTASES USING COMBINATIONS OF ANTI-P13K AND ANTI-mTOR AGENTS (Fri, 04 Aug 2017)
The present invention relates to methods of treating brain metastases using synergistic combinations of anti-PI3K and anti-mTOR therapies. It has also been determined that blocking PI3K and mTOR provides therapeutic benefit for treating brain metastases.
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METHODS FOR PREPARING ANTIBODIES WITH A DEFINED GLYCOSYLATION PATTERN (Fri, 04 Aug 2017)
The present disclosure relates to a process for preparing antibodies with a defined glycosylation pattern, in particular antibodies with a glycan terminating in an N-acetylglucosamine. The antibodies of the disclosure are suitable for use in a process to conjugate a payload thereto. The disclosure also extends to molecules obtained and obtainable from the process disclosed herein, novel molecules and intermediates, compositions comprising said molecules and uses of the molecules and compositions, particularly in treatment, for example in the treatment of cancer.
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DNA ALKYLATION AND CROSS-LINKING AGENTS AS COMPOUNDS AND PAYLOADS FOR TARGETED THERAPIES (Fri, 04 Aug 2017)
The present invention is directed to compounds related to precolibactin, pharmaceutical compositions based upon these compounds and methods of synthesis which are employed to provide intermediates and final compounds, which are principally alkylating agents and anticancer compounds. The chemical synthetic approach disclosed facilitates the synthesis of numerous precolibactin analogs which can be used in the treatment of cancer.
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BENZIMIDAZOLE COMPOUNDS, USE AS INHIBITORS OF WNT SIGNALING PATHWAY IN CANCERS, AND METHODS FOR PREPARATION THEREOF (Fri, 04 Aug 2017)
The present disclosure is concerned with benzimidazole compounds that are capable of inhibiting Wnt signaling and methods of treating disease states such as, for example, cancer, using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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TRIAZOLE DERIVATIVES OF MELAMPOMAGNOLIDE B AND METHODS OF USE THEREOF (Fri, 04 Aug 2017)
The present disclosure relates to triazole derivatives of melampomagnolide B, their synthesis, and their use as anti-cancer compounds.
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ANTI-CEACAM5 ANTIBODIES AND USES THEREOF (Thu, 03 Aug 2017)
The present disclosure describes antibodies which bind human and Macaca fascicularis CEACAM5 proteins, as well as isolated nucleic acids, vectors and host cells comprising a sequence encoding said antibodies. The disclosure also provides immunoconjugates comprising said antibodies conjugated or linked to a growth-inhibitory agent, and to pharmaceutical compositions comprising antibodies, or immunoconjugates of the disclosure . The antibodies or immunoconjugates of the disclosure are used for the treatment of cancer or for diagnostic purposes.
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Compounds (Wed, 02 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="52.66mm" wi="75.69mm" file="US09718848-20170801-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> 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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Isoxazole compounds as inhibitors of heat shock proteins (Wed, 02 Aug 2017)
<p id="p-0001" num="0000">Isoxazoles of formula (A) or (B) are inhibitors of HSP90 activity, and useful for treatment of, for example cancers:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="42.59mm" wi="69.85mm" file="US09718793-20170801-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein R<sub>1</sub>, is a group of formula (IA): —Ar<sup>1</sup>-(Alk<sup>1</sup>)<sub>p</sub>-(Z)<sub>r</sub>-(Alk<sup>2</sup>)<sub>s</sub>-Q, wherein in any compatible combination Ar<sup>1 </sup>is an optionally substituted aryl or heteroaryl radical, Alk<sup>1 </sup>and Alk<sup>2 </sup>are optionally substituted divalent C<sub>1</sub>-C<sub>6 </sub>alkylene or C<sub>2</sub>-C<sub>6 </sub>alkenylene radicals, p, r and s are independently 0 or 1, Z is —O—, —S—, —(C═O)—, —(C═S)—, —SO.sub.2-, —C(═O)O—, —C(═O)NR<sup>A</sup>—, —C(═S)NR<sup>A</sup>—, —SO<sub>2</sub>NR<sup>A</sup>—, —NR<sup>A</sup>C(═O)—, —NR<sup>A</sup>SO<sub>2</sub>— or —NR<sup>A</sup>— wherein R<sup>A </sup>is hydrogen or C<sub>1</sub>-C<sub>6 </sub>alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R<sub>2 </sub>is (i) a group of formula (IA) above or (ii) a carboxamide radical; or (iii) a non aromatic carbocyclic or heterocyclic ring wherein a ring carbon is optionally substituted, and/or a ring nitrogen is optionally substituted by a group of formula -(Alk<sup>1</sup>)p-(Z)<sub>r</sub>-(Alk<sup>2</sup>)<sub>s</sub>-Q wherein Q, Alk<sup>1</sup>, Alk<sup>2</sup>, Z, p, r and s are as defined above in relation to group (IA); and R<sub>3 </sub>is hydrogen, optionally substituted cycloalkyl, cycloalkenyl, C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>alkenyl, or C<sub>1</sub>-C<sub>6 </sub>alkynyl; or a carboxyl, carboxamide, or carboxyl ester group. </p>
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METHODS OF TREATING CANCER AND PREVENTING CANCER DRUG RESISTANCE (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">Provided herein are methods of using antagonists of G9a, for example, for treating cancer and/or preventing drug resistance in an individual. For example, a method of treating cancer in an individual comprising administering to the individual an antagonist of G9a alone or in combination with a cancer therapy agent is provided. In some embodiments, the antagonist of G9a increases the period of cancer sensitivity and/or delays development of cancer resistance.</p>
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Compositions, methods and kits for treating complement related disorders (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">Compositions, methods and kits are provided for treating complement related disorders in a subject with protein in combination having protein fusions of at least two of a CD46 protein, a CD55 protein and a CD59 protein or with a recombinant chimeric protein having at least two of a CD46 protein, a CD55 protein and a CD59 protein or with nucleic acids encoding these proteins. The composition negatively modulates classical and alternative complement pathways thereby treating complement related disorder such as macular degeneration, age-related macular degeneration, diabetic retinopathy, inflammatory bowel disease, thyroiditis, cryoglobulinaemia, fetal loss, organ graft rejection, cancer, etc.</p>
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GLUTAMINASE INHIBITOR DISCOVERY AND NANOPARTICLE-ENHANCED DELIVERY FOR CANCER THERAPY (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">Currently available glutaminase inhibitors are generally poorly soluble, metabolically unstable, and/or require high doses, which together reduce their efficacy and therapeutic index. These can be formulated into nanoparticles and delivered safely and effectively for treatment of pancreatic cancer and other glutamine addicted cancers. Studies demonstrate that nanoparticle delivery of BPTES, relative to use of BPTES alone, can be safely administered and provides dramatically improved tumor drug exposure, resulting in greater efficacy. GLS inhibitors can be administered in higher concentrations with sub-100 nm nanoparticles, since the nanoparticles package the drug into “soluble” colloidal nanoparticles, and the nanoparticles deliver higher drug exposure selectively to the tumors due to the enhanced permeability and retention (EPR) effect. These factors result in sustained drug levels above the IC50 within the tumors for days, providing significantly enhanced efficacy compared to unencapsulated drug.</p>
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DEUTERO-PHENFORMIN DERIVATIVES (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">The present disclosure is directed to novel phenformin derivatives, and their pharmaceutically acceptable salts, solvates, or stereoisomers thereof. This disclosure also provides compositions and the use of such compositions in method of treating cancer, diabetes, or polycystic ovarian syndrome.</p>
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SUBSTITUTED THIOXANTHENONE AUTOPHAGY INHIBITORS (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">Autophagy inhibitors useful for the treatment of cancer and other diseases are described. The autophagy inhibitors are a compound of formula: I wherein R<sup>1 </sup>is a group selected from lower alkyl, lower alkyl amide, lower alkyl ester, lower alkyl ketone, and lower alkyl ether; R<sup>2 </sup>and R<sup>3 </sup>are H or a group selected from cycloalkyl, lower alkyl, lower alkyl amide, lower alkyl ester, lower alkyl ketone, and lower alkyl ether; R<sup>4 </sup>is a heteroaryl group; and L is a —(CH<sub>2</sub>)<sub>n</sub>—X—(CH<sub>2</sub>)<sub>n</sub>— group, wherein n is 1, 2, 3, or 4, X is absent, O, S, or N—R<sup>5</sup>, wherein R<sup>5 </sup>is H or a lower alkyl group, 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="30.56mm" wi="59.86mm" file="US20170210746A1-20170727-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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TRICYCLIC HETEROCYCLES AS BET PROTEIN INHIBITORS (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to tricyclic heterocycles which are inhibitors of BET proteins such as BRD2, BRD3, BRD4, and BRD-t and are useful in the treatment of diseases such as cancer.</p>
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METHODS AND SYSTEMS FOR PROCESSING PARTICLES (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">Described herein are improved microfluidic devices and methods for processing cells that can improve cell quality, streamline workflows, and lower costs. Applications include research and clinical diagnostics in cancer, infectious disease, and inflammatory disease, among other disease areas.</p>
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METHOD OF TREATING HER2-POSITIVE BREAST CANCERS WITH SELECTIVE ANDROGEN RECEPTOR MODULATORS (SARMS) (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">This invention relates to the treatment of breast cancer in a subject, for example a female subject. Including methods of: treating metastatic breast cancer; refractory breast cancer; AR-positive breast cancer; AR-positive refractory breast cancer; AR-positive metastatic breast cancer; AR-positive and ER-positive breast cancer; triple negative breast cancer; advanced breast cancer; breast cancer that has failed SERM (tamoxifen, toremifene), aromatase inhibitor, palbociclib (Ibrance), trastuzumab (Herceptin, ado-trastuzumab emtansine), pertuzumab (Perjeta), lapatinib, exemestane (Aromasin), bevacizumab (Avastin), and/or fulvestrant treatments; metastasis in a subject suffering from breast cancer; and/or HER2-positive; comprising administering to the subject a therapeutically effective amount of a selective androgen receptor modulator (SARM) compound.</p>
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HETEROCYCLIC COMPOUND (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">Provided is a compound useful for the prophylaxis or treatment of cancer.</p> <p id="p-0002" num="0000">The present invention relates to a compound represented by formula (I):</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.99mm" wi="69.85mm" file="US20170209452A1-20170727-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">wherein each symbol in the formula is as defined in the specification, or a salt thereof or a prodrug thereof, which is useful for the prophylaxis or treatment of cancer.</p>
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SMALL MOLECULE CANCER TREATMENTS THAT CAUSE NECROSIS IN CANCER CELLS BUT DO NOT AFFECT NORMAL CELLS (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">A method of treating cancer in a subject, including: providing a subject having a plurality of cancer cells; and administering to the subject, a therapeutically effective amount of a composition including: an HDM-2 binding component; and a membrane resident component, the membrane resident component bound to the HDM-2 binding component. Also provided are a method of selectively necrosing cancer cells, a method of causing membranolysis in cancer cells, and a cancer treatment composition.</p>
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ITRACONAZOLE ANALOGUES AND METHODS OF USE THEREOF (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">Disclosed herein are analogues of itraconazole that are both angiogenesis and hedgehog signaling pathway inhibitors. The compounds are expected to be useful in the treatment of cancer, particularly cancers that are dependent upon the hedgehog signaling pathway such as basal cell carcinoma and medulloblastoma.</p>
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PYRIDINYLAMINOPYRIMIDINE DERIVATIVES, PREPARATION PROCESS AND USE THEREOF (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to pyridinylaminopyrimidine derivatives represented by the following formula (I), and pharmaceutically acceptable salts, preparation process and use thereof, wherein R<sub>1</sub>, R<sub>2</sub>, R<sub>3</sub>, R<sub>4</sub>, R<sub>5</sub>, m and A are defined as in the description. Pyridinylaminopyrimidine derivatives of the present invention can selectively inhibit the activity of mutant-type epidermal growth factor receptor (EGFR), have a good inhibition for the cancer cell proliferation, and therefore can be used as a therapeutic agent for treating tumors and relevant diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.65mm" wi="69.77mm" file="US20170210739A1-20170727-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Benzimidazole Compounds, Use As Inhibitors of WNT Signaling Pathway in Cancers, and Methods for Preparation Thereof (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">The present disclosure is concerned with benzimidazole compounds that are capable of inhibiting Wnt signaling and methods of treating disease states such as, for example, cancer, using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.</p>
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NOVEL HDAC6 INHIBITORS AND THEIR USES (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to small molecule compounds and their use as HDAC inhibitors and in the treatment of various diseases, such as cancer. The present invention further relates to methods of synthesizing the compounds and methods of treatment. H-L(HA), H is a head group selected from (head group 1), (head group 2), (head group 3), (head group 4), (head group 5) and (head group 6).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="244.52mm" wi="76.20mm" file="US20170210743A1-20170727-C00001.TIF" alt="text missing or illegible when filed" img-content="chem" img-format="tif"/> </chemistry> </p>
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9H-PYRIMIDO [4,5-B]INDOLES AND RELATED ANALOGS AS BET BROMODOMAIN INHIBITORS (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">The present disclosure provides substituted 9H-pyrimido[4,5-b]indoles and 5H-pyrido[4,3-b]indoles and related analogs represented by Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.42mm" wi="69.85mm" file="US20170210761A1-20170727-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R<sup>1a</sup>, A, B<sup>1</sup>, B<sup>2</sup>, G, X<sup>1</sup>, Y<sup>1</sup>, Y<sup>2</sup>, and Y<sup>3 </sup>are as defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a condition or disorder responsive to inhibition of BET bromodomains. Compounds of the present disclosure are especially useful for treating cancer.</p>
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TH-302 SOLID FORMS AND METHODS RELATED THERETO (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">The present invention provides a new method for making TH-302 and solid forms thereof. The compound in its solid form is an effective anti-cancer agent and may be used in various pharmaceutical compositions, and are particularly effective for the treatment of cancer. The invention also provides a method for preparing such compounds and forms and for treating cancer in a mammal comprising the step of administering a therapeutically effective amount of a solid form of TH-302 thereof.</p>
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COMPOSITIONS AND METHODS FOR DIAGNOSIS AND TREATMENT OF HEPATIC CANCERS (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to methods of treating liver cancer using a Notch signaling inhibitor. Compositions and methods for the treatment of liver cancers are also provided.</p>
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(E)-4-(4-ACRYLAMIDOPHENOXY)-N-METHYLPICOLINAMIDE CONJUGATES AS POTENTIAL ANTICANCER AGENTS (Fri, 28 Jul 2017)
The present invention relates to a compound of formula A useful as potential anticancer agents against human cancer cell lines and process for the preparation thereof.
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N-((1-PHENYL-9H-PYRIDO[3,4-B]INDOL-3-YL)METHYL)CINNAMAMIDES AS ANTICANCER AGENTS AND PREPARATION THEREOF (Fri, 28 Jul 2017)
A compound of general formula A, useful as potential anticancer agents against human cancer cell lines and process for the preparation threof. General formula A R1 = 3-F, 3,4,5-OMe, 4-OMe, H, 4-CF3, 4-Cl, 4-OH-3-OMe, 3,4-CH2-O-CH2, 3,5-F, 4-OH, 1-napthyl, 9-phenanthryl, 4-Me. R2 = 3,4,5-OMe, 3,4-Cl, 4-F, 3,5-F, 2,5-OMe, 4-Cl, 4-OH-3-OMe, 3-OH, 3,4,5-OH, 4-CF3, 4-OMe, 4-NH2
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NOVEL MOLECULE WITH ANTI-CANCER ACTIVITY (Fri, 28 Jul 2017)
The present invention provides a new compound of formula (I): extracted from a seaweed, and its use for inhibiting the growth of cancer cells, as well as methods for its extraction and isolation.
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NEW SUBSTITUTED CYANOINDOLINE DERIVATIVES AS NIK INHIBITORS (Fri, 28 Jul 2017)
The present invention relates to pharmaceutical agents of formula (I) useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF- KB-inducing kinase (NIK - also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.
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NEW 6-MEMBERED HETEROAROMATIC SUBSTITUTED CYANOINDOLINE DERIVATIVES AS NIK INHIBITORS (Fri, 28 Jul 2017)
The present invention relates to pharmaceutical agents of formula (I), useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-KB-inducing kinase (NIK - also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.
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METHODS FOR TREATING CANCER WITH RORGAMMA INHIBITORS (Fri, 28 Jul 2017)
The present invention provides compositions, methods, and kits comprising one or more compounds of Formula I, such as XY018, alone or in combination with one or more anticancer drugs, such as an anti-androgen drug, that are useful for treating cancer, e.g., prostate cancer, such as castration-resistant prostate cancer (CRPC), and numerous other types of cancer including lung cancer, breast cancer, liver cancer, ovarian cancer, endometrial cancer, bladder cancer, colon cancer, gastric cancer, lymphoma, and glioma.
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IRAK4 INHIBITING AGENTS (Fri, 28 Jul 2017)
Provided are compounds of Formula I, or pharmaceutically acceptable salts thereof, and methods for their use and production. Formula (I) The compounds are IRAK-4 inhibitors useful for treating an inflammatory disease, an autoimmune disease, cancer, a cardiovascular disease, a disease of the central nervous system, a disease of the skin, an ophthalmic disease and condition, and a bone disease.
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PYRIMIDINE COMPOUNDS INHIBITING THE FORMATION OF NITRIC OXIDE AND PROSTAGLANDIN E2, METHOD OF PRODUCTION THEREOF AND USE THEREOF (Thu, 27 Jul 2017)
The invention provides pyrimidine compounds of general formula (I), which reduce simultaneously the production of nitric oxide (NO) and prostaglandin E2 (PGE2). They have no negative effect on the viability of cells in concentrations decreasing the production of these factors by up to 50%; they are not cytotoxic. Furthermore, a method of preparation of the pyrimidine compounds of general formula (I), carrying 2-formamido group, a pharmaceutical composition comprising the substituted pyrimidine compounds according to the invention, and the use of these compounds for the treatment of inflammatory and cancer diseases are provided.
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INDOLE DERIVATIVES FOR THE PREVENTION AND/OR TREATMENT OF DIABETES AND ASSOCIATED METABOLIC DISORDERS (Thu, 27 Jul 2017)
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.
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HETEROCYCLYLAMINES AS PI3K INHIBITORS (Thu, 27 Jul 2017)
The present invention provides heterocyclylamine derivatives of Formula I: wherein the variables are defined herein, that modulate the activity of phosphoinositide 3-kinases (PI3Ks) and are useful in the treatment of diseases related to the activity of PI3Ks including, for example, inflammatory disorders, immune-based disorders, cancer, and other diseases.
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COMPOUNDS FOR THE TREATMENT OF CANCER AND INFLAMMATORY DISEASES (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to novel compounds and pharmaceutical compositions thereof which may be useful in the treatment and/or prevention of various conditions. The present invention also provides methods of preparing such compounds and compositions, and methods of using the same.</p>
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CONJUGATES FOR IMMUNOTHERAPY (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">The current invention pertains to a molecular conjugate comprising an antagonist of a cell surface receptor specific to a target cell and an immune effector, such as a T cell modulator, conjugated to the antagonist. The target cell can be a cell responsible for development of a disease in a subject, for example, a cancer cell. In certain embodiments, the immune effector is an immune effector protein or an immune effector fragment thereof. The current invention also pertains to a method of treating a disease in a subject, the method comprising administering to the subject a pharmaceutically effective amount of the molecular conjugates of the current invention to the subject. The methods of the current invention can be used to treat cancer, such as breast cancer, ovarian cancer, prostate cancer, lung cancer, pancreatic cancer, or melanoma.</p>
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Hyaluronic Acid-Based Nanoparticles as Biosensors for Imaging-Guided Surgery and Drug Delivery Vehicles and Methods Associated Therewith (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to intraoperative fluorescent imaging (IFI) used both pre-clinically using in-vivo models, as well as clinically to map sentinel lymph nodes in breast cancer, skin cancer, GI cancer, lung cancer, prostate cancer and several other cancers. IFI can be used to image solid tumors both non-specifically in hepatobiliary and breast cancers as well as in prostate and ovarian cancer. In one embodiment, two-dimensional resolution to 10 μm<sup>2 </sup>is possible with optical imaging, significantly higher than other imaging modalities.</p> <p id="p-0002" num="0000">In one embodiment, the present invention relates to a series of self-assembled nanoparticles using HLA (hyaluronic acid) as both a polymeric backbone as well as targeting ligand. In some embodiments, the present invention relates to the synthesis of HLA conjugates, and the effect of variation of the hydrophobic ligand structure and conjugation level on nanoparticle self-assembly, size, ICG loading efficiency, and ICG fluorescence quenching and reactivation.</p>
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IMIDAZOLYL KINASE INHIBITORS AND USES THEREOF (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">The present disclosure provides imidazolyl compounds of Formula (I) and methods of preparing the compounds. The provided compounds are able to bind protein kinases and may be useful in modulating (e.g., inhibiting) the activity of a protein kinase in a subject or cell and/or in treating or preventing a disease (e.g., proliferative disease, genetic disease, hematological disease, neurological disease, painful condition, psychiatric disorder, or metabolic disorder) in a subject in need thereof. Also provided are pharmaceutical compositions, kits, methods, and uses that include or involve a compound described herein.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.40mm" wi="67.39mm" file="US20170204082A1-20170720-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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DEOXYCYTIDINE KINASE INHIBITORS (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">Provided herein are compounds that bind to dCK and methods for treating cancer.</p>
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NOVEL COMPOUNDS USEFUL AS S100-INHIBITORS (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">A compound of formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutical composition comprising the compound. The compound is an inhibitor of interactions between S100A9 and interaction partners such as RAGE, TLR4 and EMMPRIN and as such is useful in the treatment of disorders such as cancer, autoimmune disorders, inflammatory disorders and neurodegenerative disorders.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.41mm" wi="63.58mm" file="US20170204098A1-20170720-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Chemical Compounds (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">The present disclosure concerns compounds of Formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.29mm" wi="69.85mm" file="US20170204100A1-20170720-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically-acceptable salts thereof, wherein R<sup>1</sup>, R<sup>2 </sup>and R<sup>3 </sup>have any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cancer.</p>
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PROCESSES FOR PREPARING (R)-1-(5-CHLORO-[1,1`-BIPHENYL]-2-YL)-2,2,2-TRIFLUOROETHANOL AND 1-(5-CHLORO-[1,1`-BIPHENYL]-2-YL)-2,2,2-TRIFLUOROETHANONE (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to processes for the preparation of (R)-1-(5-chloro-[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroethanol, 1-(5-chloro-[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroethanone, and intermediates thereof, which are useful in the preparation of inhibitors of TPH1 for the treatment of, for example, gastrointestinal, cardiovascular, pulmonary, inflammatory, metabolic, low bone mass diseases, serotonin syndrome, and cancer.</p>
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APIGENIN ANALOGS, COMPOSITIONS, AND METHODS RELATED THERETO (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">Certain embodiments are directed to apigenin analogues or derivatives. In certain aspects, the derivatives are developed as cystathionine-beta-synthase (CBS) inhibitors. In certain aspects, the derivatives are used as anticancer or anti-inflammatory agents. Certain embodiments are directed methods of treating or compositions used to treat fibrosis and cancers. In certain aspects one or more compounds described herein can be administered to a subject to treat pancreatic fibrosis, liver fibrosis, pancreatic cancer, colon cancer, breast cancer, brain tumors, head/neck cancer, prostate and lung cancers as well as other inflammation.</p>
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ANTI-CANCER COMPOUNDS TARGETING RAL GTPASES AND METHODS OF USING THE SAME (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">Methods of inhibiting the growth or metastasis of a cancer in a subject by inhibiting a Ral GTPase in the subject, and small molecule inhibitors of Ral GTPases useful in the methods of the invention. Pharmaceutical compositions containing the compounds of the invention, and methods of using the same.</p>
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MACROCYCLIC KINASE INHIBITORS AND USES THEREOF (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">The present disclosure provides macrocyclic compounds of Formula (I). The provided compounds are able to bind protein kinases and may be useful in modulating (e.g., inhibiting) the activity of a protein kinase in a subject or cell and/or in treating or preventing a disease (e.g., proliferative disease, genetic disease, hematological disease, neurological disease, painful condition, psychiatric disorder, or metabolic disorder) in a subject in need thereof. Also provided are pharmaceutical compositions, kits, methods, and uses that include or involve a compound described herein.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="40.89mm" wi="72.73mm" file="US20170204116A1-20170720-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PYRROLE COMPOUNDS, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">Compounds of formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="52.32mm" wi="69.85mm" file="US20170202851A1-20170720-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein A<sub>1</sub>, A<sub>2</sub>, R<sub>a</sub>, R<sub>b</sub>, R<sub>c</sub>, R<sub>d</sub>, R<sub>3</sub>, R<sub>4</sub>, R<sub>5 </sub>and T are as defined in the description. Medicinal products containing the same which are useful in treating pathologies involving a deficit in apoptosis, such as cancer, auto-immune diseases, and diseases of the immune system.</p>
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SMALL MOLECULE INHIBITORS OF STAT3 WITH ANTI-TUMOR ACTIVITY (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">The present invention concerns compounds, compositions containing these compounds, and methods of using these compounds and compositions as inhibitors of Stat3 signaling, Stat3 dimerization, Stat3-DNA binding, Stat5-DNA binding, and/or aberrant cell growth in vitro or in vivo, e.g., as anti-cancer agents for treatment of cancer, such as breast cancer. The compounds of the invention include, but are not limited to, NSC 74859 (S3I-201), NSC 42067, NSC 59263, NSC 75912, NSC 11421, NSC 91529, NSC 263435, and pharmaceutically acceptable salts and analogs of the foregoing. Other non-malignant diseases characterized by proliferation of cells that may be treated using the compounds of the invention, but are not limited to, cirrhosis of the liver; graft rejection; restenosis; and disorders characterized by a proliferation of T cells such as autoimmune diseases, e.g., type 1 diabetes, lupus and multiple sclerosis. The invention further includes an in-vitro screening test for the presence of malignant cells in a mammalian tissue; a method of identifying inhibitors of constitutive Stat3 activation, Stat3-DNA binding, Stat5-DNA binding, and/or Stat3 dimerization; and a method of identifying anti-cancer agents.</p>
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METHODS OF TREATING AND PREVENTING CANCER DRUG RESISTANCE (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">Provided herein are combination therapies for the treatment of pathological conditions, such as cancer, using an antagonist of FGFR signaling and a B-raf antagonist.</p>
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METHOD FOR PRODUCING MYCOSPORINE-LIKE AMINO ACID USING MICROBES (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">Provided are: a method for producing a mycrosporine-like amino acid (MAA) that includes a step in which microbes are cultivated that produce MAA on the outside of bacterial cells, a step in which the bacterial cells and extracellular culture fluid are separated, and a step in which the MAA is recovered from the extracellular culture fluid; an MAA indicated by formula (1), an MAA produced using this method, or an ultraviolet-absorbing composition including the MAA indicated by formula (1); and a composition including the MAA produced using this method or the MAA indicated by formula (1), for preventing at least one symptom or disease selected from a group comprising acute skin reactions, aging of the skin, and skin cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.94mm" wi="60.71mm" file="US20170202762A1-20170720-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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SELF-ASSEMBLING VERTEPORFIN AMPHIPHILES (SAVA) FOR LOCAL CANCER THERAPY (Fri, 21 Jul 2017)
The present invention provides compositions comprising Verteporfin and other anticancer compounds linked to a hydrophilic peptide through a degradable linker molecule to allow the anticancer compounds to penetrate tissues via in situ administration. The compounds of the present invention are useful for sensitizing tumor cells to radiotherapy, preventing recurrence of tumors after surgical resection and for treating remaining unremoved cancer cells at the site of the tumor.
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INHIBITING B-CELL LYMPHOMA 2 (BCL-2) AND RELATED PROTEINS (Fri, 21 Jul 2017)
Novel compounds inhibiting anti-apoptosis proteins B-cell lymphoma 2 (Bcl-2) and Bcl-XL include compounds of formula (I) and formula (II) disclosed herein, as well as liposome compositions comprising Bcl-2 inhibitor compounds. These compositions are useful for the treatment of cancer.
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CYCLIC DINUCLEOTIDES FOR TREATING CONDITIONS ASSOCIATED WITH STING ACTIVITY SUCH AS CANCER (Fri, 21 Jul 2017)
This disclosure features dinucleotide compounds that modulate Stimulator of Interferon Genes (STING) activity, for use for example in the treatment of cancer. This disclosure also features compositions as well as other methods of using and making the same (Fomula (A)). A and B are each independently selected from the group consisting of Formulae (i), (ii), (iii), and (iv).
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METHODS OF TREATING DISEASE BY METABOLIC CONTROL OF T-CELL DIFFERENTIATION (Fri, 21 Jul 2017)
Provided herein are methods for treating an individual for a disease (e.g., an autoimmune disease or a cancer) using an active agent which affects metabolism of α-ketoglutarate (α-KG) and/or 2-hydroxyglutarate (2-HG) in differentiating T cells. In some embodiments, a Got1 inhibitor is used to generate a population of T cells enriched in peripheral regulatory T (iTreg) cells, which population enriched in iTreg cells may find use in treating an autoimmune disease. In some embodiments, a TCA cycle-associated metabolite, or a derivative thereof, is used to generate a population of T cells in enriched in IL-17- and IL-17F-producing CD4 T (TH17) cells, which population enriched in TH17 cells may find use in treating a cancer.
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COMPOUNDS FOR INHIBITING CANCER AND VIRUS (Fri, 21 Jul 2017)
The invention relates to compounds for inhibiting a cancer cell or a virus. Particularly, the invention provides compounds for inhibiting, treating and/or preventing cancer and Zika virus.
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ANTI-PARASITIC COMPOUNDS AND USES THEREOF (Fri, 21 Jul 2017)
The present disclosure provides compounds of Formula (I'), Formula (II), and Formula (III). The compounds described herein may useful in treating and/or preventing protozoan infections in a subject in need thereof, treating and/or preventing trypanosomal infections (e.g., Trypanosoma cruzi (T. cruzi) or Trypanosoma brucei infections) and/or plasmodial infections in a subject in need thereof, treating and/or preventing diseases in a subject in need thereof (e.g., Chagas disease, malaria, and/or sleeping sickness), and may be useful in treating and/or preventing infectious diseases in a subject in need thereof. Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including a compound described herein.
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FLAVONOIDE-TYPE COMPOUNDS BEARING AN O-RHAMNOSYL RESIDUE (Fri, 21 Jul 2017)
The present invention relates to compounds of formula (I) These compounds are useful in the treatment of many diseases such as a skin disease, an allergy, an autoimmune disease, a cardiovascular disease, a lung disease, asthma, a bacterial, viral or parasitic disease, metabolic syndrome, cancer, Alzheimer's disease or diabetes and are furthermore useful in the preparation of cosmetics and for use in food and animal feed.
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QUINOLIN-2-ONE DERIVATIVES (Fri, 21 Jul 2017)
Compounds of the formula (I) in which X1, X2, X3, X4, R1, R2, R3, Q and Y have the meanings indicated in Claim 1, are inhibitors of c-Kit kinase, and can be employed for the treatment of cancer.
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ALDOSE REDUCTASE INHIBITORS AND USES THEREOF (Thu, 20 Jul 2017)
The present invention relates to novel compounds and pharmaceutical compositions thereof, and methods for promoting healthy aging of skin, the treatment of skin disorders, the treatment of cardiovascular disorders, the treatment of renal disorders, the treatment of angiogenesis disorders, such as cancer, treatment of tissue damage, such as non-cardiac tissue damage, the treatment of evolving myocardial infarction, and the treatment of various other disorders, such as complications arising from diabetes with the compounds and compositions of the invention. Other disorders can include, but are not limited to, atherosclerosis, coronary artery disease, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, infections of the skin, peripheral vascular disease, stroke, and the like.
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18/19F-LABELLED COMPOUNDS WHICH TARGET THE PROSTATE SPECIFIC MEMBRANE ANTIGEN (Fri, 14 Jul 2017)
This disclosure relates to novel compounds comprising a zwitterionic trifluoroborate prosthetic group which target prostate-specific membrane antigen (PSMA), e.g. in prostate cancer. The compounds have Formula I, wherein each Rl is an anionic group, L is a linker and R2BF3 is - N(R3)2CH2BF3, a pyridinium group substituted with BF3 or methyl BF3, or an azole group substituted with methyl BF3. Methods and uses of imaging and treating PSMA-expressing cancers are also disclosed.
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INHIBITORS OF ATAXIA-TELANGIECTASIA MUTATED AND RAD3-RELATED PROTEIN KINASE (ATR) FOR USE IN METHODS OF TREATING CANCER (Fri, 14 Jul 2017)
The present invention relates to Ataxia-Telangiectasia Mutated and Rad3-related protein kinase (ATR) inhibitors for use in methods of treating BAF-complex deficient cancer. The present invention further provides methods for identifying ATR inhibitors for use in the treatment of BAF complex gene mutant or deficient cancers. Medical uses and methods relating to the treatment of synovial sarcoma using ATR inhibitors are also provided.
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DRUG DELIVERY COMPOSITIONS AND METHODS (Fri, 14 Jul 2017)
One aspect of the present invention is directed to conjugates that comprise a linear polymer carrier, a linker and one or more drugs or imaging agents, as well as pharmaceutical compositions that include such conjugates. The drug may be a platinum-containing drug with a linker comprised of a modified amino acid. The conjugate may alternatively include a metal complexing ligand with a metal used for imaging or chemotherapeutic purposes. Another aspect of the invention is directed to formulations and processes for lyophilization of hyaluronan conjugates. Another aspect of the invention is directed to methods for treating and/or inhibiting cancer utilizing the conjugates and compositions described herein.
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PYRIDINE AND PYRIDIMINE COMPOUNDS AS PI3K-GAMMA INHIBITORS (Fri, 14 Jul 2017)
The present disclosure provides compounds of Formula I, or pharmaceutically acceptable salts thereof, that modulate 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.
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BENZOTHIAZOLE AMPHIPHILES (Fri, 14 Jul 2017)
Disclosed herein, inter alia, are compounds and methods for increasing spine density in a neuron, and for treatment of neuronal diseases and cancer.
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SELECTIVE KILLING OF TUMORS OF THE HEMATOPOIETIC AND LYMPHOID TISSUES (Fri, 14 Jul 2017)
A method for killing hematopoietic and/or lymphoid tissue cancer cells is provided. The method includes a step identifying a subject having hematopoietic and/or lymphoid tissue cancer with circulating cells or DNA containing elevated levels of uracils and AP sites. The hematopoietic and/or lymphoid tissue cancer cells are contacted (i.e., treated) with an alkoxyamino compound having formula I: (I) wherein: (II) R1, R2, R3, R4, R5 are each independently hydrogen (H), C1-6 alkyl, F, C1, or Br; and n is 1 to 5.
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SELECTIVE INHIBITORS OF CLINICALLY IMPORTANT MUTANTS OF THE EGFR TYROSINE KINASE (Fri, 14 Jul 2017)
The present invention provides compounds of Formula (I) or a subgeneric structure or species thereof, or a pharmaceutically acceptable salt, ester, solvate, and/or prodrug thereof, and methods and compositions for treating or ameliorating abnormal cell proliferative disorders, such as cancer, wherein A, R2, R3, R10, E1, E2, E3, Y, and Z are as defined herein.
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FORMULATIONS OF 2-(4-CHLOROPHENYL)-N-((2-(2,6-DIOXOPIPERIDIN-3-YL)-1-OXOISOINDOLIN-5-YL)METHYL)-2,2-DIFLUOROACETAMIDE (Fri, 14 Jul 2017)
Provided herein are lyophilized formulations of 2-(4-chlorophenyl)-N-((2-(2,6- dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide or a stereisomer or mixture of stereisomers, pharmaceutically acceptable salt, tautomer, prodrug, solvate, hydrate, co-crystal, clathrate, or polymorph thereof. Methods of using the formulations and dosage forms for treating, managing, and/or preventing cancer are also provided herein.
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METHODS FOR TREATING CANCER AND THE USE OF BIOMARKERS AS A PREDICTOR OF CLINICAL SENSITIVITY TO THERAPIES (Fri, 14 Jul 2017)
A method of identifying a subject having cancer who is likely to be responsive to a treatment compound, comprising administering the treatment compound to the subject having the cancer; obtaining a sample from the subject; determining the level of a biomarker in the sample from the subject; and diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject changes as compared to a reference level of the biomarker; wherein the treatment compound is a compound of Formula I:
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NOVEL COMPOUNDS WHICH ACTIVATE ESTROGEN RECEPTORS AND COMPOSITIONS AND METHODS OF USING THE SAME (Fri, 14 Jul 2017)
Provided are compounds of formulae provided herein. The compounds may include pathway-preferential estrogens (PaPEs) derivatives with tissue-selective activities. Also provided are pharmaceutical compositions comprising the compounds, as well as methods of treating a disease or condition including administering the compounds. The disease or condition may include postmenopausal symptoms, cardiovascular disease, stroke, vascular disease, bone disease, metabolic disease, arthritis, osteoporosis, obesity, vasomotor/hot flush, cognitive decline, cancer including breast cancer.
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MODULATORS OF 5'-NUCLEOTIDASE, ECTO AND THE USE THEREOF (Fri, 14 Jul 2017)
Compounds that modulate the conversion of AMP to adenosine by 5'- nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5'-nucleotidase, ecto is also provided.
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Uses of labeled HSP90 inhibitors (Fri, 14 Jul 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.
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METHODS OF TREATING CANCER USING 3-(5-AMINO-2-METHYL-4-OXO-4H-QUINAZOLIN-3-YL)-PIPERIDINE-2,6-DIONE (Fri, 14 Jul 2017)
Provided herein are methods of treating, preventing and/or managing cancers, which comprise administering to a patient 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl) piperidine-2,6-dione, or an enantiomer or a mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof.
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HETEROCYCLIC MODULATORS OF LIPID SYNTHESIS (Thu, 13 Jul 2017)
Compounds of formula (X) that are fatty acid synthesis modulators are provided. The compounds may be used to treat disorders characterized by disregulation of the fatty acid synthase function by modulating the function and/or the fatty acid synthase pathway. These compounds are useful in methods for treating such disorders including viral infections, such as hepatits C infection, cancer and metabolic disorders.
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Tricyclopyrazole derivatives (Wed, 12 Jul 2017)
<p id="p-0001" num="0000">Compounds which are tricyclopyrazole derivatives or pharmaceutically acceptable salts thereof, their preparation process and pharmaceutical compositions comprising them are disclosed; these compounds are useful in the treatment of diseases caused by and/or associated with an altered protein kinase activity such as cancer, viral infection, prevention of AIDS development in HIV-infected individuals, cell proliferative disorders, autoimmune and neurodegenerative disorders; also disclosed is a process under Solid Phase Synthesis conditions for preparing the compounds of the invention and chemical libraries comprising a plurality of them.</p>
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DNA TARGETED MONO AND HETERODINUCLEAR COMPLEXES (Fri, 07 Jul 2017)
The invention is related to copper and platin compounds and synthesis method of compounds which are active in cancer cells that show resistance particularly against cisplatin, having a wider effect spectrum in comparison to cisplatin, and a lower toxicity in comparison to cisplatin, having reduced side effects, which can be used as a potential antitumor drug, having anti cancer (cancer treating) and anti oxidant effects, comprising DNA targeted mono and binuclear platin and copper platin complexes and similar functional groups.
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DEUTERATED COMPOUNDS FOR TREATING CANCER AND RELATED DISEASES AND CONDITIONS, AND COMPOSITIONS AND METHODS THEREOF (Fri, 07 Jul 2017)
The invention provides novel chemical compounds useful for treating cancer or a related disease or disorder thereof, and pharmaceutical composition and methods of preparation and use thereof.
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LSD1 INHIBITORS (Fri, 07 Jul 2017)
The present invention relates to compounds that inhibit LSD1 activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of treating cancer using the compounds and pharmaceutical compositions of the present invention.
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USE OF A DHODH INHIBITOR IN COMBINATION WITH AN INHIBITOR OF PYRIMIDINE SALVAGE (Fri, 07 Jul 2017)
Compounds and methods are provided for the treatment of pathogenic virus infections or cancer. The formulations combine an inhibitor of de novo pyrimidine synthesis, and an inhibitor of a pyrimidine salvage pathway enzyme.
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HISTONE DEMETHYLASE INHIBITORS (Fri, 07 Jul 2017)
The present disclosure relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted pyridine derivative compounds, and compositions (including pharmaceutical compositions) that include these compounds. The subject compounds and compositions are useful for inhibition of at least one histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer or neoplastic disease, such as prostate cancer, breast cancer, bladder cancer, lung cancer, melanoma, retinoblastoma, or multiple endocrine neoplasia type 1.
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2H-CHROMENO[2,3-D]PYRIMIDINE-2,4(3H)-DIONES AS NF-KB INHIBITORS (Fri, 07 Jul 2017)
The present invention provides, inter alia, compounds of formula (I) capable of inhibiting NF-KB. Pharmaceutical compositions containing and methods of using the compounds for the treatment of e.g. inflammation, autoimmune diseases or cancer are also provided herein. A, B, C and D are independently selected from the group consisting of carbon and nitrogen. X, Y and Z are independently selected from the group consisting of oxygen, sulfur and NRa.
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SUBSTITUTED BENZOFURANYL AND BENZOXAZOLYL COMPOUNDS AND USES THEREOF (Fri, 07 Jul 2017)
The invention generally relates to substituted benzofuranyl and substituted benzoxazolyl compounds, and more particularly to a compound represented by Structural Formula (I) or (II), or a pharmaceutically acceptable salt thereof, wherein the variables are as defined and described herein. The invention also includes the synthesis and use of a compound of Structural Formula A, or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment of cancer (e.g., mantle cell lymphoma), and other diseases and disorders.
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MULTICYCLIC COMPOUNDS AND USES THEREOF (Fri, 07 Jul 2017)
The present invention relates to multicyclic compounds containing a urea or a guanidine moiety, or pharmaceutically acceptable salts or compositions thereof represented by Structural Formula (IA) or a pharmaceutically acceptable salt thereof and pharmaceutical comopositions comprising the multicyclic compounds. The invention also relates to a method for treating a disease or disorder selected from cancer (e.g., lymphoma, such as mantle cell lymphoma), a neurodegenerative disease, an inflammatory diseases or an immune system disease (e.g., a T-Cell mediated autoimmune disesase) in a subject in need thereof. The method comprises administering to a subject in need thereof a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, or a composition comprising a compound of the invention, or a pharmaceutically acceptable salt thereof.
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BIFUNCTIONAL MOLECULES FOR HER3 DEGRADATION AND METHODS OF USE (Fri, 07 Jul 2017)
The invention provides bifunctional compounds which act as protein degradation inducing moieties for a HER family protein, such as Her3. The invention also provides methods for the targeted degradation of a HER family protein through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to the HER family protein which can be utilized in the treatment of disorders modulated by a HER family protein.
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BIFUNCTIONAL COMPOUNDS FOR HER3 DEGRADATION AND METHODS OF USE (Fri, 07 Jul 2017)
The present invention provides bifunctional compounds which act as protein degradation inducing moieties for a HER family protein, such as Her3. The present invention also provides methods for the targeted degradation of a HER family protein through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to the HER family protein which can be utilized in the treatment of disorders modulated by a HER family protein.
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TRYPTAMINE-BASED SHIP INHIBITORS FOR THE TREATMENT OF CANCER (Fri, 07 Jul 2017)
The present disclosure provides compositions that inhibit the SH2-containing inositol 5'-phosphatase (SHIP), as well as methods using such compositions for use in treating or ameliorating the effects of a medical condition in a subject.
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USE OF BRASSINOSTEROID ANALOGS FOR THE TREATMENT OF DERMAL DISORDERS BY SELECTIVELY MODULATING LIVER X RECEPTORS (LXR) AND DERMAL DISEASE TREATMENT BY BRASSINOSTEROID ANALOGS ACTING AS SELECTIVE LIVER X RECEPTOR (LXR) MODULATORS (Fri, 07 Jul 2017)
The present invention relates to the use of brassinosteroid analogs for the treatment of dermal disorders or conditions. One embodiment is the topical application of at least one brassinosteroid analog described herein for the treatment of psoriasis in a mammal. The present invention describes the use of brassinosteroid analogs of general formula (a). (a) (I) wherein, R1, R2, and R3 are selected from H, H0-, linear or branched C1-C4 alkyl, R5-O-, HCOO-, R5-COO-, -OOC-R6-COO-, p-toluene sulphonate, phosphate, tartrate, maleate, sulphate, fluorine, chlorine, bromine, iodine and methanesulphonate, R4 and R5 are selected from H and linear or branched C1-C4 alkyl, R6 is -(CH2)n- wherein n equals to 1, 2 or 3, and can be a single or double bond An embodiment of the present invention describes a method of therapeutic treatment for psoriasis, skin aging, rosacea, dermatitis, burns, skin cancer and malignancies, and pigmentary derangements, by means of administration of brassinosteroid analogs of general formula (a).
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Substituted bridged urea analogs as sirtuin modulators (Fri, 07 Jul 2017)
Provided herein are novel substituted bridged urea and related analogs and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent. Figure 1. H-NMR Spectrum of Compound 1
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IMAGING OF CREATINE KINASE ENZYME EXPRESSION IN CANCEROUS TISSUES (Fri, 30 Jun 2017)
<p id="p-0001" num="0000">The present technology is directed to apparatuses, machines and methods for determining the level of expression of creatine kinase enzyme in cancerous tissues, as well as for determining malignancy and providing a cancer prognosis. The method is based on overexpression of creatine kinase in cancer tissue and enhanced transformation of injected phosphocreatine substrate into creatine as detectable by NMR.</p>
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NOVEL PYRROLO[3,2-c]PYRIDINE-6-AMINO DERIVATIVES (Fri, 30 Jun 2017)
The present invention relates to novel pyrrolo[3,2-c]pyridine-6-amino derivatives that inhibit the spindle checkpoint function of Monospindle 1 (Mps1 – also known as TTK) kinases. In particular, the present invention relates to isopropyl 6-(2-methoxy-4-(1-5 methyl-1H-1,2,3-triazol-5-yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2- c]pyridine-1-carboxylate and isopropyl 6-(2-methoxy-4-(1-methyl-1H-tetrazol-5- yl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate and their use as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the 10 preparation of these compounds and to pharmaceutical compositions comprising them.
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COMBINATION THERAPY (Fri, 30 Jun 2017)
This invention relates to a combination of gemcitabine-[phenyl-benzoxy-L-alaninyl)]- phosphate (chemical name: 2'-Deoxy-2',2'-difluoro-D-cytidine-5'-O-[phenyl (benzoxy- L- alaninyl)] phosphate) (NUC-1031) and a platinum-based anticancer agent selected from cisplatin, picoplatin, lipoplatin and triplatin. The combinations are useful in the treatment of cancer and particularly biliary tract and bladder cancer.
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CYANOPYRROLIDINE DERVIVATIVES AS INHIBITORS FOR DUBS (Fri, 30 Jun 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 and 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 cancer. Compounds of the invention include compounds having the formula (I): pharmaceutically acceptable salt thereof, wherein R1a, R1b, R1c, R1d, R1e, R1f and A are as defined herein.
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NUCLEIC ACID OLIGOMERS AND USES THEREFOR (Fri, 30 Jun 2017)
Disclosed are nucleic acid oligomer compounds and to their use in compositions and methods for inhibiting proliferation, survival or viability of cancer cells including prostate, lung, pancreatic, breast, cervical and bone cancer cells.
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TDO2 INHIBITORS (Fri, 30 Jun 2017)
Presently provided are inhibitors of cellularly expressed TDO2 and pharmaceutical compositions thereof, useful for modulating an activity of tryptophan 2, 3 dioxygenase; treating immunosuppression; treating a medical conditions that benefit from the inhibition of tryptophan degradation; enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent; and treating tumor-specific immunosuppression associated with cancer.
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STAPLED PEPTIDE INHIBITORS OF NEMO AS POTENTIAL ANTI-INFLAMMATORY AND ANTI-CANCER DRUGS (Fri, 30 Jun 2017)
The invention concerns stapled peptide inhibitors of NEMO which inhibit the Nuclear Factor ĸΒ (NF-ĸΒ) signaling pathway and are useful as medicine candidates, i n particular as anti -inflammatory or anticancer drugs.
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BROMODOMAIN AND EXTRA-TERMINAL PROTEIN INHIBITOR COMBINATION THERAPY (Fri, 30 Jun 2017)
The present disclosure relates generally to compositions and methods of treating cancers, such as glioblastoma and non-Hodgkin's lymphomas, or other cancers in which the subject suffers from an advanced solid tumor, comprising the administration of a bromodomain and extra-terminal protein (BET) inhibitor and at least one chemotherapeutic agent, which does not inhibit BET directly. The BET inhibitor/chemotherapeutic agent combination therapy can yield synergistic effects, thereby increasing the effectiveness of the cancer treatment as compared to the administration of either the BET inhibitor or the chemotherapeutic agent alone.
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HETEROCYCLIC COMPOUNDS AS IMMUNOMODULATORS (Fri, 30 Jun 2017)
Disclosed are compounds of Formula (I'), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.
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INHIBITORS OF THE MENIN-MLL INTERACTION (Fri, 30 Jun 2017)
The present invention is directed to inhibitors of the interaction of menin with MLL and MLL fusion proteins, pharmaceutical compositions containing the same, and their use in the treatment of cancer and other diseases mediated by the menin-MLL interaction.
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COMPOUNDS FOR THE TREATMENT OF CANCER AND INFLAMMATORY DISEASE (Fri, 30 Jun 2017)
Provided herein are compounds that inhibit the phosphorylation of MAPK and thus are compositions and methods for treating cancer and inflammatory disease.
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METHODS OF USE OF A CLASS llA HDAC INHIBITOR (Fri, 30 Jun 2017)
Novel uses of selective class Ila HDAC inhibitors are described.
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INHIBITORS OF GLUCOCORTICOID RECEPTOR (Fri, 30 Jun 2017)
The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer and hypercortisolism.
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IMMUNE CELL-TARGETED PARTICLES (Fri, 30 Jun 2017)
The present disclosure provides particles with a polymeric core containing a pharmaceutically active agent; and an antibody fragment conjugated to the surface of the particle, wherein the antibody fragment targets an endogenous immune cell subset (e.g., an endogenous T-cell or a myeloid-derived suppressor cell). The present invention provides methods for forming and methods for using the particles. The particles described herein may be useful in treating and/or preventing proliferative disease, inflammatory disease, or neoplastic disorders (e.g., cancer, autoimmune diseases). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a particle described herein.
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COMBINATION THERAPY (Fri, 30 Jun 2017)
This invention relates to a combination of gemcitabine-[phenyl-benzoxy-L-alaninyl)]- phosphate (chemical name: 2'-Deoxy-2',2'-difluoro-D-cytidine-5'-O-[phenyl (benzoxy-L- alaninyl)] phosphate)(NUC-1031) and a platinum-based anticancer agent selected from cisplatin, picoplatin, lipoplatin and triplatin. The combinations are useful in the treatment of cancer and particularly biliary tractand bladder cancer.
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ANTI-cMET ANTIBODY (Fri, 30 Jun 2017)
Antibody capable of binding specifically to the human c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor, with an improved antagonistic activity, said antibody comprising a modified hinge region. A composition comprising such an antibody antagonist to c-Met and its use as a medicament for treating cancer.
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Azetidines as MEK inhibitors for the treatment of proliferative diseases (Fri, 30 Jun 2017)
Disclosed are compounds of Formula (I) and pharmaceutically acceptable salts and solvates thereof. Such compounds are MEK inhibitors and are useful in the treatment of proliferative diseases, such as cancer. Also disclosed are pharmaceutical compositions containing such compounds as well as methods of using the compounds and compositions of the invention in the treatment of cancer.
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Use of the antibody I-3859 for the detection and diagnosis of cancer (Fri, 30 Jun 2017)
The present invention relates to the use of a novel, isolated anti-CXCR4 antibody in the diagnosis of cancer. In particular, methods for diagnosing and/or prognosing an oncogenic disorder associated with CXCR4 expression, are disclosed.
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SUBSTITUTED 6,5-FUSED BICYCLIC HETEROARYL COMPOUNDS (Fri, 30 Jun 2017)
[01288] The present invention relates to substituted 6,5 -fused bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof.
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BROMODOMAIN-INHIBITING COMPOUNDS AND PHARMACEUTICAL COMPOSITION COMPRISING SAME FOR PREVENTING OR TREATING A CANCER (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">Provided is a novel compound having bromodomain and extra terminal domain (BET) protein inhibiting activities, and a pharmaceutical composition comprising the same which can be useful for prevention or treatment of precancerous transformation or cancer.</p>
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QUINOLINE DERIVATIVES AS SMO INHIBITORS (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">Disclosed are quinoline derivatives as hedgehog pathway inhibitors, especially as SMO inhibitors. Compounds of the present invention can be used in treating diseases relating to hedgehog pathway including cancer.</p>
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QUINOXALINE COMPOUNDS AND USES THEREOF (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">This invention provides compounds of formula I and subsets thereof: wherein T, J, R, R<sup>4</sup>, R<sup>q</sup>, o, R<sup>A</sup>, and R<sup>B </sup>and subsets thereof are as described in the specification. The compounds are inhibitors of NAMPT and are thus useful for treating cancer, inflammatory conditions, or T-cell mediated autoimmune disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.96mm" wi="65.53mm" file="US20170174704A1-20170622-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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MODIFICATION OF CUPREDOXIN DERIVED PEPTIDES AND METHODS OF USE THEREOF (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The present invention provides modified cupredoxin derived peptides with pharmacologic activity that have improved pharmacokinetic properties, and methods to use them to treat mammals suffering from various conditions related to the pharmacologic activities. Modifications of the cupredoxin derived peptides include amino acid sequence variants and structural derivations that increase the plasma half-life of the peptide, increase the specific activity of the pharmacologic activity, decrease immunogenicity, and decrease the biotransformation of the peptides. The modified cupredoxin derived peptides can be used in methods to treat mammals for cancer, conditions related to inappropriate angiogenesis, viral and bacterial infections, and specifically HIV and malaria, conditions related to ephrin signaling, and to deliver cargo compounds, including diagnostic compounds, to cancer cell</p>
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Protein-Based Molecular Temperature Switch (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">A region of the TRPM8 protein that functions as a temperature switch (FIG. <b>1</b>) has been identified, and can be expressed, purified and applied in combination with other proteins. The function of the switch is maintained even when the region or domain is isolated from the entire protein. As the protein domain is a temperature switch, it can be used to control other proteins and signaling pathways in vitro and in vivo; and 2) TRPM8 is a therapeutic target that is being pursued primarily for intervention in pain (neuropathic and inflammatory) and cancer.</p>
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VITAMIN D RECEPTOR-COREGULATOR INHIBITORS (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">Described herein are compounds, pharmaceutical compositions and methods for inhibiting the expression of a vitamin D receptor target gene, inhibiting interactions between the vitamin D receptor and at least one vitamin D receptor coactivator, for treating cancer in a subject, and for inhibiting angiogenesis in a subject.</p>
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HETEROCYCLIC COMPOUNDS AS IMMUNOMODULATORS (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">Disclosed are compounds of Formula (I′), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.06mm" wi="61.30mm" file="US20170174679A1-20170622-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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HETEROCYCLIC COMPOUND (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">Provided is a compound or a salt thereof, which has an excellent JAK inhibitory action, and is useful as a prophylactic or therapeutic agent for autoimmune diseases (rheumatoid arthritis, psoriasis, inflammatory bowel disease, Sjogren's syndrome, Behcet's syndrome, multiple sclerosis, systemic lupus erythematosus, etc.), cancer (leukemia, uterine leiomyosarcoma, prostate cancer, multiple myeloma, cachexia, myelofibrosis, etc.) and the like. The present invention relates to a compound represented by the formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="40.81mm" wi="53.42mm" file="US20170174682A1-20170622-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as defined in the present specification, or a salt thereof.</p>
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SUBSTITUTED INDOLE MCL-1 INHIBITORS (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The present invention provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present invention 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.</p>
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METHODS (AMACR) (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">A method of measuring α-methylacyl-CoA racemase (AMACR) activity in a sample is described comprising the steps of: (i) providing a sample; (ii) contacting said sample with a substrate compound that undergoes elimination of hydrogen and a leaving group catalysed by said AMACR to produce a product compound having an additional carbon-carbon double bond; and (iii) measuring the amount of said leaving group and/or of said product compound and/or of unreacted substrate compound. Also provided are methods of diagnosis and medical imaging, in particular for use in diagnosing prostate cancer. Also provided are substrate compounds of Formula 1 for use in the methods described herein.</p>
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NANOPARTICLE FORMULATIONS AND USES THEREOF (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The present invention provides compositions comprising nanoparticles comprising: 1) a drug, such as a hydrophobic drug derivative; and 2) a carrier protein. Also provided are methods of treating diseases (such as cancer) using the compositions, as well as kits and unit dosages.</p>
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ANTIMITOTIC AMIDES FOR THE TREATMENT OF CANCER AND PROLIFERATIVE DISORDERS (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">Novel, antimitotic heteroaryl amides and pharmaceutically acceptable salts of Formula I where Ar, R<sup>5</sup>, R<sup>6</sup>, R<sup>8</sup>, R<sup>9</sup>, R<sup>11</sup>, X<sup>1</sup>, and X<sup>2 </sup>are as defined herein, as compounds for treatment and prevention of cancer and proliferative diseases and disorders.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.65mm" wi="62.99mm" file="US20170172984A1-20170622-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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TREATMENT OF CANCERS HAVING RESISTANCE TO CHEMOTHERAPEUTIC AGENTS (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The present invention provides compositions and methods for treating cancer with DAST, 4{4-[3-(4-chloro-3-trifluoromethylphenyl)-ureido]-3-fluorophenoxy}-pyridine-2-carboxylic acid methylamide of the formula I, including all polymorphs, hydrates, pharmaceutically acceptable salts, metabolites, prodrugs, solvates or combinations thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="26.67mm" wi="75.35mm" file="US20170172989A1-20170622-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">Any cancer can be treated, including cancers that have acquired resistance to another therapeutic agent, such as kinase inhibitors. DAST can also be used to treat cancers which have become refractory to other chemotherapeutic agents</p>
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IMAGE GUIDED THERAPY FOR CANCER (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The invention provides a method to treat cancer in an animal comprising administering a tetra-arylethylene cation to the animal.</p>
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COMPOUNDS FOR THE TREATMENT OF CANCER AND INFLAMMATORY DISEASE (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">Provided herein are compounds that inhibit the phosphorylation of MAPK and thus are useful in compositions and methods for treating cancer and inflammatory disease.</p>
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BENZIMIDAZOLE DERIVATIVES AS ERBB TYROSINE KINASE INHIBITORS FOR THE TREATMENT OF CANCER (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">Provided herein are benzimidazole derivatives, for example, of Formula (I), and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of a proliferative disease.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.79mm" wi="56.98mm" file="US20170174697A1-20170622-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMBINATION THERAPY FOR CANCER (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The present invention provides preparation of medicaments for use in treating and methods of treating non-small cell lung cancer in a patient comprising: [5-(4-ethyl-piperazin-1-ylmethyl)-pyridin-2-yl]-[5-fluoro-4-(7-fluoro-3-isopropyl-2-methyl-3H-benzoimidazol-5-yl)-pyrimidin-2-yl]-amine, or a pharmaceutically acceptable salt thereof, in combination, as further described herein, with an anti-VEGFR2 antibody, preferably, ramucirumab.</p>
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PHARMACEUTICAL FORMULATIONS OF A PAN-RAF KINASE INHIBITOR, PROCESSES FOR THEIR PREPARATION, AND METHODS OF USE (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The invention relates to a pharmaceutical composition comprising Compound 1 or a pharmaceutically acceptable salt thereof for the treatment of cancer and a process for its preparation. The invention also relates to administering the pharmaceutical composition to a patient according to an intermittent dosing regimen.</p>
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METHOD FOR USE OF HOMOPIPERAZINIUM COMPOUNDS IN THE TREATMENT OF CANCER (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">A method for treating cancer comprising administering to a patient in need thereof an effective amount of a compound having the formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.95mm" wi="26.67mm" file="US20170173040A1-20170622-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sub>1 </sub>and R<sub>2 </sub>are independently alkyl of 1 to 6 carbon atoms or cycloalkyl of 3 to 6 carbon atoms, Xa is CH or N, Ya is hydrogen or a substituent, each of which is independently selected; n is an integer from 1 to 5, J is a counter ion.</p>
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WITHACNISTIN COMPOUNDS FOR TREATMENT OF CANCER (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The subject invention pertains to the treatment of tumors and cancerous tissues and the prevention of tumorigenesis and malignant transformation through the modulation of STAT3 intracellular signaling. The subject invention concerns pharmaceutical compositions containing one or more withacnistin compounds, or a pharmaceutically acceptable salt or derivative thereof. In one embodiment, the subject invention concerns a composition comprising a mixture of withacnistin, 3-methoxy-2,3-dihydrowithacnistin, and 3-ethoxy-2,3-dihydrowithacnistin, or a salt or derivative of any of the foregoing. Another aspect of the invention concerns methods of inhibiting the growth of a tumor by administering one or more withacnistin compounds, or a pharmaceutically acceptable salt or derivative thereof, to a patient, wherein the tumor is characterized by the constitutive activation of the STAT3 intracellular signaling pathway. The present invention further pertains to methods of moderating the STAT3 signaling pathway in vitro or in vivo using one or more withacnistin compounds, or a pharmaceutically acceptable salt or derivative thereof.</p>
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EXOGENOUS TAP INHIBITOR ARMED ONCOLYTIC VIRUSES AND THERAPEUTIC USES THEREOF (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The present invention relates to exogenous TAP inhibitor armed oncolytic viruses that replicate selectively in cancer cells, evade CD8+ cytolytic T-cells, and induce the immune system to recognize tumor cells. Preferred viruses of the invention have a heterologous gene that encodes a function that affects antigen presentation by inhibiting TAP. The viruses of the invention also comprise one or more heterologous genes encoding immunomodulatory polypeptides, prodrug converting enzymes, or matrix degrading enzymes. Compositions and therapeutic methods using the oncolytic viruses are also provided, including compositions and therapeutic methods for treating cancers, such as melanoma, head and neck cancer, ovarian cancer, breast cancer, glioblastoma, bladder cancer, prostate cancer, lung cancer, liver cancer, colorectal cancer, pancreatic cancer, and renal cancer.</p>
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Antibody to Mucin 4 (MUC4) Glycopeptide and Uses Thereof (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The present invention provides: an antibody that has specificity for MUC 4 having a sugar chain structure that is expressed at a high level in cancer cells; a glycopeptide that constitutes an antigen that is suitable for producing this antibody; and a new means and method for the diagnosis, prevention, and/or treatment of cancer by means of the aforementioned antibody. The present invention relates to a monoclonal antibody against a glycopeptide. The glycopeptide comprises a human MUC 4 tandem unit peptide having an amino acid sequence represented by SEQ ID NO: 1, and an O-linked sugar chain. The O-linked sugar chain is N-acetylgalactosamine (GalNAc) and binds to threonine, which is the 8th amino acid of the tandem unit peptide. The present invention further includes: a glycopeptide for use in the production of a monoclonal antibody against human MUC 4; a method for detecting MUC 4 in a human body fluid sample; a kit that includes the abovementioned monoclonal antibody; and a pharmaceutical composition for the prevention and/or treatment of malignant tumors that contains the abovementioned monoclonal antibody as an active component.</p>
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COMPOUND ISOLATED FROM ISODON FORRESTII VAR. FORRESTII AND PREPARATION METHOD AND APPLICATIONS THEREOF (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">A compound of Formula I or pharmaceutically acceptable salt thereof and its preparation method and applications, the new structure of the compound of formula I has not been reported in literature. It is isolated from <i>Isodon forrestii </i>var. <i>forrestii </i>and can be a compound served as Trx1 selective inhibitor. The present invention further discloses a pharmaceutical composition, preparation of the compound of</p> <p id="p-0002" num="0000">Formula I and its applications in preparing medicines for preventing or treating cancer. Iso A of the present invention has the advantages of low toxicity, high safety and strong pharmacological effect, which suggests a potential prospect in pharmaceutical applications.</p>
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HDAC INHIBITOR COMPOUNDS AND METHODS OF TREATMENT (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The instant invention describes hydrazide-containing compounds having therapeutic activity, and methods of treating disorders such as cancer, tumors and cell proliferation related disorders, or affect cell differentiation, dedifferentiation or transdifferentiation.</p>
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NAT10 MODULATORS FOR TREATING OR PREVENTING LAMINOPATHIES, AGING AND CANCER (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The invention relates to compounds in the treatment or prevention of disorders associated with Lamin A and/or Lamin C depletion or LMNA mutations, such as laminopathy, premature ageing disorders, normal ageing and cancer (such as a cancer characterised by low levels of LMNA expression).</p>
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3-SUBSTITUTED CARBONYL-NAPHTHO[2,3-B]FURANE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The present invention provides a compound of the following Formula (1) 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="25.06mm" wi="41.91mm" file="US20170174646A1-20170622-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein X is an oxygen atom and the like; Y is —CO—, —SO<sub>2</sub>— and the like; R<sup>1 </sup>is an optionally-substituted C<sub>1-6 </sub>alkyl group, an optionally-substituted C<sub>1-6 </sub>alkylcarbonyl group and the like; R<sup>2 </sup>is an optionally-substituted C<sub>1-6 </sub>alkyl group, an optionally-substituted C<sub>1-6 </sub>alkoxy group, an optionally-substituted amino group, an optionally-substituted 5- to 12-membered monocyclic or polycyclic saturated heterocyclic group and the like; R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, and R<sup>6 </sup>are independently a hydrogen atom and the like which exhibits excellent effects in suppressing the proliferation and sphere-forming ability of cancer cells, and can be useful as an antitumor drug or cell growth inhibitor.</p>
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HISTONE DEMETHYLASE INHIBITORS (Fri, 23 Jun 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 3-aminopyridine derivative compounds, substituted 3-aminopyridazine 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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HEAT SHOCK PROTEIN 70 (HSP-70) RECEPTOR LIGANDS (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">Inducible HSP70 is overexpressed in a wide spectrum of human tumors and its expression correlates with metastasis and poor outcomes to radiation and chemotherapy in patients. Identification of small molecule inhibitors of HSP70 pose a new therapy to cancer treatment. HS72, a benzimidazole piperidinyl carboxamide has been identified as an allosteric inhibitor for HSP70 and has demonstrated good tumor growth inhibition in vivo.</p>
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PYRROLOPYRIMIDINE COMPOUNDS, USE AS INHIBITORS OF THE KINASE LRRK2, AND METHODS FOR PREPARATION THEREOF (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The present disclosure is concerned with certain pyrrolopyrimidine compounds that are capable of inhibiting certain protein kinases, and especially the leucine-rich repeat kinase 2 (LRRK2) protein. Compounds of the present disclosure can be used to treat a number of disorders caused by or associated with abnormal LRRK2 kinase activity. Compounds of the present disclosure can be used to treat disorders including neurodegenerative diseases such as Parkinson's disease; precancerous conditions and cancer; autoimmune disorders such as Crohn's disease, rheumatoid arthritis and psoriasis; and leprosy (Hansen's disease). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.</p>
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COMPOUNDS USEFUL AS KINASE INHIBITORS (Fri, 23 Jun 2017)
This invention relates to novel compounds. The compounds of the invention are tyrosine kinase inhibitors. Specifically, the compounds of the invention are useful as inhibitors of Bruton's tyrosine kinase (BTK).The invention also contemplates the use of the compounds for treating conditions treatable by the inhibition of Bruton's tyrosine kinase, for example cancer, lymphoma, leukemia and immunological diseases.
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Novel Compounds (Fri, 23 Jun 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 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 cancer. Compounds of the invention include compounds having the formula (I): (I) or a pharmaceutically acceptable salt thereof, wherein R1a, R1b, R1c, R1d, R1e, R1f, R1g, R2, X, L and A are as defined herein.
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DIPHENYLPROPANE COMPOUNDS AND THEIR CYTOTOXIC ACTIVITY (Fri, 23 Jun 2017)
The invention relates to new derivatives of 1,3-diphenylpropane described by general formula (I), demonstrating cytotoxic activity against cancer cells, to be used as drugs in anticancer therapy, and characterized by reduced undesired side effects in comparison to related derivatives of chalcones.
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1H-IMIDAZO[4,5-B]PYRIDINYL AND 2-OXO-2,3-DIHYDRO-1H-IMIDAZO[4,5-B]PYRIDINYL HETEROCYCLIC BET BROMODOMAIN INHIBITORS (Fri, 23 Jun 2017)
Substituted 1H-imidazo[4,5-b]pyridinyl and 2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridinyl heterocyclic compounds, which are useful as inhibitors of BET protein function by binding to bromodomains, compositions comprising said compounds, and their use in therapy are disclosed herein. These compounds are useful in the treatment of diseases and conditions, such as, cancer, autoimmune diseases, inflammation and cardiovascular diseases.
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QUINOLIZINONE DERIVATIVES AS PI3K INHIBITORS (Fri, 23 Jun 2017)
Disclosed are compounds of formula (I), their tautomeric forms, stereoisomers, and pharmaceutically acceptable salts thereof (I), wherein R1-R5, and n are as defined in the specification, pharmaceutical compositions including a compound, tautomer, stereoisomer, or salt thereof, and methods of treating or preventing diseases or disorders, for example, cancer, that are amenable to treatment or prevention by inhibiting the PI3K enzyme of a subject.
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SMALL MOLECULES AGAINST CANCER (Fri, 23 Jun 2017)
Compounds capable of, or usable in, killing cancer cells, and/or modulating a biological activity of a chemokine, and/or inhibiting a kinase, and/or treating diseases and disorders associated with a biological activity of a chemokine and/or cell migration, and/or treating disease and disorders such as cancer and inflammatory diseases and disorders, are provided herein. The compounds are listed in Tables 2, 4 and 5, and/or are represented by Formulae I, IV, V and VI, as defined in the specification. Methods utilizing these compounds are also provided.
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SMALL MOLECULES FOR INHIBITING CHEMOKINE ACTIVITY, A KINASE ACTIVITY AND/OR CANCER CELLS GROWTH (Fri, 23 Jun 2017)
Compounds capable of, or usable in, inducing death of cancer cells and/or modulating a biological activity of a chemokine e.g., cell migration, and/or treating diseases and disorders associated with a biological activity of a chemokine and/or cell migration, and/or inhibiting a kinase and/or in treating a disease or disorder associated with an activity of a kinase, such as cancer and inflammatory diseases and disorders, are provided herein. The compounds are collectively represented by Formulae (Ia) or (Ib): wherein A, B D, E, G and R1-R5 are as defined in the specification.
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INHIBITION OF CYTOKINE-INDUCED SH2 PROTEIN IN NK CELLS (Fri, 23 Jun 2017)
The present invention relates to therapeutic and prophylactic methods based on inhibition of CIS in NK cells. In particular, the present invention relates to treating or preventing a NK-responsive condition by administering to a subject a CIS inhibitor, or administering CIS-inhibited NK cells. The invention further relates to methods for identifying a CIS inhibitor, and for determining a likelihood of cancer response to treatment with CIS inhibition.
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METAL COMPLEXED THERAPEUTIC AGENTS AND LIPID-BASED NANOPARTICULATE FORMULATIONS THEREOF (Fri, 23 Jun 2017)
Provided herein is a pharmaceutical formulation for delivery of a therapeutic agent having a metal complexation moiety and a solubility in water or a metal ion solution of less than 1 mg/ml. Said formulation comprises the therapeutic agent and a metal ion complexed inside a lipid-based nanoparticle formulation.
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HETEROCYCLES USEFUL AS ANTI-CANCER AGENTS (Fri, 23 Jun 2017)
Compounds of Formula (I) are shown below, and their pharmaceutically acceptable salts, hydrates, or solvates thereof. It involves pharmaceutical compositions of these compounds, their preparation, and their utilities in treating diseases and disorders, including cancers.
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COMPOUNDS, COMPOSITIONS AND METHODS OF TREATING CANCER (Fri, 23 Jun 2017)
Disclosed are compounds of formulas I and II, in which R, R0, R1-R4, R7-R10, n, X, Y, Y', and E are as described herein, pharmaceutical compositions containing such compounds. The compounds and pharmaceutical compositions are for use in treating or preventing diseases, for example, cancer.
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NAPTHOQUINONES, PRO-DRUGS, AND METHODS OF USE THEREOF (Fri, 23 Jun 2017)
Provided herein are naphthoquinones compounds such as those with a hydrogen bond donating group of the formula (I): wherein: R1, R2, R3, R4, R5, and n are as defined herein. Also provided herein are pharmaceutical composition of the present compounds and methods of treatment using the compounds including their use in the treatment of cancer.
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PROCESS FOR THE PREPARATION OF TRICYCLIC PI3K INHIBITOR COMPOUNDS AND METHODS FOR USING THE SAME FOR THE TREATMENT OF CANCER (Fri, 23 Jun 2017)
The present disclosure provides for methods for preparing tricyclic PI3K inhibitor compounds in high yield and purity in aqueous solvent systems.
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NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO (Fri, 23 Jun 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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PYRROLOPYRIMIDINE COMPOUNDS, USE AS INHIBITORS OF THE KINASE LRRK2, AND METHODS FOR PREPARATION THEREOF (Fri, 23 Jun 2017)
The present disclosure is concerned with certain pyrrolopyrimidine compounds that are capable of inhibiting certain protein kinases, and especially the leucine-rich repeat kinase 2 (LRRK2) protein. Compounds of the present disclosure can be used to treat a number of disorders caused by or associated with abnormal LRRK2 kinase activity. Compounds of the present disclosure can be used to treat disorders including neurodegenerative diseases such as Parkinson's disease; precancerous conditions and cancer; autoimmune disorders such as Crohn's disease, rheumatoid arthritis and psoriasis; and leprosy (Hansen's disease). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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TRITERPENE SAPONIN VARIANTS, METHODS OF SYNTHESIS AND USE THEREOF (Fri, 23 Jun 2017)
A number of triterpene saponin variants with different modifications on their central glycosyl ester linkage are described. Also described are methods of making and method of using such triterpene saponin variants.
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COMPOSITIONS FOR THERAPEUTICS, TARGETED PET IMAGING AND METHODS OF THEIR USE (Fri, 23 Jun 2017)
Described herein is a chelator for radiolabels (e.g., 89Zr) for targeted PET imaging that is an alternative to DFO. In certain embodiments, the chelator for 89Zr is the ligand, 3,4,3-(LI-1,2- HOPO) ("HOPO"), which exhibits equal or superior stability compared to DFO in chemical and biological assays across a period of several days in vivo. As shown in FIG. 1, the HOPO is an octadentate chelator that stabilizes chelation of radiolabels (e.g., 89Zr). A bifunctional ligand comprising p-SCN-Bn-HOPO is shown in FIG. 4 and FIG. 5. Such a bifunctional ligand can eliminate (e.g., 89Zr) loss from the chelate in vivo and reduce uptake in bone and non-target tissue. Therefore, the bifunctional HOPO ligand can facilitate safer and improved PET imaging with radiolabeled antibodies.
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NANOSCALE PLATINUM COMPOUNDS AND METHODS OF USE THEREOF (Fri, 23 Jun 2017)
The invention is directed to biocompatible conjugated polymer nanoparticles including a copolymer backbone, a plurality of sidechains covalently linked to said backbone, and a plurality of platinum compounds dissociably linked to said backbone. The invention is also directed to dicarbonyl-lipid compounds wherein a platinum compound is dissociably linked to the dicarbonyl compound. The invention is also directed to methods of treating cancer or metastasis. The methods includes selecting a subject in need of treatment for cancer or metastasis and administering to the subject an effective amount of any of the nanoparticles, compounds, or compositions of the invention.
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QUINAZOLINE DERIVATIVE (Thu, 22 Jun 2017)
Provided are a quinazoline derivative, a pharmaceutical composition containing the same, a method for preparation of said derivative, and an application of same as an anti-cancer drug.
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AMINOPYRIMIDINE COMPOUNDS AS INHIBITORS OF T790M CONTAINING EGFR MUTANTS (Thu, 22 Jun 2017)
This invention relates to novel compounds of formula (I) which are inhibitors of T790M containing EGFR mutants, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy for the prevention or treatment of cancer.
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PYRIDINE AMIDOPYRIMIDINE DERIVATIVE, PREPARATION METHOD AND USE THEREOF (Thu, 22 Jun 2017)
The present invention relates to pyridinylaminopyrimidine derivatives represented by the following formula (I), and pharmaceutically acceptable salts, preparation process and use thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , m and A are defined as in the description. Pyridinylaminopyrimidine derivatives of the present invention can selectively inhibit the activity of mutant-type epidermal growth factor receptor (EGFR), have a good inhibition for the cancer cell proliferation, and therefore can be used as a therapeutic agent for treating tumors and relevant diseases.
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CHEMICAL INHIBITOR OF P53-SNAIL BINDING AND PHARMACEUTICAL COMPOSITION FOR TREATING CANCER DISEASE CONTAINING SAME AS ITS ACTIVE INGREDIENT (Thu, 22 Jun 2017)
Provided are compounds for inhibiting Snail-p53 binding and therapeutic agents for cancer including the compounds as an effective component. The Snail-p53 binding inhibitors induce expression of p53 in K-Ras mutant cell lines, thereby enabling effective treatment or prevention of K-Ras mutant cancer, such as, pancreatic cancer, lung cancer, cholangioma, and colon cancer, of which diagnosis or treatment is not easy.
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CHEMICAL COMPOUND FOR INHIBITION OF SHP2 FUNCTION AND FOR USE AS AN ANTI-CANCER AGENT (Fri, 16 Jun 2017)
This invention provides a compound that is 4,4'-(4'-Carboxy)-4-nonyloxy-[1,1'-biphenyl]-3,5-diyl)dibutanoic acid (CNBDA), derivative compounds of CNBDA, and pharmaceutical compositions thereof. The derivative compounds of CNBDA have one or more of the following substitutions (a) replacement of one or both of the carboxylic acid groups of the CNBDA compound with an organic acid group having 1-3, or 5-30, or more carbon atoms in chain length, wherein the carbon atom chains are either saturated, partially saturated, or unsaturated with respect to the carbon to carbon bonding, (b) replacement of the carboxylic groups of (a) with a phosphate, a sulphate, an amide, a hydroxyl, an aldehyde, or a halide group, and (c) replacement of the nonane group with an alkane having a carbon chain length of 1-8 or 10-30, or more carbon atoms. A method of treating a patient having cancer is provided.
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VESICLE CONTAINING METALLIC NANOPARTICLE AND METHOD FOR PRODUCTION THEREOF (Fri, 16 Jun 2017)
Disclosed is a method of producing a vesicle containing a metallic nanoparticle that is covalently bound to at least one hydrophilic polymer and at least one hydrophobic polymer, wherein the method involves dispersing the polymer-bound metallic nanoparticle in an organic solvent, adding an aqueous solution containing a dispersing aid to form a mixed solution, sonicating the mixed solution to form an emulsion; and removing the organic solvent from the emulsion until the vesicle forms. Using this method, the formed vesicle has a diameter of 20-150 nm, which is useful for a method of conducting photothermal therapy (PTT) for killing cells, such as cancer cells.
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LIPOPHILIC ANALOGS OF CJ-16264, METHODS OF USE, AND SYNTHESIS THEREOF (Fri, 16 Jun 2017)
In one aspect, the present disclosure provides compounds and derivatives of CJ-16,264 of the formula (I) wherein the variables are as defined herein. The application also provides compositions, methods of treatment, and methods of synthesis thereof. In some embodiments, these compounds are used in the treatment of bacterial infections or in the treatment of cancer.
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SUBSTITUTED BENZIMIDAZOLIUM, PYRIDO-IMIDAZOLIUM, OR PYRAZINO-IMIDAZOLIUM COMPOUNDS AS CHEMOTHERAPEUTICS (Fri, 16 Jun 2017)
Provided herein are compounds of the formula:(I) wherein: R1, R2, R3, R4, R5, X, A1, A2, A3, and A4 are as defined herein. In some aspects, these compounds may be used to treat cancer and other hyperproliferative disease. In some aspects, compositions, methods of treatment, and methods of synthesis are also provided herein.
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POLYMERIC DRUG DELIVERY SYSTEMS FOR TREATMENT OF DISEASE (Fri, 16 Jun 2017)
Provided are compositions and nanoparticle formulations that may be used, e.g., to deliver a therapeutic compound to a subject. In some embodiments, the nanoparticles may be used to deliver one or more chemotherapeutic agents to treat a cancer such, e.g., as a pancreatic ductal adenocarcinoma.
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FUMAGILLOL DERIVATIVES AND POLYMORPHS THEREOF (Fri, 16 Jun 2017)
The present disclosure relates to salts and polymorphs of aminoalkylfumagillol carbamates (e.g., fumagill-6-yl N-(trans-4-aminocyclohexyl)carbamate benzenesulfonic acid salt and fumagill-6-yl N-(trans-4-aminocyclohexyl)carbamate hydroxynaphthoic acid salt). The polymorphs are characterized by X-ray powder diffraction, differential scanning calorimetry, and thermogravimetric analysis, among other methods. The polymorphs and salts can be used as intermediates in the production of fumagillol derivatives (e.g., polymer-conjugated fumagillol derivatives) as well as therapeutic agents for the treatment of various diseases and conditions such as cancer.
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MODULATION OF GLOBOSERIES GLYCOSPHINGOLIPID SYNTHESIS AND CANCER BIOMARKERS (Fri, 16 Jun 2017)
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 disgnostic and therapeutic uses.
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THERAPEUTIC COMPOUNDS (Fri, 16 Jun 2017)
The invention provides compounds of formula (I): and salts thereof, wherein R1, R2, R3, B, X, Y, and Z have any of the values defined herein. The invention also provides pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, processes for preparing compounds of formula (I) and salts thereof, intermediates useful for preparing compounds of formula (I) and salts thereof, and therapeutic methods for treating cancer using a compound of formula (I) or a pharmaceutically acceptable salt thereof.
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INHIBITORS FOR PROLIFERATING CELL NUCLEAR ANTIGEN AND USES (Fri, 16 Jun 2017)
The present invention relates to series of compounds as an inhibitor targeting Proliferating Cell Nuclear Antigen (PCNA). Pharmaceutical compositions of those compounds and methods of using them in the treatment of cancer are within the scope of this disclosure.
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BENZOTHIADIAZINE COMPOUNDS (Fri, 16 Jun 2017)
The invention is directed to substituted benzothiadiazine derivatives. Specifically, the invention is directed to compounds according to Formula (I):wherein R, R1, R2, R3, R4 and R5 are as defined herein. 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, 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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HYDROXAMIC ACID-BASED COMPOUNDS (Fri, 16 Jun 2017)
The present invention relates to hydroxamic acid-based compounds, their intermediates, preparation and uses. The compounds are useful in imaging, particularly for the imaging of tumours and cancer, and especially for the imaging of prostate cancer. The present invention also relates to compositions including the compounds, and to methods of imaging cells, in vitro biopsy samples and/or patients using the compounds.
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GOLD PORPHYRIN-PEG CONJUGATES AND METHODS OF USE (Fri, 16 Jun 2017)
Disclosed are conjugates, compositions, and methods that include or use one or more gold (III) porphyrin complexes. Preferred conjugates are gold (III) porphyrin-poly (ethylene glycol) (PEG) conjugates. Preferred compositions and methods include or use such gold (III) porphyrin-PEG conjugates. Disclosed is a method for treatment of cancer comprising administering to a human in need of such treatment a composition containing a therapeutically effective amount of gold (III) porphyrin-poly (ethylene glycol) (PEG) conjugates. The gold (III) porphyrin-PEG conjugates can be in the form of nanostructures formed by self-assembly of the gold (III) porphyrin-PEG conjugates; or nanocomposites formed by encapsulation of other therapeutic agents by the nanostructures of gold (III) porphyrin-PEG conjugates.
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CPAP-TUBULIN MODULE (Fri, 16 Jun 2017)
The invention relates to CPAP-tubulin inhibitors having the general formula (1) or a physiologically acceptable salt thereof; and their use as cancer therapeutics.
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MONOMALEIMIDE-FUNCTIONALIZED PLATINUM COMPOUNDS FOR CANCER THERAPY (Fri, 16 Jun 2017)
The present invention relates to novel monomaleimide-functionalized platinum compounds of formula (I), including in particular novel monomaleimide-functionalized oxaliplatin and carboplatin derivatives, as well as their use as medicaments, particularly for the treatment or prevention of cancer.
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COMBINED PREPARATIONS OF PKM2 MODULATORS AND HMGB1 (Fri, 16 Jun 2017)
The present invention relates to a combined preparation comprising (i) a modulator of pyruvate kinase M2 (PKM2) activity, and (ii) an agent providing high mobility group box 1 (HMGB1) polypeptide or a derivative thereof. The present invention also relates to the aforesaid combined preparation for use as a medicament and for use in the treatment of inappropriate cellular proliferation, preferably in the treatment of cancer. Moreover, the present invention relates to a method for determining whether a subject suffering from inappropriate cellular proliferation is amenable to a treatment comprising administration of a modulator of PKM2 activity as the only PKM2 inhibitor and to treatment methods related thereto.
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COMPOSITION OF ANTIBODY CONSTRUCT-AGONIST CONJUGATES AND METHODS OF USE THEREOF (Fri, 16 Jun 2017)
Various antibody construct compositions are disclosed. The compositions of antibody construct-immune stimulatory compound conjugates are also provided. Additionally provided are the methods of preparation and used of the antibody construct-immune stimulatory compound conjugates. This includes methods for treating disorders, such as cancer. A genus of STING agonist compounds and method of synthesis is also disclosed.
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Thienopyrimidine inhibitors of atypical protein kinase C (Fri, 16 Jun 2017)
The present invention provides a compound of formula (1) or a salt thereof, wherein R', R2 , R3,R4 ,R5 , R6 , A, G, M, Q and X are as defined herein. A compound of formula (1) and its salts have a PKC inhibitory activity, and may be used to treat proliferative disorders.
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Androgen receptor modulator for the treatment of prostate cancer and androgen receptor-associated diseases (Fri, 16 Jun 2017)
A hydantoin compound useful for the prevention or treatment of hyperproliferative diseases or disorders
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TREATMENT OF HOT FLUSHES, VASOMOTOR SYMPTOMS, AND NIGHT SWEATS WITH SEX STEROID PRECURSORS IN COMBINATION WITH SELECTIVE ESTROGEN RECEPTOR MODULATORS (Thu, 15 Jun 2017)
Novel methods for reduction or elimination of the incidence of hot flushes, vasomotor symptoms, and night sweats while decreasing the risk of acquiring breast, uterine or endometrial cancer and furthermore having beneficial effect by inhibiting the development of osteoporosis, hypercholesterolemia, hyperlipidemia, atherosclerosis, hypertension, insulin resistance, diabetes type 2, loss of muscle mass, adiposity, Alzheimer's disease, loss of cognition, loss of memory, or vaginal dryness in susceptible warm-blooded animals including humans involving administration of an amount of a sex steroid precursor, particularly dehydroepiandrosterone (DHEA) and an antiestrogen or a selective estrogen receptor modulator, particularly benzopyran compounds. Pharmaceutical compositions for delivery of active ingredient(s) and kit(s) useful to the invention are also disclosed.
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GADD45BETA TARGETING AGENTS (Thu, 15 Jun 2017)
Compounds based around tetrapeptide, tripeptide and dipeptide moeties and corresponding peptiod moeties. Related methods and pharmaceutical compositions for use in treatment of cancer, inflammatory diseases, and other disorders.
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PYRAZOLYL QUINOXALINE KINASE INHIBITORS (Thu, 15 Jun 2017)
The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.
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METHOD OF TREATING CANCER AND GOLD(III) COMPLEXES AS ANTI-CANCER AGENTS (Fri, 09 Jun 2017)
<p id="p-0001" num="0000">A method for treating cancer and gold(III) complexes with diaminocyclohexane ligand as anticancer agents. Also described are a pharmaceutical composition incorporating the gold(III) complexes and a method of synthesizing the gold(III) complexes.</p>
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SALTS OF CONJUGATES FOR CANCER THERAPY (Fri, 09 Jun 2017)
The present invention relates to pharmaceutically acceptable salts of conjugates comprising a chemotherapeutic drug and an amino acid or a derivative thereof, which are readily taken up by a target cell and reduce side effects induced by the chemotherapeutic drug. In particular, the present invention relates to pharmaceutically acceptable salts of conjugates comprising cytidine analog drugs and aspartic or glutamic acid and analogs thereof, pharmaceutical compositions comprising these conjugates and use thereof for the treatment of cancer or a pre-cancer condition or disorder.
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CYCLING THERAPY USING 3-(5-AMINO-2-METHYL-4-OXO-4H-QUINAZOLIN-3-YL)-PIPERIDINE-2,6-DIONE (Fri, 09 Jun 2017)
Provided herein are methods of treating, preventing and/or managing cancer, including lymphoma, which comprise administering to a patient 3-(5-amino-2-methyl-4- oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione, or an enantiomer or a mixture of enantiomers thereof, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph thereof in a cyclic therapy regimen.
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HETEROCYCLE COMPOUNDS AND USES THEREOF (Fri, 09 Jun 2017)
Compounds having the general formula (I) and pharmaceutical compositions that can be used as Bruton's Tyrosine Kinase (BTK), ITK, JAK3, and selective mutant epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitor and their uses in the treatment of related diseases and disorders such as cancer.
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ANTI-OX40 ANTIBODIES AND METHODS OF USE THEREOF (Fri, 09 Jun 2017)
The present disclosure provides antibodies that specifically bind to human OX40 receptor (OX40) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human OX40 and modulate OX40 activity, e.g., reduce, deactivate, or inhibit OX40 activity. The present disclosure also provides methods for autoimmune or inflammatory diseases or disorders, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., reduces, deactivates, or inhibits OX40 activity.
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SLC45A2 PEPTIDES FOR IMMUNOTHERAPY (Fri, 09 Jun 2017)
Provided are SLC45A2 peptides that bind to MHC I (HLA-A2) on melanoma cells or other antigen-presenting cells and are recognized by T-cell receptors on T cells. The SLC45 A2 peptides may be therapeutically used to treat a cancer, such as a cutaneous melanoma, uveal melanoma, a mucosal melanoma, or a metastatic melanoma. Methods for expanding a population of T cells that target SLC45A2 are also provided.
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3-PYRIMIDINYL PYRROLO [2,3-B] PYRIDINE AS NEW ANTICANCER AGENTS AND THE PROCESS FOR THE PREPARATION THEREOF (Fri, 09 Jun 2017)
The present invention relates to novel 3-pyrimidinyl pyrrolo [2,3-b] pyridine. Particularly, the present invention relates to the preparation of compounds and their anti-cancer activities. More particularly, the present invention relates to new compounds useful as modulators of cyclin-dependent kinase.
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ANTI-OX40 ANTIBODIES AND METHODS OF USE THEREOF (Fri, 09 Jun 2017)
The present disclosure provides antibodies that specifically bind to human OX40 receptor (OX40) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human OX40 and modulate OX40 activity, e.g., enhance, activate, or induce OX40 activity, or diminish, deactivate, or suppress OX40 activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., enhances, activates, or induces OX40 activity. Also provided are methods for treating autoimmune or inflammatory diseases or disorders, by administering an antibody that specifically binds to human OX40 and modulates OX40 activity, e.g., diminishes, deactivates, or suppresses OX40 activity.
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