Cancer

AMINOSTEROID DERIVATIVES AND PROCESS FOR PRODUCING SAME (Fri, 08 Dec 2017)
Estrane-based and androstane-based aminosteroid derivatives are described herein. More specifically, the following piperazinyl-steroid compounds of Formula I, Formula II, Formula III, and Formula IV are described. The compounds display cytotoxicity on a variety of cancer cell lines. A process for producing the compounds and their use in the manufacture of pharmaceutical formulations and/or combinations is also disclosed.
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ANTIBODY-DRUG-CONJUGATES COMPRISING NOVEL ANTHRACYCLINE-DERIVATIVES FOR CANCER TREATMENT (Fri, 08 Dec 2017)
The present invention relates to novel anthracycline derivatives comprising two oxazolidine cycles and the preparation of said anthracycline derivatives. Furthermore, antibody-drug conjugates (ADCs) comprising the novel anthracycline derivatives and the use of such ADCs in the prevention and treatment of cancer are disclosed.
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METHODS AND SYSTEMS FOR METABOLITE AND/OR LIPID-BASED DETECTION OF COLORECTAL CANCER AND/OR ADENOMATOUS POLYPS (Fri, 08 Dec 2017)
Described herein are sets of metabolite and lipid (e.g., fatty acid) markers that can be used in the detection of early stage colorectal cancer and/or early development of adenomatous polyps. Presented herein are illustrative pathology-linked panels. In certain embodiments, the markers presented herein (or subsets thereof) are used as a panel for detecting either colorectal cancer or adenomatous polyps at the same time. The markers presented herein include metabolites and lipids (e.g., fatty acid) freely detectable and accurately quantifiable in human serum. In certain embodiments, the sample may be plasma, urine, saliva, whole blood, dried blood spot or dried serum spot.
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PHOSPHORAMIDATE NUCLEOSIDE DERIVATIVES AS ANTICANCER AGENTS (Fri, 08 Dec 2017)
This invention relates to derivatives of cladribine of Formula (I). The compounds are phosphoramidate derivatives in which the phosphoramidate moiety is situated on the 3'-hydroxyl group of cladribine. The invention also relates to pharmaceutical formulations of the cladribine derivatives and their use in methods of treatment. The compounds are useful in the treatment of cancer.
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ADENOSINE DERIVATIVES FOR USE IN THE TREATMENT OF CANCER (Fri, 08 Dec 2017)
The present invention relates to chemical compounds of formula (I) as defined in the amended claims, their preparation and their use in the treatment of cancer.
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UTTROSIDE B AND DERIVATIVES THEREOF AS THERAPEUTICS FOR HEPATOCELLULAR CARCINOMA (Fri, 08 Dec 2017)
The present invention includes Uttroside B compositions and method for the treatment of hepatocellular carcinoma. Chemotherapeutic options for liver cancer are limited and the prognosis of HCC patients remains dismal. Sorafenib, is the only drug currently available for the treatment of hepatocellular carcinoma.
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HETEROCYCLIC INHIBITORS OF PTPN11 (Fri, 08 Dec 2017)
The present invention relates to compounds which may be useful as inhibitors of PTPN11 for the treatment or prevention of cancer and other PTP-mediated diseases. Disclosed herein are new compounds and compounds based on pyrazolopyrazines and their application as pharmaceuticals for the treatment of disease.
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PENICILLAMINE CONJUGATES AND PARTICLES AND FORMULATIONS THEREOF (Fri, 08 Dec 2017)
Conjugates of an active agent attached to a targeting moiety via a penicillamine linker, and particles comprising such conjugates have been designed. Such conjugates and particles can provide increased stability and improved temporospatial delivery of the active agent, improved biodistribution and penetration in tumor, and/or decreased toxicity. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer.
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IMIDODICARBONIMIDIC DIAMIDE ANALOGS (Fri, 08 Dec 2017)
The present disclosure is directed to imidodicarbonimidic diamide compounds, 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.
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COMPOSITIONS AND METHODS FOR TARGETING AND TREATING HOMOLOGOUS RECOMBINATION-DEFICIENT TUMORS (Fri, 08 Dec 2017)
The invention includes compositions and methods for treating or preventing a cancer in a subject. In one aspect the invention provides methods of administering to a subject suffering from a cancer with cells containing an IDH1 or IDH2 mutation, at least one compound comprising a DNA repair inhibitor. The invention also provides methods of treating a cancer with 2 HG, a derivative of 2-HG, any variant and any mixtures thereof. In one aspect the invention provides a pharmaceutical composition comprising an anti-tumor effective mount of at least one compound selected from the group consisting of 2-hydroxyglutarate (2-HG), a derivative of 2-HG, any variant and any mixtures thereof.
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PHARMACEUTICAL COMPOSITION COMPRISING AN AMIDE DERIVATIVE OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF INHIBITING GROWTH OF CANCER CELLS AND A STABILIZER HAVING LOW MELTING POINT (Fri, 01 Dec 2017)
The present invention relates to a pharmaceutical composition comprising a thienopyrimidine compound, or a pharmaceutically acceptable salt thereof, or a hydrate of a pharmaceutically acceptable salt thereof and one or more low melting point stabilizer(s) inhibiting generation of impurities, and a pharmaceutical dosage form prepared using and comprising the same.
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DIHYDROOXADIAZINE COMPOUNDS FOR TREATING INFECTIONS AND CANCER (Fri, 01 Dec 2017)
The invention relates to the use of l-(4,6-dipentyl-5,6- dihydro-2H-l,2,3-oxadiazin-2-yl)-3-hydroxypropan-l-one in treating and /or preventing infections caused by a bacterium, fungus or virus or in treating and/or preventing cancer. Additionally, the invention relates to a process for obtaining the compound of formula (I) of the invention, said process comprising the steps of cultivating a strain of Dolichospermum sp in an aqueous nutrient medium with assimilable carbon and nitrogen sources and salts, under controlled aerobic conditions, and then recovering the compound of general formula (I) from the culture broth.
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BENZAZEPINE DICARBOXAMIDE COMPOUNDS WITH SECONDARY AMIDE FUNCTION (Fri, 01 Dec 2017)
This invention relates to new benzazepine dicarboxamide compounds of the formula (I) wherein R1 to R4 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are TLR agonists and may therefore be useful as medicaments for the treatment of diseases such as cancer, autoimmune diseases, inflammation, sepsis, allergy, asthma, graft rejection, graft-versus-host disease, immunodeficiencies, and infectious diseases.
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BENZAZEPINE DICARBOXAMIDE COMPOUNDS WITH TERTIARY AMIDE FUNCTION (Fri, 01 Dec 2017)
This invention relates to new benzazepine dicarboxamide compounds of the formula (I) wherein R1 to R 3 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are TLR agonists and may therefore be useful as medicaments for the treatment of diseases such as cancer, autoimmune diseases, inflammation, sepsis, allergy, asthma, graft rejection, graft-versus-host disease, immunodeficiencies, and infectious diseases.
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TRICYCLIC HETEROCYLIC DERIVATIVES (Fri, 01 Dec 2017)
Compounds of the formula (I) in which R1 and R2 have the meanings indicated in Claim 1,are inhibitors of ATR, and can be employed for the treatment of diseases such as cancer.
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3-OXO-2,6-DIPHENYL-2,3-DIHYDROPYRIDAZINE-4-CARBOXAMIDES (Fri, 01 Dec 2017)
The present invention covers 3-oxo-2,6-diphenyl-2,3-dihydropyridazine-4-carboxamide compounds of general formula (I): in which R1, R2, R3, R4, R5 and R6 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer or conditions with 10 dysregulated immune responses or other disorders associated with aberrant AHR signaling, as a sole agent or in combination with other active ingredients.
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AGENTS FOR MODULATION OF WNT-TCF SIGNALLING AND USES THEREOF (Fri, 01 Dec 2017)
The present invention relates to inhibitors of WNT-TCF signalling and compositions thereof. The invention further relates to use of those inhibitors of WNT-TCF signalling and compositions thereof for the treatment and/or prevention and/or prevention of recurrence of a WNT-activated cancer and/or a cancer associated with the cancer stem cells.
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MOLECULAR PROBES FOR DETECTION AND IMAGING OF PANCREATIC CANCER (Fri, 01 Dec 2017)
Molecular probes for detecting and imaging pancreatic cancer are disclosed. The probes are modified benzoxanthene fluorophores, which are selectively taken up by pancreatic cancer cells, such as pancreatic ductal adenocarcinoma cells. Embodiments of the disclosed probes are useful for pancreatic cancer detection, therapeutic monitoring, and/or image-guided surgery.
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PEGYLATED CARFILZOMIB COMPOUNDS (Fri, 01 Dec 2017)
The present invention provides polymeric pegylated carfilzomib compounds, and pharmaceutically acceptable salts thereof, of Formula I wherein R1, R2, linker, PEG, n and o are as defined herein. The invention also provides methods of making and using these compounds to treat cancer, and particularly to treat hematological malignancies including multiple myeloma.
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METHODS OF TREATING CANCER WITH A PSMA LIGAND-TUBULYSIN COMPOUND (Fri, 01 Dec 2017)
The invention described herein pertains to drug delivery conjugates for targeted therapy. The invention described herein relates to methods of treating PSMA expressing cancers with a PSMA ligand-tubulysin compound. The invention described herein also relates to methods of treating PSMA-expressing cancers with a PSMA ligand-tubulysin compound in patients where stable disease results after treatment with the PSMA ligand-tubulysin compound.
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EGFR INHIBITOR COMPOUNDS (Fri, 01 Dec 2017)
Disclosed herein are nitrogen-containing bicyclic compounds, together with pharmaceutical compositions and methods of ameliorating and/or treating a cancer described herein with one or more of the compounds described herein.
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PYRAZOLOPYRIDINE DERIVATIVES FOR THE TREATMENT OF CANCER (Fri, 01 Dec 2017)
The present invention relates to a compound formula (I): and to salts thereof, wherein R1, R2X, and Y have any of the values defined herein, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders such as cancer, inflammatory disorders and autoimmune diseases.
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ESTROGEN RECEPTOR MODULATOR COMBINATIONS (Fri, 01 Dec 2017)
Described herein, inter alia, are compositions and methods for treating or preventing hyperproliferative disorders, including cancer.
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METHOD OF TREATING CANCER BY TARGETING MYELOID-DERIVED SUPPRESSOR CELLS (Fri, 01 Dec 2017)
The invention described herein relates to methods for treating a cancer using one or more compounds comprising a folate receptor binding ligand attached to a drug via a linker. More particularly, the invention described herein relates to methods for treating a cancer using one or more compounds comprising a folate receptor binding ligand attached to a drug via a linker to target myeloid-derived suppressor cells.
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INHIBITORS OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE (Fri, 01 Dec 2017)
Disclosed herein are inhibitors of IRAK protein kinase. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the IRAK inhibitors are described, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.
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INHIBITORS OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE (Fri, 01 Dec 2017)
Disclosed herein are inhibitors of IRAK protein kinase of formula (I). Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the IRAK inhibitors are described, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.
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INHIBITORS OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE (Fri, 01 Dec 2017)
Disclosed herein are inhibitors of IRAK protein kinase of formula (I). Also disclosed are pharmaceutical compositions that include the compounds of formula (I). Methods of using the IRAK inhibitors are described, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions. Formula (I)
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CALLYSPONGIOLIDE, ANALOGS THEREOF AND USES THEREOF (Fri, 01 Dec 2017)
Described herein are compounds of the formula (I)-(III) (or a pharmaceutically acceptable salt, polymorph, prodrug, solvate or clathrate thereof), as well as methods of making and using compounds of the formula (I)-(III) to, among other things, treat various forms of cancer.
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HETEROCYCLIC INHIBITORS OF CBP/EP300 AND THEIR USE IN THE TREATMENT OF CANCER (Fri, 01 Dec 2017)
The present invention relates to compounds of formula (I) and formula (II): and to salts thereof, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) of formula (II), or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders such as cancer, inflammatory disorders and autoimmune diseases.
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PROCESS FOR THE MANUFACTURE OF 6-ALKYNYL-PYRIDINE DERIVATIVES (Fri, 24 Nov 2017)
The application includes a description of novel intermediates, of new manufacturing steps resulting in a novel and improved process for producing the intermediates and the final compounds, i.e., 6-alkynyl-pyridine derivatives. The intermediates of the invention are useful to produce 6-alkynyl-pyridine derivatives, which compounds are useful for the treatment of cancer.
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DERIVATIVES OF LIMONOIDS FOR TREATING AND/OR PREVENTING GROWTH OF BREAST CANCER CELLS (Fri, 24 Nov 2017)
The present invention relates to new compounds derivatives of limonoids for treating and/or preventing growth of cancer cells, particularly for treating the breast cancer. Breast cancer is cancer that develops from breast tissue. It is the most common invasive cancer in women. The inventors have now discovered new derivatives of type limonoid, which possess a powerful anticancer activity, with, at the same time, low toxicity. They have demonstrated that these novel derivatives are efficient against breast cancer cell lines. In particular, the present invention relates to compounds of formula (I) for use for treating the breast cancer. Particularly, the inventors tested the compounds on cell line MDA-MB-468, and in particular, the impact of the compounds on mitotic phase and on cell death in cancer cells have been analysed.
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BIOORTHOGONAL COMPOUNDS COMPRISING A PROPARGYL GROUP FOR TREATING CANCER (Fri, 24 Nov 2017)
A method of preparing an active agent or a salt thereof from a prodrug first compound (1) comprising a propargyl group connected to an oxygen that is directly or indirectly connected to the active agent is provided, wherein the bond between the propargyl group and the oxygen is cleaved by reacting the first compound with palladium or gold, thereby releasing the active agent. Prodrug compositions suitable for use in the method are also provided.
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BENZAMIDE COMPOUNDS AS ROR GAMMA MODULATORS (Fri, 24 Nov 2017)
The present disclosure is directed to compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein ring A, R1, R2, R3, R4, R5, n and p 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.
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RUTHENIUM-SPHINGOMYELIN COMPLEXES AND METHODS FOR THEIR USE IN THE TREATMENT OF TUMORS (Fri, 24 Nov 2017)
The described invention provides a compound comprising an organometallic complex comprising a core of ruthenium and sphingomyelin, with the option of added zinc, that, in a therapeutic amount, through further connections with contributing organic ligands, are effective as chemotherapeutic agents that have an anti-tumor or anti-cancer effect on a tumor comprising tumor cells including a cytotoxic effect on of the tumor cells, inhibition of the growth of the tumor comprising the tumor cells, inhibition of migration of the tumor cells, or any combination of these effects.
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NOVEL CYCLOSPORIN DERIVATIVES AND USES THEREOF (Fri, 24 Nov 2017)
A compound of the Formula (I) is disclosed: (I) or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification. Also described are a pharmaceutical composition comprising the same and a method for treating or preventing viral infections, inflammation, dry eye, central nervous disorders, cardiovascular diseases, cancer, obesity, diabetes, muscular dystrophy, lung, and liver, and kindey diseases, and hair loss using the same.
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OXOINDOLINE DERIVATIVES AS PROTEIN FUNCTION MODULATORS (Fri, 24 Nov 2017)
The present invention provides chimeric compounds of formula (II) that modulate protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, TNF-alpha activity, CKl-alpha activity and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of protein-mediated diseases, disorders, and conditions, such as cytokine-mediated diseases, disorders, and conditions, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, organ transplant rejection, and cancer, are provided.
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CATIONIC SULFONAMIDE AMINO LIPIDS AND AMPHIPHILIC ZWITTERIONIC AMINO LIPIDS (Fri, 24 Nov 2017)
The present disclosure provides one or more amino lipids such as an amino lipids containing a sulfonic acid or sulfonic acid derivative of the formulas: Formula (I) or (IV) wherein the variables are as defined herein. These amino lipids may be used in compositions with one or more helper lipids and a nucleic acid therapeutic agent. These compositions may be used to treat a disease or disorder such as cancer, cystic fibrosis, or other genetic diseases.
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COMPOSITIONS AND METHODS FOR THE EXPRESSION OF EUKARYOTIC OLIGOSACCHARIDES ON BACTERIAL OUTER MEMBRANE VESICLES (Fri, 24 Nov 2017)
The present invention relates to a method of displaying an antigen with a eukaryotic carbohydrate component. The method involves providing a bacterial cell transformed with a nucleic acid construct encoding an antigen with a eukaryotic carbohydrate component and culturing the transformed bacterial cell under conditions effective to express the antigen with a eukaryotic carbohydrate component, associate the expressed antigen with a eukaryotic carbohydrate component and a lipid A core carbohydrate in the bacterial cell to form a lipo-carbohydrate complex, and display the lipo-carbohydrate complex on the surface of the bacterial cell. Also disclosed are a bacterial cell or a vesicle displaying on its outer surface a lipo-carbohydrate complex of an antigen with a eukaryotic carbohydrate component associated with a lipid A core carbohydrate as well as an antibody which recognizes the eukaryotic carbohydrate component of the bacterial cell or vesicle. The vesicle or antibody can be administered to a subject to raise an immune response against pathogen infection, to treat disease, or to treat cancer.
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NOVEL MITOCHONDRIAL UNCOUPLERS FOR TREATMENT OF METABOLIC DISEASES AND CANCER (Fri, 24 Nov 2017)
The present disclosure relates to benzamide compounds, prodrugs of the compounds, pharmaceutical compositions containing the compounds and/or the prodrugs and methods of using the compounds, prodrugs and pharmaceutical compositions in the treatment of diseases related to lipid metabolism including diabetes, Non-Alcholic Fatty Liver Disease (NAFLD), Non-Alcholic Steathohepatitis (NASH), diseases caused by abnormal cell proliferation including cancer, psoriasis, and infectious diseases.
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MRNA COMBINATION THERAPY FOR THE TREATMENT OF CANCER (Fri, 24 Nov 2017)
The present disclosure relates to the use of nucleic acid (e.g., mRNA) combination therapies for the treatment of cancer. The disclosure provides compositions, and methods for their preparation, manufacture, and therapeutic use, wherein those compositions comprise at least two polynucleotides (e.g., mRNAs) in combination wherein the at least two polynucleotides are selected from the group consisting of (i) a polynucleotide encoding an immune response primer (e.g., IL23), (ii) a polynucleotide encoding an immune response co-stimulatory signal (e.g., OX40L), (iii) a polynucleotide encoding a checkpoint inhibitor (e.g., an anti CTLA-4 antibody), and, (iv) a combination thereof. The therapeutic methods disclosed herein comprise, e.g., the administration of a combination therapy disclosed herein for the treatment of cancer, e.g., by reducing the size of a tumor or inhibiting the growth of a tumor, in a subject in need thereof. In some aspects, the combination therapies disclosed herein disclosed are administered intratumorally.
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NANOPARTICLES FOR CHEMOTHERAPY, TARGETED THERAPY, PHOTODYNAMIC THERAPY, IMMUNOTHERAPY, AND ANY COMBINATION THEREOF (Fri, 24 Nov 2017)
Prodrugs containing lipid moieties attached to drug derivatives, such as anti-cancer drug derivatives, via linkers comprising disulfide groups are described. Also described are nanoparticles coated with a lipid layer containing the prodrugs, formulations comprising the nanoparticles, and the use of the nanoparticles in methods of treating diseases, such as cancer, alone or in combination with additional drug compounds, targeting agents, and/or immunotherapy agents, such as immunosuppression inhibitors that target the CTLA-4, PD-1/PD-L1, IDO, LAG-3, CCR-7 or other pathways, or multiple immunosuppression inhibitors targeting a combination of such pathways. Optionally, the nanoparticles can comprise a photosensitizer or a derivative thereof and can be used in methods involving photodynamic therapy. Synergistic therapeutic effects result from combinations of multiple modalities provided by the disclosed nanoparticles and/or nanoparticle formulations.
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Inhibitors of indoleamine 2,3-dioxygenase for the treatment of cancer (Fri, 24 Nov 2017)
There are disclosed compounds of formula (I) that modulate or inhibit the enzymatic activity of indoleamine-2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the invention.
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Inhibitors of indoleamine 2,3-dioxygenase for the treatment of cancer (Fri, 24 Nov 2017)
There are disclosed compounds of formula (I) that modulate or inhibit the enzymatic activity of indoleamine-2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the invention.
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Inhibitors of indoleamine 2,3-dioxygenase for the treatment of cancer (Fri, 24 Nov 2017)
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.
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PD-L1 promoter methylation in cancer (Fri, 24 Nov 2017)
This invention provides methods for the treatment of cancer in subjects having medium or low methylation level in the PD~L1 promoter region. Also provided are related kits and articles of manufacture.
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Salts and prodrugs of 1-methyl-D-tryptophan (Fri, 24 Nov 2017)
Presently provided are indoximod prodrug and salt compounds and pharmaceutical compositions comprising salts and prodrugs of indoximod, that produce enhanced plasma concentration and exposure to indoximod compared to direct administration of indoximod, in patients in need of treatment of immunosuppression mediated by the indoleamine-2,3-dioxygenase pathway, such as patients with cancer or chronic infectious diseases.
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Benzazepine dicarboxamide compounds (Wed, 22 Nov 2017)
<p id="p-0001" num="0000">This invention relates to novel benzazepine dicarboxamide compounds of the formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.54mm" wi="61.72mm" file="US09822065-20171121-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein R<sup>1 </sup>to R<sup>4 </sup>are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are TLR agonists and may therefore be useful as medicaments for the treatment of diseases such as cancer, autoimmune diseases, inflammation, sepsis, allergy, asthma, graft rejection, graft-versus-host disease, immunodeficiencies, and infectious diseases.</li> </ul> </li> </ul> </p>
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Substituted spirooxindoles (Wed, 22 Nov 2017)
<p id="p-0001" num="0000">The substituted spirooxindoles are MDM2-p53 inhibitors bearing a benzylidine (styryl) arm and have a complex fused ring system ideally suited for binding to the MDM2 protein, thereby interrupting its protein-protein interaction (PPI). Sixteen compounds, designated 4a-4p, were synthesized in a simple smooth method using an asymmetric 1,3-dipolar reaction as the key step. Testing showed that the compounds exhibit anti-cancer activity against various forms of cancer cells affecting humans.</p>
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NEW COMPOUNDS AND PHARMACEUTICAL USE THEREOF IN THE TREATMENT OF CANCER (Fri, 17 Nov 2017)
The present invention relates to a compound or a pharmaceutical salt thereof comprising a hexapeptide sequence of formula (I), its method of synthesis and its use in anticancer therapy. The invention also relates to a pharmaceutical composition for use in the treatment of cancer comprising at least one soluble peptide according to the invention or at least one acid nucleic according to the invention or at least one expression vector according to the invention, or at least one host cell according to the invention and a pharmaceutically acceptable carrier.
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IMIDAZO[4,5-C]QUINOLIN-2-ONE COMPOUNDS AND THEIR USE IN TREATING CANCER (Fri, 17 Nov 2017)
The specification generally relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof, where R1 is 4-fluoropiperidin-1-yl or 3-fluoropyrrolidin-1-yl and R2 is methyl or hydro; the use of compounds of Formula (I) or pharmaceutically acceptable salts thereof to treat or prevent ATM mediated disease, including cancer; pharmaceutical compositions comprising substituted imidazo[4,5- c]quinolin-2-one compounds or pharmaceutically acceptable salts thereof; kits comprising compounds of Formula (I) or pharmaceutically acceptable salts thereof; methods of manufacture of compounds of Formula (I) or pharmaceutically acceptable salts thereof; and intermediates useful in such manufacture.
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ASSAY (Fri, 17 Nov 2017)
The invention relates to the use of certain ferrous iron, 2-oxoglutarate dependent oxygenases acting on post-translationally modified arginine residues, in particular those modified by methylation, and assays for these enzymes,in order to discover molecules altering the activity of the 2-oxoglutarate oxygenases, which can be used in the treatment of diseases including cancer.
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SMALL MOLECULE N-(ALPHA-PEROXY) CARBAZOLE COMPOUNDS AND METHODS OF USE (Fri, 17 Nov 2017)
The invention relates to novel N-(α-peroxy)carbazole compounds of Formula I and methods for use. (I) The N-(α-peroxy)carbazole compounds described herein are useful for treating or preventing parasitic infections, bacterial infections, and cancer in subjects. The methods include administering an N-(α-peroxy)carbazole compound as described herein to a subject. Also described herein are methods for synthesizing N-(α-peroxy)carbazole compounds.
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INDOLE AND INDAZOLE CYANOCINNAMATE COMPOUNDS AND THERAPEUTIC USES THEREOF (Fri, 17 Nov 2017)
Disclosed are Indole and Indazole cyanocinnamate compounds, method for preparing these compounds, and methods for treating cancer.
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CONVERGENT AND ENANTIOSELECTIVE TOTAL SYNTHESIS OF COMMUNESIN ANALOGS (Fri, 17 Nov 2017)
A highly convergent biomimetic synthesis of a complex polycyclic scaffold has been successfully implemented. From these efforts, compounds having a structure of Formula (I) or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1-R8 and m, n, r, s, t, and u are as defined herein, is provided. Methods of making such compounds are also disclosed as are methods for the treatment of cancer, various infectious diseases, and abnormal cardiovascular function.
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MODULATORS OF P97 AAA ATPASE ACTIVITY (Fri, 17 Nov 2017)
The present invention is directed to methods of inhibiting or modulating p97 and compounds and compositions useful in such methods. Diseases and conditions that can be treated with the compounds and compositions of the invention include, but are not limited to, cancer and neurodegenerative disorders susceptible to treatment by modulation or inhibition of p97.
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YAP1 INHIBITORS AND METHODS (Fri, 17 Nov 2017)
YAP1 inhibitors and methods of treating a subject with a cancer that include administering a YAP1 inhibitor are disclosed. Also disclosed are methods for determining responsiveness to a YAP1 inhibitor in a subject, methods for diagnosing a tumor in a subject including determining the level of YAP1 expression, compositions that include YAP1 inhibitors, and methods of using those compositions.
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PHOSPHOTIDYLINOSITOL 3-KINASE INHIBITORS (Fri, 17 Nov 2017)
This disclosure relates to phosphoinositide 3-kinases (PI3Ks) inhibitors such as N-(5-(imidazo[1,2-a]pyridin-6-yl)pyridin-3-yl)sulfonamide derivatives and uses related thereto. In certain embodiments, the disclosure relates to methods of treating PI3K associated diseases or conditions comprising administering an effective amount of a compound disclosed herein to a subject in need thereof. In certain embodiments, the subject is at risk of, exhibiting symptoms of, suffering from, or diagnosed with cancer or a hematological malignancy.
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METHODS AND COMPOSITIONS FOR TREATING ADVANCED STAGE NON-SMALL CELL LUNG CANCER (Fri, 17 Nov 2017)
The present invention provides methods and compositions for treating advanced stage non-small cell lung cancer by cyclohexenone compounds.
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SMALL MOLECULE N-(ALPHA-PEROXY) INDOLE COMPOUNDS AND METHODS OF USE (Fri, 17 Nov 2017)
The invention relates to novel N-(α-peroxy)indole compounds of Formula I and methods for use. (I) The N-(α-peroxy)indole compounds described herein are useful for treating or preventing parasitic infections, bacterial infections, and cancer in subjects. The methods include administering an N-(α-peroxy)indole compound as described herein to a subject. Also described herein are methods for synthesizing N-(α-peroxy )indole compounds.
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COMBINATION THERAPY FOR TREATING CANCER (Fri, 17 Nov 2017)
The present invention relates to compositions comprising inhibitors of human histone methyltransferase EZH2 and one or more other therapeutic agents, particularly anticancer agents such as prednisone, and methods of combination therapy for administering to subjects in need thereof for the treatment of cancer.
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(HETERO)ARYL CYCLOPROPYLAMINE COMPOUNDS AS LSD1 INHIBITORS (Fri, 17 Nov 2017)
The invention relates to (hetero)aryl cyclopropylamine compounds, including particularly the compounds of formula I as described and defined herein, and their use in therapy, including, e.g., in the treatment or prevention of cancer, a neurological disease or condition, or a viral infection.
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FUNCTIONALISED AND SUBSTITUTED INDOLES AS ANTI-CANCER AGENTS (Fri, 17 Nov 2017)
ABSTRAC The present iventio n reats to attrmysi compouds processes for thei preparation, and rethods for treating or prevertng a disease r dsorder, such as a proierative disease (preferably cancer), using compounds of the invention.
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ADENINE DERIVATIVES AS PROTEIN KINASE INHIBITORS (Fri, 10 Nov 2017)
The present invention relates to a compound suitable for use as a kinase inhibitor according to general formula (I) [compound (C), herein after], or the N- oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof, formula (I) wherein A, R1, R2, R3, R3', R4, R4', X, Y, Z, T are as defined in the claims. The invention further relates to an in vitro method of inhibiting protein kinase activity which comprises contacting a protein kinase with a compound of formula (I), or the N-oxide, pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or stereoisomer thereof. The invention further relates to the compounds of formula (I) per se, as well as to their use as a medicament, and for use or in a method of treatment of a disease mediated by a protein kinase selected from cancer, inflammatory disorders, cardiovascular diseases, viral induced diseases, circulatory diseases, fibro-proliferative diseases and pain sensitization disorders.
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SUBSTITUTED 2, 4-DIAMINO-QUINOLINE DERIVATIVES FOR USE IN THE TREATMENT OF PROLIFERATIVE DISEASES (Fri, 10 Nov 2017)
This application discloses compounds according to generic Formula (I): wherein all variables are defined as described herein which exhibit strong inhibition effects on various cancer cell lines. The compounds disclosed herein are useful for the treatment of proliferative diseases, including neoplastic diseases such as cancer and non- neoplastic disorders such as rheumatoid arthritis. Also disclosed are pharmaceutical compositions containing compounds of Formula (I) and at least one carrier, diluent or excipient and optionally one or more additional therapeutically active agents, including anticancer agents. This application also discloses methods for treating a proliferative disease, including neoplastic diseases such as cancer and non- neoplastic disorders such as rheumatoid arthritis.
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PIPERIDINES AS MENIN INHIBITORS (Fri, 10 Nov 2017)
The present disclosure provides compounds represented by Formula (I): (Formula(I)) and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R2, R3a, R3b, A, G, X, and Y are as defined as set forth in the specification. The present disclosure also provides compounds of Formula (I) for use to treat a condition or disorder responsive to menin inhibition such as cancer.
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NANOPARTICLE CONJUGATES OF HIGHLY POTENT TOXINS AND INTRAPERITONEAL ADMINISTRATION OF NANOPARTICLES FOR TREATING OR IMAGING CANCER (Fri, 10 Nov 2017)
Disclosed are methods of treating cancer of the intraperitoneal cavity using compositons comprising nanoparticles without targeting agents. In addition, nanoparticles are described that comprise a highly toxic anticancer agent (e.g., an anticancer agent having an IC50 less than 1 nM) covalently bound via a linker to a triblock copolymer. Other nanoparticles that comprise Pt(IV) and an anticancer agent are also described. Also disclosed are nanoparticles comprising imaging agents non-covalently associated with a polymer, and methods of imaging cancer of the intraperitoneal cavity using compositons comprising nanoparticles without targeting agents.
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INHIBITORS OF IRES-MEDIATED PROTEIN SYNTHESIS (Fri, 10 Nov 2017)
This disclosure relates to inhibitors of IRES-mediated protein synthesis, compositions comprising therapeutically effective amounts of these compounds, and methods of using those compounds and compositions in treating hyperproliferative disorders, e.g., cancers. This disclosure also relates to compositions comprising inhibitors of IRES-mediated protein synthesis and mTOR inhibitors, and to methods of treating cancer by conjoint administration of inhibitors of IRES-mediated protein synthesis and mTOR inhibitors.
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INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF THEIR USE (Fri, 10 Nov 2017)
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.
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INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF THEIR USE (Fri, 10 Nov 2017)
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.
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INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF THEIR USE (Fri, 10 Nov 2017)
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.
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INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF THEIR USE (Fri, 10 Nov 2017)
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.
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INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF THEIR USE (Fri, 10 Nov 2017)
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.
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HETEROCYCLIC COMPOUNDS AS IMMUNOMODULATORS (Fri, 10 Nov 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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Deuterium-enriched isoindolinonyl-piperidinonyl conjugates and oxoquinazolin-3(4H)-yl-piperidinonyl conjugates and methods of treating medical disorders using same (Wed, 08 Nov 2017)
<p id="p-0001" num="0000">The invention provides deuterium-enriched isoindolinonyl-piperidinonyl conjugates, deuterium-enriched oxoquinazolin-3(4H)-yl-piperidinonyl conjugates, pharmaceutical compositions, and methods of using such conjugates and pharmaceutical compositions to treat cancer, angiogenesis disorders, immune disorders, and other medical disorders.</p>
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NEW SALT OF ABEXINOSTAT, ASSOCIATED CRYSTALLINE FORM, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM (Fri, 03 Nov 2017)
<p id="p-0001" num="0000">Abexinostat tosylate of formula (II):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="47.84mm" wi="76.20mm" file="US20170313671A1-20171102-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and its crystalline form I characterised by its X-ray powder diffraction diagram, its Raman spectrum and its solid-state <sup>13</sup>C CP/MAS NMR spectrum.</p> <p id="p-0004" num="0000">Medicinal products containing the same which are useful in the treatment of cancer.</p>
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METHOD OF ISOLATING PHENANTHROINDOLIZIDINE ALKALOIDS FROM TYLOPHORA ATROFOLLICULATA WITH HIF-1 INHIBITORY ACTIVITY, COMPOSITIONS COMPRISING THEM AND THEIR USE (Fri, 03 Nov 2017)
<p id="p-0001" num="0000">A method of isolating at least one phenanthroindolizidine alkaloid, in particular with HIF-1 inhibitory activity, from <i>Tylophora atrofolliculata </i>is used to isolate and obtain for example about 22 phenanthroindolizidine alkaloids, including at least 11 new phenanthroindolizidine alkaloids which have not been previously isolated. Experimental tests confirmed an exceptional HIF-1 inhibitory activity of the phenanthroindolizidine alkaloids isolated. A pharmaceutical composition includes at least one phenanthroindolizidine alkaloid and at least one pharmaceutical tolerable excipient. A method of treating a subject suffering from cancer includes administering at least one phenanthroindolizidine alkaloid isolated from <i>Tylophora atrofolliculata</i>. A method of treating a subject suffering from cancer includes administering at least one phenanthroindolizidine alkaloid to the subject.</p>
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SALTS OF LENVATINIB (Fri, 03 Nov 2017)
The present invention relates to solid forms of 4-[3-chloro-4- (cyclopropylcarbamoylamino)phenoxy]-7-methoxy-quinoline-6-carboxamide (CAS No.417716-92-8) of formula I, known as lenvatinib, with an acid that is selected from the group consisting of phosphoric acid, tartaric acid, citric acid, camphorsulfonic acid, isethionic acid and naphthalenedisulfonic acid. Other objects are preparation methods of a salt of lenvatinib with the above mentioned acids and its use in a drug form. The drug with the name Lenvima, which contains lenvatinib mesylate, has been approved by the Food and Drug Administration (FDA) for the treatment of locally recurrent or metastatic, progressive thyroid cancer, resistant to radioactive iodine.
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PIPERIDINYL DERIVATIVES (Fri, 03 Nov 2017)
Compounds of the formula (I) in which X, Y, R1 and R2 have the meanings indicated in Claim 1, are inhibitors of pyruvate dehydrogenase kinase (PDHK), and can be employed, inter alia, for the treatment of diseases such as cancer.
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ANTAGONISTS OF THE THYROID-STIMULATING HORMONE RECEPTOR (TSHR) (Fri, 03 Nov 2017)
The invention relates to chemical compounds that are useful in the treatment of a subject afflicted by a thyroid disease, in particular to compounds that exhibit activity as thyroid-stimulating hormone receptor (TSHR) antagonists and their use in the treatment of hyperthyroidism, Graves' disease, Graves' Ophthalmopathy and thyroid cancer.
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PYRROLOBENZODIAZEPINE CONJUGATES AND THEIR USE FOR THE TREATMENT OF CANCER (Fri, 03 Nov 2017)
A conjugate of formula (I): L -(DL)p, wherein L is a Ligand unit, D is a Drug Linker unit of formula (II), wherein p is an integer of from 1 to 20.
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NANOEMULSIONS AND METHODS FOR CANCER THERAPY (Fri, 03 Nov 2017)
An oxysterol or oxysterol-like compound is provided, which finds use in treating and/or targeting cancer.
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MOFEZOLAC DERIVATIVES AS MULTI-FUNCTIONS SELECTIVE COX-1 INHIBITORS (Fri, 03 Nov 2017)
The invention relates to a new class of compounds of formula (I) targeting COX-1. The invention also relates to the use of some of such compounds as a tool to investigate the structure and function of the enzyme, in the treatment targeting COX-1 or detection of COX-1 in relating disorders or diseases such as cancer and neuroinflammation, in particular in neurological (e.g. autism spectrum disorders) and neurodegenerative diseases (e.g. Alzheimer's diseases, Parkinson's diseases, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), traumatic brain injury (TBI), HIV dementia and prion diseases), and in gynecological tumour (e.g. ovarian cancer), neck and head tumor, and haematological tumours (e.g. multiple myeloma) and in the detection of COX-1 in "in vitro" (cells and tissues) and in "in vivo".
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QUINAZOLINE DERIVATIVE OR ITS SALT AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME (Fri, 03 Nov 2017)
The present invention provides a quinazoline derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, a pharmaceutical composition comprising the same and a use thereof. The quinazoline derivative or its pharmaceutically acceptable salt has a selective inhibitory activity against the phosphatidylinositol 3-kinase delta subunit, and therefore can be usefully applied for preventing or treating cancer, along with avoiding side effects such as lymphopenia-associated inflammatory responses.
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MODIFIED PIGMENT EPITHELIUM-DERIVED FACTOR (PEDF) PEPTIDES AND USES THEREOF FOR TREATING NEOVASCULAR DISEASES, INFLAMMATORY DISEASES, CANCER, AND FOR CYTOPROTECTION (Fri, 03 Nov 2017)
Disclosed are modified pigment epithelium-derived factor (PEDF) peptides, particulate carrier prodrugs thereof, and pharmaceutical compositions comprising the peptides or particulate carrier prodrugs. The peptides, particulate carrier prodrugs, and pharmaceutical compositions may be used to treat diseases and disorders that are amenable to treatment with anti-angiogenic agents, anti-tumorigenic agents, anti- fibrotic agents, chemotherapy-protecting agents, and immune stimulating agents.
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ISOQUINOLIN-3-YL CARBOXAMIDES AND PREPARATION AND USE THEREOF (Fri, 03 Nov 2017)
Isoquinoline compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an isoquinoline compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease, inflammation, auto-immune diseases and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as neurological conditions/disorders/diseases linked to overexpression of DYRK1A.
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ISOQUINOLIN-3-YL CARBOXAMIDES AND PREPARATION AND USE THEREOF (Fri, 03 Nov 2017)
Isoquinoline compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an isoquinoline compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.
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METHODS FOR TREATMENT OF RESISTANT CANCER (Fri, 03 Nov 2017)
The present disclosure describes a method to treat conditions, including cancer, using compounds that can target resistant cancer cells. The compounds of the invention can decrease the rate of proliferation of drug-resistant cancer cells, such as glioma, lung cancer, and uterine sarcoma.
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1,5-DISUBSTITUTED 1,2,3-TRIAZOLES ARE INHIBITORS OF RAC/CDC42 GTPASES (Fri, 03 Nov 2017)
Compounds are disclosed that inhibit RhoGTPases that are useful for inhibiting hyperprofilerative and neoplastic diseases. Specifically, the compounds inhibit the GTPases Rac and Cdc42 that are overactive or overexpressed in signaling pathways in cancer and metastasis. Methods for treatment of cancer and hyperproliferative diseases are disclosed.
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ALKYNE CONTAINING NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO (Fri, 03 Nov 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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OLIGONUCLEOTIDE CONJUGATES AND USES THEREOF (Fri, 03 Nov 2017)
Oligonucleotide conjugates and uses thereof are provided. Aspects of the subject oligonucleotide conjugates include a targeting component, a linker component, a cleavage component, and an oligonucleotide component. The oligonucleotide comprises an identifier sequence or a first and second identifier sequence, allowing for detection and quantification of a target using methods such as next generation sequence and quantitative PCR. Methods of making and using the oligonucleotide conjugates in the diagnosis, prevention and/or treatment of cancer and other diseases are also provided.
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DI-SUBSTITUTED PYRAZOLE COMPOUNDS FOR THE TREATMENT OF DISEASES (Fri, 03 Nov 2017)
Provided herein are compounds, pharmaceutical compositions comprising the compounds, and methods of using the compounds and compositions in treating a condition, disease, or disorder associated with abnormal activation of the SREBP pathway, including metabolic disorders such as obesity, cancer, cardiovascular disease, and nonalcoholic fatty liver disease (NAFLD) wherein the compound is according to Formula (I).
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SIGMA RECEPTOR BINDERS (Fri, 03 Nov 2017)
Provided herein, inter alia, are compounds and methods of treating diseases including cancer, neurological disease, alcohol withdrawal, depression and anxiety, traumatic brain injury, and neuropathic pain.
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SIGMA RECEPTOR BINDERS (Fri, 03 Nov 2017)
Provided herein, inter alia, are compounds and methods of treating diseases including cancer, neurological disease, alcohol withdrawal, depression and anxiety, and neuropathic pain.
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NUCLEAR RECEPTOR MODULATORS AND THEIR USE FOR THE TREATMENT AND PREVENTION OF CANCER (Fri, 03 Nov 2017)

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COMPOSITIONS OF PROTEIN RECEPTOR TYROSINE KINASE INHIBITORS (Fri, 03 Nov 2017)
The present invention relates to novel synthetic substituted heterocyclic compounds and pharmaceutical compositions containing the same that are capable of inhibiting or antagonizing a family of receptor tyrosine kinases, Tropomysosin Related Kinases (Trk), in particular the nerve growth factor (NGF) receptor, TrkA. The invention further concerns the use of such compounds in the treatment and/or prevention of pain, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, or a disease, disorder or injury relating to dysmyelination or demyelination or the disease or disorder associated with abnormal activities of NGF recptor TrkA.
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NOVEL CRYSTALLINE SALT FORMS OF 3-(1,2,4-TRIAZOLO[4,3-A]PYRIDINE-3-YLETHYNYL)-4-METHYL-N-(4-((4-METHYLPIPERAZIN-1-YL)METHYL)-3-TRIFLUOROMETHYLPHENYL)BENZAMIDE FOR MEDICAL APPLICATION (Fri, 27 Oct 2017)
The invention relates to the organic chemistry, pharmacology and medicine, and concerns the prevention and treatment of human and animal diseases associated with the disruption of the activity of various kinases, in particular Abl kinase, for example diseases such as leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, acute lymphocytic leukemia, breast cancer, non-small cell lung cancer, gastrointestinal stromal tumors, ovarian cancer, lymphoma, using a new salt form of 3-(1,2,4-triazolo[4,3-a]pyridine-3-ylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-trifluoromethylphenyl)benzamide. The salt of this compound with methanesulfonic acid, formula (I), or its hydrate, solvate, as well as polymorphic modifications that have the ability to inhibit the activity of kinases, in particular Abl kinases. The present invention also relates to pharmaceutical compositions comprising a therapeutically effective amount of a salt of the invention, to a method for preparing a crystalline salt of the invention, as well as to a method for treating oncological diseases in a subject.
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INDAZOLE DERIVATIVES FOR USE IN DOWN-REGULATION OF THE ESTROGEN RECEPTOR FOR THE TREATMENT OF CANCER (Fri, 27 Oct 2017)
The specification relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof. The specification also relates to processes and intermediates used for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.
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INDAZOLE DERIVATIVES THAT DOWN-REGULATE THE ESTROGEN RECEPTOR AND POSSESS ANTI-CANCER ACTIVITY (Fri, 27 Oct 2017)
The specification relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof. The specification also relates to processes and intermediates used for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.
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MACROCYCLIC MCL1 INHIBITORS FOR TREATING CANCER (Fri, 27 Oct 2017)
Disclosed is a compound which is 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia-5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta- 1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid (Formula I) and enantiomers and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions of 17-chloro-5,13,14,22-tetramethyl-28-oxa-2,9-dithia- 5,6,12,13,22-pentaazaheptacyclo[27.7.1.14,7.011,15.016,21.020,24.030,35]octatriaconta- 1(37),4(38),6,11,14,16,18,20,23,29,31,33,35-tridecaene-23-carboxylic acid, and enantiomers and pharmaceutically acceptable salts thereof, and methods of treating cancer with such compounds and compositions.
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THERAPEUTIC COMPOUNDS (Fri, 27 Oct 2017)
The present disclosure relates to substituted heterocyclic derivative therapeutic compounds, compositions comprising said compounds, and the use of said compounds and compositions for epigenetic regulation by inhibition of bromodomain-mediated recognition of acetyl lysine regions of proteins, such as histones. Said compositions and methods are useful for the treatment of diseases mediated by aberrant cell signalling, such as inflammatory disorders, cancer and neoplastic disease
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HISTONE DEMETHYLASE INHIBITORS (Fri, 27 Oct 2017)
The present embodiments provide for substituted triazolylpyridine derivative compounds, and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for modulating the activity of histone demethylase enzymes. Additionally, the subject compounds and compositions are useful for the treatment of cancer or other neoplastic diseases, or maladies associated with abnormal histone demethylase activity. Accordingly, the substituted triazolylpyridine derivative compounds described herein are useful in methods and medicaments for treating cancer.
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QUINOLINE COMPOUNDS AS MODULATORS OF RAGE ACTIVITY AND USES THEREOF (Fri, 27 Oct 2017)
Quinoline compounds are disclosed that have a formula represented by the following: and wherein Cy, R1, R4a, R4b, and n are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, diabetes complications, inflammation, and neurodegeneration, obesity, cancer, ischemia/reperfusion injury, cardiovascular disease and other diseases related to RAGE activity.
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NLRP3 MODULATORS (Fri, 27 Oct 2017)
This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that modulate (e.g., agonize or partially agonize) NLRP3 and TLR7 and/or TLR8 that are useful, e.g., for treating a condition, disease or disorder in which a decrease in NLRP3 and TLR7 and/or TLR8 activities (e.g., a condition, disease or disorder associated with repressed or impaired NLRP3 and TLR7 and/or TLR8 signaling) contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions as well as other methods of using and making the same.
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NLRP3 MODULATORS (Fri, 27 Oct 2017)
This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that modulate (e.g., agonizes or partially agonizes) NLRP3 that are useful, e.g., for treating a condition, disease or disorder in which a decrease in NLRP3 activity (e.g., a condition, disease or disorder associated with repressed or impaired NLRP3 signaling) contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions as well as other methods of using and making the same.
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COMPOSITIONS AND METHODS FOR TREATING CANCER (Fri, 27 Oct 2017)
The invention provides methods for the treatment of a cancer using a galectin-3 inhibitor, such as a modified pectin (e.g., GCS-lOO). Also described are methods for assessing and/or monitoring the effects of a galectin-3 inhibitor, e.g., to adapt the dosing regimen of the inhibitor during therapy.
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FORMULATIONS OF AN LSD1 INHIBITOR (Fri, 27 Oct 2017)
The present application relates to pharmaceutical formulations and dosage forms of a lysine specific demethylase-1 (LSD1) inhibitor, or a pharmaceutically acceptable salt, solvate, or hydrate thereof, including methods of preparation thereof, which are useful in the treatment of LSD1 mediated diseases such as cancer.
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DEGRADATION OF CYCLIN-DEPENDENT KINASE 9 (CDK9) BY CONJUGATION OF CDK9 INHIBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE (Fri, 27 Oct 2017)
The present application provides bifunctional compounds of Formula (I): Targeting Ligand or a pharmaceutically acceptable salt, hydrate, solvate, prodrag, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 9 (CDK.9). The present application also relates to methods for the targeted degradation of CDK9 through the use of th e bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK9 which can be utilized in the treatment of disorders modulated by CDK9.
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DEGRADATION OF CYCLIN-DEPENDENT KINASE 4/6 (CDK4/6) BY CONJUGATION OF CDK4/6 INHIBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE (Fri, 27 Oct 2017)
The present application provides bifunctional compounds of Formula (I), or Targeting Ligand, or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 4 (CDK4) and/or cyclin-dependent kinase 6 (CDK6). The present application also relates to methods for the targeted degradation of CDK4 and/or CDK6 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK4 and/or CDK6 which can be utilized in the treatment of disorders modulated by CDK4 and/or CDK6.
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DEGRADATION OF CYCLIN-DEPENDENT KINASE 8 (CDK8) BY CONJUGATION OF CDK8 INHIBITORS WITH E3 LIGASE LIGAND AND METHODS OF USE (Fri, 27 Oct 2017)
The present application provides bifunctional compounds of Formula (la) or (lb): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 8 (CDK8). The present application also relates to methods for the targeted degradation of CDK8 through the use of the bifunctional compounds that link a ubiquitin ligase-bindmg moiety to a ligand that is capable of binding to CDK8 which can be utilized in the treatment of disorders modulated by CDK8.
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BIFUNCTIONAL MOLECULES FOR DEGRADATION OF EGFR AND METHODS OF USE (Fri, 27 Oct 2017)
The present application provides bifunctional compounds of Formula (I): Targeting Ligand which act as protein degradation inducing moieties for EGFR and/or a mutant thereof. The present application also describes methods for the targeted degradation of EGFR and/or a mutant thereof through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to EGFR and/or a mutant thereof which can be utilized in the treatment of disorders modulated by EGFR or a mutant thereof.
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Novel heterocyclic carboxamides as modulators of kinase activity (Fri, 27 Oct 2017)
The invention provides novel heterocyclic carboxamide compounds compounds according to Formula (1) their manufacture and use for the treatment of hyperproliferative diseases, such as cancer.
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Substituted quinazoline compounds and methods of use thereof (Fri, 27 Oct 2017)
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have one of the following structures (I), (II) or (III): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein R<sp>1</sp>, R<sp>2a</sp>, R<sp>2b</sp>, R<sp>2c</sp>, R<sp>3a</sp>, R<sp>3b</sp>, R<sp>4a</sp>, R<sp>4b</sp>, R<sp>5a</sp>, R<sp>5b</sp>, R<sp>6</sp>, A, B, G<sp>1</sp>, G<sp>2</sp>, L<sp>1</sp>, L<sp>2</sp>, m<sp>1</sp>, m<sp>2</sp>, n, x, y, X and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.
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TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS (Fri, 27 Oct 2017)
Tricyclic chemical modulators of FOXO transcription factor proteins are disclosed. The compounds are useful to treat cancer, age-onset proteotoxicity, stress-induced depression, inflammation, and aene. The compounds are of the following phenothiazine, dibenzoazepine and annulene and similar genera:
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Spirocyclic compounds (Fri, 27 Oct 2017)
Disclosed herein are spirocyclic compounds, together with pharmaceutical compositions and methods of ameliorating and/or treating a cancer described herein with one or more of the compounds described herein.
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PYRIDINYL AND FUSED PYRIDINYL TRIAZOLONE DERIVATIVES (Thu, 26 Oct 2017)
Disclosed are compounds of Formula 1, or pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , and R 4 are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating Type I hypersensitivity reactions, autoimmune diseases, inflammatory disorders, cancer, non-malignant proliferative disorders, and other conditions associated with BTK.
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2-MORPHOLIN-4,6-DISUBSTITUTED PYRIMIDINE DERIVATIVE, AND PREPARATION METHOD AND PHARMACEUTICAL USE THEREOF (Thu, 26 Oct 2017)
Disclosed is a 2-morpholin-4,6-disubstituted pyrimidine derivative as shown in formula (I) below, and a pharmaceutically acceptable salt, solvate, stereoisomer or prodrug thereof, and a pharmaceutical composition thereof and a use thereof, wherein the definition of each group is as shown in the description. The compound has a PI3K kinase inhibition activity, and has a relatively high inhibitive ability and a low cytotoxicity against PIK3CA mutant breast cancer cell strains T47D and MCF-7.
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Histone demethylase inhibitors (Fri, 20 Oct 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 amidopyridine or amidopyridazine 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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BISPHENOL DERIVATIVES AND THEIR USE AS ANDROGEN RECEPTOR ACTIVITY MODULATORS (Fri, 20 Oct 2017)
Compounds having a structure of Formula I or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1, R2, R3, R11a, R11b, R11c, R11d, and X, are as defined herein, are provided. Uses of such compounds for modulating androgen receptor activity, imaging diagnostics in cancer and therapeutics, and methods for treatment of subjects in need thereof, including prostate cancer are also provided.
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BROMODOMAIN INHIBITORS (Fri, 20 Oct 2017)
The present invention provides for compounds of formula (I) wherein R1, R2, R3, R4, R6, X1, and X2 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising compounds of formula (I).
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ENANTIOENRICHED VIRIDICATUMTOXIN B ANALOGS (Fri, 20 Oct 2017)
In one aspect, the present disclosure provides derivatives of viridicatumtoxin of the formula wherein the variables are as defined herein. Also provided herein are compositions and methods of treating a bacterial infection, a viral infection, or in the treatment of cancer. The present disclosure also provides methods of synthesizing enantiopure viridicatumtoxin and other anthrone compounds.
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BET PROTEIN DEGRADERS (Fri, 20 Oct 2017)
The present disclosure provides compounds represented by Formula I: and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein B, R1, R5, Q1, Q", L, X, Y, and Z are as defined as set forth in the specification. The present disclosure also provids compounds of Formula I for use to treat a condition or disorder responsive to degradation of BET bromodomains such as cancer.
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HETEROCYCLIC COMPOUNDS AS RET KINASE INHIBITORS (Fri, 20 Oct 2017)
The present invention relates to compounds of Formula I that function as inhibitors of RET (rearranged during transfection) kinase enzyme activity: wherein HET, bonds a, b, c and d, X1, X2, X3, X4, R2, and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which RET kinase activity is implicated.
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HETEROCYCLIC COMPOUNDS AS RET KINASE INHIBITORS (Fri, 20 Oct 2017)
The present invention relates to compounds of formula I that function as inhibitors of RET (rearranged during transfection) kinase enzyme activity: wherein HET, X1, X2, X3, X4, integer a and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which RET kinase activity is implicated.
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AIE NANOPARTICLE CONJUGATES AND METHODS THEREFOR (Fri, 20 Oct 2017)
Described are compositions comprising amphiphilic polymer nanoparticles, such as DSPE-PEG, encapsulating a photostable agent with aggregation-induced emission (AIE) characteristic. The photostable AIE agents are preferably small organic molecules with tetraphenylethylene moieties. The nanoparticles are synthesized by a modified nanoprecipitation method and the size of the nanoparticles is controlled by varying the loading ratio, the solvent ratio and the tatio of hydrophilic to hydrophobic length of the polymer. The nanoparticles are surface modified with a conjugatable group for covalently linking to at least one targeting moiety, such as antibodies or affibodies to IgG, EGFR and Her2. Methods for immunostaining or imaging or detecting or tracking a live cell, such as cancer cells, using the nanoparticle compositions are described.
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IMIDAZO[1,2-A]PYRIDINE COMPLEXES WITH ANTICANCER ACTIVITY (Fri, 20 Oct 2017)
This invention relates to a metal complex of an imidazo[l,2-a]pyridine ligand and/or a metal complex of an imidazo[l,2-a] pyridine ligand derivative and/or an analogue thereof, wherein said metal complexes are for use in treating cancer. Typically, the cancer is breast cancer, colorectal cancer, colon cancer, and/or leukemia.
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TG2 INHIBITOR COMPOUNDS AND USES THEREOF (Fri, 20 Oct 2017)
There are provided Tissue Transglutaminase (TG2) inhibitor compounds, and compositions and methods of use thereof for the prevention or treatment of a cancer. Compounds of Formula I, and pharmaceutically acceptable salts thereof, are provided: Formula (I).
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FOCUSED INTERFERON IMMUNOTHERAPY (Fri, 20 Oct 2017)
The present invention relates to methods of treating a proliferative disease (such as cancer) in an individual, comprising administering to the individual a non-naturally occurring fusion molecule comprising an antibody against one or more tumor-associated antigen ("TAA Ab") attached to an interferon (IFN) molecule (hereinafter "TAA Ab-IFN fusion molecule"), as monotherapy at therapeutically effective low doses, or in combination with immunotherapy, wherein the combination therapy provides increased effector cell killing. The methods of the present invention are particularly effective treating recurrent, resistant, or refractory proliferative diseases.
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SMALL MOLECULES FOR IMMUNOGENIC TREATMENT OF CANCER (Fri, 20 Oct 2017)
The present invention relates to new compounds for immunogenic treatment of cancer. The compounds can be administered as a single agent or in combination with an anticancer drug including modulators of other immune pathways, especially immune checkpoint inhibitors that target CTLA-4, PD-1, and PD-L1 proteins. The compounds can produce neoantigens through irreversible protein binding in cancer cells and generate immune response.
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NEUROTENSIN RECEPTOR BINDING CONJUGATES AND FORMULATIONS THEREOF (Fri, 20 Oct 2017)
Conjugates of an active agent attached to a neurotensin receptor-binding targeting moiety via a linker have been designed. Nanoparticles and microparticles comprising such conjugates can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or other diseases.
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METHODS AND COMPOSITIONS FOR DETECTION AND DIAGNOSIS OF BREAST CANCER (Fri, 20 Oct 2017)
The present disclosure provides methods, compositions and kits for the detection and diagnosis of breast cancer.
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METHODS FOR MONITORING AND TREATING CANCER (Fri, 20 Oct 2017)
The present invention provides therapeutic and diagnostic methods and compositions for cancer. The invention provides, inter alia, methods of treating cancer and methods of monitoring the response of a patient having a cancer to treatment with a VEGF antagonist (e.g., an anti-VEGF antibody).
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METHODS FOR MONITORING AND TREATING CANCER (Fri, 20 Oct 2017)
The present invention provides therapeutic and diagnostic methods and compositions for cancer, for example, kidney cancer. The invention provides, inter alia, methods of treating cancer and methods of monitoring the response of a patient having a cancer to treatment with an anti-cancer therapy comprising a VEGF antagonist (e.g., an anti-VEGF antibody) and a PD-L1 axis binding antagonist (e.g., an anti-PD-L1 antibody).
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DNA-PK inhibitors (Fri, 20 Oct 2017)
The present invention relates to compounds of following formula (I) useful as inhibitors of DNA-PK. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders, such as cancer.
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Antibody drug conjugates (ADC) that bind to 191P4D12 proteins (Fri, 20 Oct 2017)
Antibody drug conjugates (ADC's) that bind to 191P4D12 protein and variants thereof are described herein. 191P4D12 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, the ADC's of the invention provide a therapeutic composition for the treatment of cancer.
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NOVEL 4-(ARYL)-N-(2-ALKOXYTHIENO[3,2-B]PYRAZIN-3-YL)-PIPERAZINE-1-CARBOXAMIDE DERIVATIVE, AND ANTIPROLIFERATIVE EFFECT THEREOF (Thu, 19 Oct 2017)
The present invention relates to a novel 4-(aryl)- N- (2-alkoxythieno[3,2-b]pyrazin-3-yl)-piperazin-1-carboxamide derivative compound useful in the prevention or treatment of cancer; a preparation method thereof; and a pharmaceutical composition comprising the same. The novel 4-(aryl)- N- (2-alkoxythieno[3,2-b]pyrazin-3-yl)-piperazin-1-carboxamide derivative compound of the present invention can effectively inhibit the growth of proliferating cells, and thus can be useful in the prevention or treatment of cancer.
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BIPYRAZOLE SALT AS JAK INHIBITOR (Thu, 19 Oct 2017)
The present invention provides compounds of Formula I: or pharmaceutically acceptable salts thereof, as well as their compositions and methods of use, that inhibit the activity of Janus kinase (JAK) and are useful in the treatment of diseases related to the activity of JAK including, for example, inflammatory disorders, autoimmune disorders, cancer, and other diseases.
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PHARMACEUTICAL COMPOSITION HAVING BICYCLIC NITROGEN-CONTAINING AROMATIC HETEROCYCLIC AMIDE COMPOUND AS ACTIVE COMPONENT (Thu, 19 Oct 2017)
[Problem] Provided is a pharmaceutical composition for treating lung cancer involving mitochondrial Complex I, particularly non-small cell lung cancer. [Solution] After investigating compounds having a mitochondrial Complex I inhibitory effect, the present inventor completed the present invention by confirming that the bicyclic nitrogen-containing aromatic heterocyclic amide compounds of the present invention have a mitochondrial Complex I inhibitory effect, and that these compounds have an antitumor effect on mice carrying cancer derived from non-small cell lung cancer.
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PHARMACEUTICAL COMPOSITION HAVING BICYCLIC NITROGEN-CONTAINING AROMATIC HETROCYCLIC AMIDE COMPOUNDS AS ACTIVE INGREDIENT (Thu, 19 Oct 2017)
[Problem] To provide a pharmaceutical composition for treating various cancers in which mitochondrial complex I is involved, in particular, colon cancer, leukemia and/or malignant lymphoma. [Solution] With the invention of creating pharmaceutical compositions for treating various cancers, the inventors confirmed, on the basis of the result of intensive investigation, that pharmaceutical compositions, which contain specific bicyclic nitrogen-containing aromatic heterocyclic amide compounds having an AMPK activation effect and mitochondrial complex I is involved, in particular, colon cancer, leukemia and/or malignant lymphoma; thereby completing the present invention.
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N,N-DIMETHYL-3-[[5-(3-METHYL-2-OXO-1-TETRAHYDROPYRAN-4-YL-IMIDAZO[4,5-C]QUINOLIN-8-YL)-2-PYRIDYL]OXY]PROPAN-1-AMINE OXIDE AS ATM (ATAXIA TELANGIECTASIA MUTATED) KINASE MODULATOR FOR TREATING CANCER (Fri, 13 Oct 2017)
The specification generally relates to the compound of Formula (I), i.e. to N,N-dimethyl-3-[[5-(3-methyl-2-oxo-l-tetrahydropyran-4-yl-imidazo[4,5-c]quinolin-8-yl)-2-pyridyl]oxy]propan-l-amine oxide as ATM (ataxia telangiectasia mutated) kinase modulator for treating cancer.
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MDR-REVERSING 8-HYDROXY-QUINOLINE DERIVATIVES (Fri, 13 Oct 2017)
The present invention is related to 8-hydroxy-quinoline derivatives having multidrug-resistance reversing activity with improved selectivity and increased cytotoxicity towards multidrug-resistant cancer cells, preparation thereof and use of the same in the treatment of cancer, especially multidrug-resistant variants thereof.
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CRYSTALLINE FORMS OF LORLATINIB MALEATE (Fri, 13 Oct 2017)
This invention relates to new crystalline forms of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3- h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile(lorlatinib) maleate. The invention also relates to pharmaceutical compositions comprising lorlatinib maleate, and to methods of using lorlatinib maleate and compositions comprising it in the treatment of abnormal cell growth, such as cancer,in mammals.
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MACROCYCLIC INHIBITORS OF THE PD-1/PD-L1 AND CD80/PD-L1 PROTEIN/PROTEIN INTERACTIONS (Fri, 13 Oct 2017)
The present disclosure provides novel macrocyclic peptides which inhibit the PD-1/PD-Ll and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases. wherein: A is selected from a bond.
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METHODS OF TREATING PEDIATRIC CANCERS (Fri, 13 Oct 2017)
A method of treating a pediatric cancer in a subject in need thereof. The method includes administering to the subject a therapeutically effective amount of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, or a pharmaceutically acceptable salt thereof, or a combination thereof.
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LIQUID FORMULATIONS OF (S)-N-(5-((R)-2-(2,5-DIFLUOROPHENYL)-PYRROLIDIN-1-YL)-PYRAZOLO[1,5-A]PYRIMIDIN-3-YL)-3-HYDROXYPYRROLIDINE-1-CARBOXAMIDE (Fri, 13 Oct 2017)
A liquid formulation of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutically acceptable salts thereof, or a combination thereof and the use of the liquid formulation in the treatment of pain, cancer, inflammation, and certain infectious diseases are disclosed.
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LLS COMPOUNDS FOR TREATMENT OF CANCER (Fri, 13 Oct 2017)
The present invention provides benzamidazole compounds and methods of using the compounds as galectin-1 inhibitors.
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MDM2 PROTEIN DEGRADERS (Fri, 13 Oct 2017)
The present disclosure provides compounds represented by Formula I-A: A1− L 1−B1 I-A and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein A1, B1, and L1 are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I-A for use to treat a condition or disorder responsive to degradation of MDM2 protein such as cancer.
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SMALL MOLECULE REGULATORS OF STEROID RECEPTOR COACTIVATORS AND METHODS OF USE THEREOF (Fri, 13 Oct 2017)
Small molecule regulators of steroid receptor coactivator (SRC) family proteins are provided, as well as methods for their use in treating or preventing SRC-related diseases. The SRC-related diseases can include cancer, metabolic disorders, human immunodeficiency virus, neurodegenerative disorders, and/or inflammatory diseases. Also provided are methods for regulating SRC family proteins in a cell.
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PYRIMIDO-DIAZEPINONE KINASE SCAFFOLD COMPOUNDS AND METHODS OF TREATING PI3K-MEDIATED DISORDERS (Fri, 13 Oct 2017)
The present invention relates to use of pyrimido-diazepinone compounds that are able to modulate protein kinases such as ΡΙ3Κ-γ and PI3K-δ, which are members of the Class I Type IA and Class I Type IB family of phosphatidylinositol- 4,5-bisphosphate 3-kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.
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METHODS AND COMPOSITIONS FOR CAR T CELL THERAPY (Fri, 13 Oct 2017)
The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.
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PRODIGIOSIN ANALOGS (Fri, 13 Oct 2017)
Prodigiosin analogs which reactivate the p53 pathway are provided, as well as compositions of these compounds, and methods for reactivation of the p53 pathway using these compounds are provided. The prodigiosin analogs may be used to treat cancer in which p53 mutation plays a role, including prostate cancer, breast cancer, kidney cancer, ovarian cancer, lymphoma, leukemia, and glioblastoma, among others.
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METHODS OF TREATING PEDIATRIC CANCERS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">A method of treating a pediatric cancer in a subject in need thereof. The method includes administering to the subject a therapeutically effective amount of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, or a pharmaceutically acceptable salt thereof, or a combination thereof.</p>
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Pyrido-, Pyrazo- and Pyrimido-Pyrimidine Derivatives as mTOR Inhibitors (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">There is provided a compound of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.27mm" wi="55.88mm" file="US20170281637A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt thereof. There are also provided processes for the manufacture of a compound of Formula 1, and the use of a compound of Formula 1 as a medicament and in the treatment of cancer.</p>
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CYCLIC UREA COMPOUNDS AS TROPOMYOSIN-RELATED KINASE (TRK) iNHIBITORS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Tropomyosin-related kinase inhibitors (Trk inhibitors) are small molecule compounds useful in the treatment of disease. Trk inhibitors can be used as pharmaceutical agents and in pharmaceutical compositions. Trk inhibitors are useful in the treatment of inflammatory diseases, autoimmune disease, defects of bone metabolism and/or cancer, and are particularly useful in the treatment of osteoarthritis (OA), pain, and pain associated with OA. Trk inhibitors are also useful for inhibiting tropomyosin-related kinase A (TrkA), tropomyosin-receptor kinase B (TrkB), tropomyosin-receptor kinase C (TrkC), and/or c-FMS (the cellular receptor for colony stimulating factor-1 (CSF-1)).</p>
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USE OF THIOPYRIMIDINECARBOXAMIDE FOR TREATING CANCER (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">There is disclosed is a method of treating disease using compound having formula SX-682</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="52.32mm" wi="69.85mm" file="US20170281659A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">alone or in combination with an antineoplastic agent, microtubule affecting agents, antineoplastic agents, anti-angiogenesis agents, VEGF receptor kinase inhibitors, antibodies against the VEGF receptor, interferon, or radiation.</p>
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COMBINED CANCER THERAPY WITH IMMUNE CHECKPOINT MODULATORS AND FERMENTATION PRODUCTS BY SYMBIOTIC MICROBIOTA (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Combined therapy of cancer using an immune check point modulators (e.g., an immune checkpoint inhibitor) and a fermented product, which may be prepared using symbiotic microbiota.</p>
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PHARMACEUTICAL COMPOSITIONS AND THEIR USE FOR TREATMENT OF CANCER AND AUTOIMMUNE DISEASES (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Described herein are combination therapies for cancer (such as lymphoid malignancies) and immune diseases (such as autoimmune diseases and inflammatory diseases). The therapies comprise the combined use of inhibitors of BTK, mTOR kinase, and Bcl-2 or their signaling pathways, and immunomodulatory drugs. Also described are pharmaceutical compositions and kits comprising these inhibitors.</p>
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DERIVATIVES OF MACROCYCLIC N-ARYL-2-AMINO-4-ARYL-PYRIMIDINE POLYETHERS AS INHIBITORS OF FTL3 AND JAK (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention relates to a compound with the following formula: formula (I) or a salt and/or a pharmaceutically acceptable solvate thereof, in particular for use as a drug, in particular in the treatment of cancer, as well as to the pharmaceutical compositions that contain same and to the methods for preparing same.</p>
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ANDROGEN RECEPTOR MODULATORS AND METHODS FOR THEIR USE (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Compounds having a structure of Structure I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.64mm" wi="49.70mm" file="US20170283377A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>6</sup>, Y<sup>1 </sup>and Y<sup>2 </sup>are as defined herein, and wherein at least one of R<sup>3 </sup>or R<sup>4 </sup>is a straight-chain C<sub>1</sub>-C<sub>6 </sub>haloalkyl, are provided. Uses of such compounds for treatment of various indications, including prostate cancer, as well as methods of treatment involving such compounds are also provided.</p>
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Bruton's Tyrosine Kinase Inhibitors (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseeases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.78mm" wi="53.68mm" file="US20170283393A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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2-AMINOPYRIMIDINE COMPOUND AND PHARMACEUTICAL COMPOSITION AND USE THEREOF (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Disclosed are a 2-aminopyrimidine compound and pharmaceutical composition and use thereof. The structure of the 2-aminopyrimidine compound is as represented by formula I, in the formula, R<sub>1</sub>, R<sub>2</sub>, R<sub>3</sub>, R<sub>4</sub>, R<sub>5</sub>, X, Y, Z, W, (i) being as defined in the specification and the claims. Such compounds effectively inhibit the growth of a variety of tumor cells and have inhibitory effects on EGFR and IGF1R protease, and can be used for preparing antineoplastic drugs and overcome the tolerance induced by the existing drugs such as gefitinib, erlotinib and the like. The compound has selectivity for tumors, in particular the wild-type non-small cell lung cancer and have good pharmacokinetic characteristics.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="65.02mm" wi="66.04mm" file="US20170283398A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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THERAPEUTIC COMPOSITIONS AND RELATED METHODS OF USE (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Compositions comprising compounds that modulate pyruvate kinase M2 (PKM2) are described herein. Also described herein are methods of using the compounds that modulate PKM2 in the treatment of cancer.</p>
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BENZO-HETEROCYCLIC COMPOUNDS AND THEIR APPLICATIONS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention relates to benzoxazole derivatives having the following Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.72mm" wi="57.07mm" file="US20170283408A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The compounds of the present invention are found to possess the ability to decrease PD-L1 level, suggesting that the compounds of the invention can be used in cancer immunotherapy and treatment or prevention of sepsis or septic shock.</p>
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PYRIMIDO-DIAZEPINONE COMPOUNDS AND METHODS OF TREATING DISORDERS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention relates to novel pyrimido-diazepinone compounds, methods of modulating protein kinases, including MPS1 (TTK), ERK5 (BMK1, MAPK7), LRKK2, EphA2, polo kinase 1, 2, 3, or 4, Ack1, Ack2, Abl, DCAMKL1, ABL1, Abl mutants, DCAMKL2, ARK5, BRK, MKNK2, FGFR4, TNK1, PLK1, ULK2, PLK4, PRKD1, PRKD2, PRKD3, ROS1, RPS6KA6, TAOK1, TAOK3, TNK2, Bcr-Abl, GAK, cSrc, TPR-Met, Tie2, MET, FGFR3, Aurora, Axl, Bmx, BTK, c-kit, CHK2, Flt3, MST2, p70S6K, PDGFR, PKB, PKC, Raf, ROCK-H, Rsk1, SGK, TrkA, TrkB and TrkC, and the use of such compounds in the treatment of various diseases, disorders or conditions.</p>
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NOVEL COMPOSITIONS AND THERAPEUTIC METHODS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention is directed to novel products, variants, pharmaceutically acceptable salts and prodrugs thereof, and medical use of such compounds for the treatment and/or management of sepsis, septicemia, septic shock, ocular infection, ocular inflammation, ocular angiogenesis, rheumatoid arthritis (RA), atherosclerosis, inflammatory bowel diseases (IBD), asthma, chronic obstructive pulmonary disease, fever syndromes, cachexia, psoriasis, autoimmune diseases, cardiac diseases, retinoblastoma, cancer and/or any disorder associated with inflammation, immunomodulation and microbial infection.</p>
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Benzoquinone Derivatives For Treatment Of Cancer And Methods Of Making The Benzoquinone Derivatives (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention benzoquinone derivatives of the formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.38mm" wi="21.34mm" file="US20170283366A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and to pharmaceutically acceptable salts or solvates thereof. In formula (I) one of X or Y is hydrogen and the other one of X or Y is 3-Trifluoro-methylaniline; 3,4,5-trifluoroaniline; 4-methoxylaniline; 4-fluoroaniline; 3,3′-Dimethyl-1,1′-Biphenyl-4,4′-diamine; 2-(pyrrolidin-l-yl)ethyl)amine; 4-trifluoromethyl-benzylamine ; 4-fluorobenzyl-amine; 3,4-dimethoxybenzylamine; or 3,5-ditrifluoromethyl-benzylamine. Compounds of formula (I) have been identified as being useful in the treatment of cancer, in particular lung, breast and pancreatic cancer. The invention relates also to a method of making the benzoquinone derivatives and to methods of treatment.</p>
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COMPOSITIONS AND METHODS FOR TREATMENT OF PROSTATE CARCINOMA (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Disclosed herein are 1,4-naphthoquinone analogs, pharmaceutical compositions that include one or more of such 1,4-naphthoquinone analogs, and methods of treating and/or ameliorating diseases and/or conditions associated with a cancer, such as prostate cancer with such 1,4-naphthoquinone analogs. Also included are combination therapies wherein a 1,4-naphthoquinone analog disclosed herein, and a hormone therapy agent are provided to a subject suffering from a condition such as cancer.</p>
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INDOLE DERIVATIVES FOR THE PREVENTION AND/OR TREATMENT OF DIABETES AND ASSOCIATED METABOLIC DISORDERS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The invention relates to substituted heterocyclic indole derivatives of Formula (I), which act as activators of the AMP-activated protein kinase (AMPK) and to the use of them for the treatment and prevention of diseases or disorders regulated by AMPK. As a result, these compounds can be used for the treatment of inflammatory, autoimmune, cardiovascular, neurological diseases and cancer.</p>
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CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Chemical entities that are quinoxaline kinase inhibitors, pharmaceutical compositions and methods of treatment of cancer are described.</p>
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COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described, wherein the compounds have formula Ia:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.46mm" wi="62.48mm" file="US20170283423A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC kinase protein. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC, including rheumatoid arthritis, osteoarthritis, osteoporosis, peri-prosthetic osteolysis, systemic sclerosis, demyelinating disorders, multiple sclerosis, Charcot Marie Tooth syndrome, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, global ischemia, ulcerative colitis, Crohn's disease, immune thrombocytopenic purpura, atherosclerosis, systemic lupus erythematosis, myelopreparation for autologous transplantation, transplant rejection, glomerulonephritis, interstitial nephritis, Lupus nephritis, tubular necrosis, diabetic nephropathy, renal hypertrophy, type I diabetes, acute pain, inflammatory pain, neuropathic pain, acute myeloid leukemia, melanoma, multiple myeloma, breast cancer, prostate cancer, pancreatic cancer, lung cancer, ovarian cancer, gliomas, glioblastoma, neurofibromatosis, osteolytic bone metastases, brain metastases, gastrointestinal stromal tumors, and giant cell tumors.</p>
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MACROCYCLIC COMPOUNDS AS TRK KINASE INHIBITORS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">Compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, D, R<sup>2</sup>, R<sup>2a</sup>, R<sup>3</sup>, R<sup>3a</sup>, and Z are as defined herein, are inhibitors of Trk kinases and are useful in the treatment of pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.70mm" wi="57.07mm" file="US20170283435A1-20171005-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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TRITERPENE SAPONINS, METHODS OF SYNTHESIS AND USES THEREOF (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention relates to triterpene glycoside saponin-derived adjuvants, syntheses thereof, intermediates thereto, and uses thereof. QS-7 is a potent immuno-adjuvant that is significantly less toxic than QS-21, a related saponin that is currently the favored adjuvant in anticancer and antiviral vaccines. Tedious isolation and purification protocols have hindered the clinical development of QS-7. A novel semi-synthetic method is provided wherein a hydrolyzed prosapogenin mixture is used to synthesize QS-7, QS-21, and related analogs, greatly facilitating access to QS-7 and QS-21 analogs for preclinical and clinical evaluation.</p>
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IMMUNOMODULATORS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present disclosure provides novel macrocyclic peptides which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.</p>
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IMMUNOMODULATORS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present disclosure provides novel macrocyclic peptides which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.</p>
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CANCER VACCINE COMPOSITIONS AND METHODS OF USE THEREOF (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present application describes compositions that include an epitope of a peptide that elicits an immune response in a subject following administration. The compositions described herein include nucleic acids. The present application also describes compositions that include peptides. Also described herein are methods that include administering a composition comprising an epitope of a peptide to a subject in need thereof.</p>
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DERIVATIVES OF MACROCYCLIC N-ARYL-TRICYCLOPYRIMIDINE-2-AMINE POLYETHERS AS INHIBITORS OF FTL3 AND JAK (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present invention relates to a compound with the following formula (I): (I) or a salt and/or a pharmaceutically acceptable solvate thereof, in particular for use as a drug, in particular in the treatment of cancer, as well as to the pharmaceutical compositions that contain same and to the methods for preparing same.</p>
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BCMA BINDING MOLECULES AND METHODS OF USE THEREOF (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The invention provides antibodies, antigen binding fragments thereof, chimeric antigen receptors (CARs), and engineered T cell receptors, polynucleotides encoding the same, and in vitro cells comprising the same. The polynucleotides, polypeptides, and in vitro cells described herein can be used in an engineered CAR T cell therapy for the treatment of a patient suffering from a cancer. In one embodiment, the polynucleotides, polypeptides, and in vitro cells described herein can be used for the treatment of multiple myeloma.</p>
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METHODS FOR DETECTING OVARIAN CANCER (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present description is related to the field of ovarian cancer diagnostics. It introduces novel biomarkers that can be used to detect presence of ovarian cancer and to provide a prognosis of the disease.</p>
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MODULATION OF GLOBOSERIES GLYCOSPHINGOLIPID SYNTHESIS AND CANCER BIOMARKERS (Fri, 06 Oct 2017)
<p id="p-0001" num="0000">The present disclosure relates to methods and compositions which can modulate the globoseries glycosphingolipid synthesis. Particularly, the present disclosure is directed to glycoenzyme inhibitor compound and compositions and methods of use thereof that can modulate the synthesis of globoseries glycosphingolipid SSEA-3/SSEA-4/GloboH in the biosynthetic pathway; particularly, the glycoenzyme inhibitors target the alpha-4GalT; beta-4GalNAcT-I; or beta-3GalT-V enzymes in the globoseries synthetic pathway. Additionally, the present disclosure is also directed to vaccines, antibodies, and/or immunogenic conjugate compositions targeting the SSEA-3/SSEA-4/GLOBO H associated epitopes (natural and modified) which elicit antibodies and/or binding fragment production useful for modulating the globoseries glycosphingolipid synthesis. Moreover, the present disclosure is also directed to the method of using the compositions described herein for the treatment or detection of hyperproliferative diseases and/or conditions. Furthermore, the instant disclosure also relates to cancer stem cell biomarkers for diagnostic and therapeutic uses.</p>
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PURINE INHIBITORS OF HUMAN PHOSPHATIDYLINOSITOL 3-KINASE DELTA (Fri, 06 Oct 2017)
The instant invention provides compounds of formula (I) which are PI3K-delta inhibitors, and as such are useful for the treatment of PI3K-delta-mediated diseases such as inflamation, asthma, COPD and cancer.
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COMBINED CANCER THERAPY WITH IMMUNE CHECKPOINT MODULATORS AND FERMENTATION PRODUCTS BY SYMBIOTIC MICROBIOTA (Fri, 06 Oct 2017)
Combined therapy of cancer using an immune checkpoint modulator (e.g., an immune checkpoint inhibitor) and a fermented product prepared by symbiotic microbiota.
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N1-(3,3,3-TRIFLUORO-2-HYDROXY-2-METHYLPROPIONYL)-PIPERIDINE DERIVATIVES AS INHIBITORS OF PYRUVATE DEHYDROGENASE KINASE (Fri, 06 Oct 2017)
Compounds of the formula (I) in which X, Q, R1 and R2 have the meanings indicated in Claim 1, are inhibitors of pyruvate dehydrogenase kinase (PDHK), and can be employed, inter alia, for the treatment of diseases such as cancer.
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PURINE INHIBITORS OF HUMAN PHOSPHATIDYLINOSITOL 3-KINASE DELTA (Fri, 06 Oct 2017)
The instant invention provides compounds of formula (I) which are PI3K-delta inhibitors, and as such are useful for the treatment of PI3K-delta-mediated diseases such as inflamation, asthma, COPD and cancer.
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METHODS FOR SELECTING ANTIBODIES THAT SPECIFICALLY BIND GLYCOSYLATED IMMUNE CHECKPOINT PROTEINS (Fri, 06 Oct 2017)
Methods for producing and screening for antibodies that specifically bind to glycosylated immune checkpoint proteins (ICPs) relative to non-glycosylated ICPs are provided. Such antibodies recognize specific epitopes of glycosylated ICPs and can prevent or block the binding of a glycosylated ICP with its ligand, such as another ICP, and can inhibit the interactions between the two proteins that can lead to immunosuppression, as exemplified by the human PD-L1/PD-1 interaction. By way of specific example, human PD-L1 and PD-1 polypeptides comprising glycosylated amino acid residues within their extracellular domains are provided for generating anti-glycosylated PD-L1 or anti-glycosylated PD-1 antibodies that specifically bind PD-L1 or PD-1, respectively, and inhibit the PD-L1/PD-1 interaction. The antibodies produced and selected by the methods are especially useful as cancer therapeutics for disrupting, blocking, or neutralizing the ICP system and specific ICP interactions therein.
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CRYSTALLINE FORMS OF 2-[(2S)-1-AZABICYCLO[2.2.2]OCT-2-YL]-6-(3-METHYL-1H- PYRAZOL-4-YL)THIENO[3,2-D]PYRIMIDIN-4(3H)-ONE HEMIHYDRATE (Fri, 06 Oct 2017)
The present disclosure relates to crystalline forms of 2-[(2S)-1-azabicyclo[2.2.2]oct-2-yl]-6-(3-methyl-1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-4(3H)-one hemihydrate (Compound 1) and/or tautomers thereof, wherein Compound 1 has the structure: (I) ⋅ 0.5 H2O; processes for preparing crystalline forms of Compound 1 and/or tautomers thereof; pharmaceutical compositions comprising the crystalline forms; methods of inhibiting a cell division cycle 7 in a mammal comprising administering the crystalline forms; and methods of treating a cell division cycle 7 mediated cancer in a mammal comprising administering the crystalline forms or a pharmaceutical composition comprising the crystalline forms.
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PYRROLOTRIAZINE COMPOUNDS AS TAM INHIBITORS (Fri, 06 Oct 2017)
This application relates to compounds of Formula I, or pharmaceutically acceptable salts thereof, which are inhibitors of TAM kinases which are useful for the treatment of disorders such as cancer.
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ESTROGEN RECEPTOR MODULATORS (Fri, 06 Oct 2017)
Compounds of Formula (I) are estrogen receptor alpha modulators, where the variables in Formula (I) are described in the disclosure. Such compounds, as well as pharmaceutically acceptable salts and compositions thereof, are useful for treating diseases or conditions that are estrogen receptor alpha dependent and/or estrogen receptor alpha mediated, including conditions characterized by excessive cellular proliferation, such as breast cancer.
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NOVEL COMPOSITIONS AND THERAPEUTIC METHODS (Fri, 06 Oct 2017)
The present invention is directed to novel products, variants, pharmaceutically acceptable salts and prodrugs thereof, and medical use of such compounds for the treatment and/or management of sepsis, septicemia, septic shock, ocular infection, ocular inflammation, ocular angiogenesis, rheumatoid arthritis (RA), atherosclerosis, inflammatory bowel diseases (IBD), asthma, chronic obstructive pulmonary disease, fever syndromes, cachexia, psoriasis, autoimmune diseases, cardiac diseases, retinoblastoma, cancer and/or any disorder associated with inflammation, immunomodulation and microbial infection.
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ISOQUINOLINYL TRIAZOLONE COMPLEXES (Fri, 06 Oct 2017)
Disclosed is a complex of a compound of Formula 1, a stereoisomer thereof, or a tautomer of the compound of Formula 1 or stereoisomer thereof, and a cyclodextrin, in which the complex is an amorphous solid. This disclosure also relates to materials and methods for preparing the complex, to pharmaceutical compositions which contain the complex, and to the use of the complex to treat Type I hypersensitivity reactions, autoimmune diseases, inflammatory disorders, cancer, non-malignant proliferative disorders, and other conditions associated with BTK.
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MAGNETIC NANOPARTICLE-POLYMER COMPLEXES AND USES THEREOF (Fri, 06 Oct 2017)
The present invention relates to magnetic nanoparticles coated with block copolymers. The invention further relates to methods of increasing cellular uptake of magnetic nanoparticles and use of the coated magnetic particles to selectively kill cancer cells, treat cancer, detect cancer, and for biomedical imaging.
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BCMA BINDING MOLECULES AND METHODS OF USE THEREOF (Fri, 06 Oct 2017)
The invention provides antibodies, antigen binding fragments thereof, chimeric antigen receptors (CARs), and engineered T cell receptors, polynucleotides encoding the same, and in vitro cells comprising the same. The polynucleotides, polypeptides, and in vitro cells described herein can be used in an engineered CAR T cell therapy for the treatment of a patient suffering from a cancer. In one embodiment, the polynucleotides, polypeptides, and in vitro cells described herein can be used for the treatment of multiple myeloma.
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Syk inhibitors (Fri, 06 Oct 2017)
The present disclosure relates to compounds that are Syk inhibitors and to their use in the treatment of various disease states, including cancer and inflammatory conditions. In particular embodiments, the structure of the compounds is given by Formula I: wherein R1, R2, R3, and R4 are as described herein. The present disclosure further provides pharmaceutical compositions that include a compound of Formula I, or pharmaceutically acceptable salts or co-crystals thereof, and methods of using these compounds and compositions to treat conditions mediated by Syk. Formula I
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BICYCLIC COMPOUND (Thu, 05 Oct 2017)
Provided is a bicyclic compound having an acetyl-CoA carboxylase inhibitory action. A compound represented by the formula: wherein each symbol is as described in the DESCRIPTION, or a salt thereof has an acetyl-CoA carboxylase inhibitory action, is useful for the prophylaxis or treatment of cancer, inflammatory diseases and the like, and has superior efficacy.
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2-AMINOPYRIMIDINE COMPOUND AND PHARMACEUTICAL COMPOSITION AND USE THEREOF (Thu, 05 Oct 2017)
Disclosed are a 2-aminopyrimidine compound and pharmaceutical composition and use thereof. The structure of the 2-aminopyrimidine compound is as represented by formula I, in the formula, R 1 , R 2 , R 3 , R 4 , R 5 , X, Y, Z, W, (i) being as defined in the specification and the claims. Such compounds effectively inhibit the growth of a variety of tumor cells and have inhibitory effects on EGFR and IGF1R protease, and can be used for preparing antineoplastic drugs and overcome the tolerance induced by the existing drugs such as gefitinib, erlotinib and the like. The compound has selectivity for tumors, in particular the wild-type non-small cell lung cancer and have good pharmacokinetic characteristics.
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SUBSTITUTED BENZOAZEPINES AS TOLL-LIKE RECEPTOR MODULATORS (Thu, 05 Oct 2017)
Provided are compounds of formula (I) useful for modulation of signaling through the Toll-like receptors TLR7 and/or TLR8. The compounds have use in treating or preventing oral cancer.
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PYRROLOTRIAZINE COMPOUNDS AS TAM INHIBITORS (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">This application relates to compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.34mm" wi="61.13mm" file="US20170275290A1-20170928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable salts thereof, which are inhibitors of TAM kinases which are useful for the treatment of disorders such as cancer.</p>
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MODIFIED MITO-METFORMIN COMPOUNDS AND METHODS OF SYNTHESIS AND USE THEREOF (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The present invention provides mito-metformin compounds, pharmaceutical compositions thereof, and methods of using the mito-metformin compounds in the treatment of cancer.</p>
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METHODS FOR THE PREPARATION OF DIASTEREOMERICALLY PURE PHOSPHORAMIDATE PRODRUGS (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Methods for the preparation of diastereomerically pure phosphoramidate prodrugs of nucleosides, and intermediates useful for the preparation are provided. The nucleosides are useful for the treatment of hepatitis C and cancer.</p>
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GLYCOLIPIDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR USE IN THERAPY (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">A compound of Formula I: R1-L1-C(A)(A′)-CH<sub>2</sub>, -L2-R2 or a pharmaceutically acceptable salt thereof, for use in medicine, for example in the treatment of a disease or condition selected from the group comprising cancer, autistic spectrum disorders. Alzheimer's disease, Parkinson's disease, Huntingdon's disease, muscle wasting and viral infection, wherein: R1 is selected from a carbohydrate group or derivative thereof, hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; L1 is a linking group; L2 is a linking group; R2 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; A is selected from hydrogen and a C1-C6 alkyl group: A′ is selected from hydrogen, a C3-C6 alkyl group, and L3-R3; wherein L3 is a linking group; and R3 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; and wherein if A′ is not L3-R3, then R2 is a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group; and wherein if A′ is L3-R3, then one or both of R2 and R3 are a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group.</p>
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Malate salt of N-(4-phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclo-propane-1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide.</p>
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ASYMMETRIC BISAMINOQUINOLINES AND BISAMINOQUINOLINES WITH VARIED LINKERS AS AUTOPHAGY INHIBITORS FOR CANCER AND OTHER THERAPY (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The invention provides novel asymmetric and symmetric bisaminoquinolmes and related compounds, methods of treatment and syntheses. The novel compounds exhibit effective anticancer activity and are useful in the treatment of a variety of autophagy-related disorders.</p>
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BENZAZEPINE SULFONAMIDE COMPOUNDS (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">This invention relates to novel benzazepine sulfonamide compounds of the formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.78mm" wi="63.58mm" file="US20170275253A1-20170928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein R<sup>4 </sup>or R<sup>5 </sup>is —SO<sub>2</sub>—NR<sup>7</sup>R<sup>8 </sup>and R<sup>1 </sup>to R<sup>8 </sup>and Y are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are TLR agonists and may therefore be useful as medicaments for the treatment of diseases such as cancer, autoimmune diseases, inflammation, sepsis, allergy, asthma, graft rejection, graft-versus-host disease, immunodeficiencies, and infectious diseases.</li> </ul> </li> </ul> </p>
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Compounds for the treatment of HPV-induced carcinoma (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">A compound of Formula 1</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.03mm" wi="39.54mm" file="US20170275263A1-20170928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein,</li> <li id="ul0002-0002" num="0000">X represents an alkyl, alkylene, alkenyl, alkenylene, alkynyl or alkynylene group,</li> <li id="ul0002-0003" num="0000">optionally having at least one substituent selected from the group of —OR<sup>1 </sup>and —NR<sup>1</sup>R<sup>2</sup>, or</li> <li id="ul0002-0004" num="0000">Y represents —OTBS, —OR<sup>1</sup>, —NR<sup>1</sup>R<sup>2</sup>;</li> <li id="ul0002-0005" num="0000">Z represents —OR<sup>3 </sup>or ═O; and</li> <li id="ul0002-0006" num="0000">R<sup>1</sup>, R<sup>2 </sup>and R<sup>3 </sup>each independently stand for H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterocyclyl,</li> <li id="ul0002-0007" num="0000">optionally in the form of enantiomers racemic mixtures, or pharmaceutically acceptable salts thereof, for use as a medicament, in particular for use in anti-viral cancer treatment in mammals and for use in treatment of benign or neoplastic genital Human Papilloma Virus associated diseases and for use in treatment of non-genital warts.</li> </ul> </li> </ul> </p>
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HISTONE DEMETHYLASE INHIBITORS (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Provided herein are substituted pyrazolylpyridine, pyrazolylpyridazine, and pyrazolylpyrimidine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.</p>
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N-PYRIDINYL ACETAMIDE DERIVATIVES AS INHIBITORS OF THE WNT SIGNALING PATHWAY (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Disclosed are compounds useful as inhibitors of the Wnt signalling pathway. Specifically, inhibitors of Porcupine (Porcn) are contemplated by the invention. In addition, the invention contemplates processes to prepare the compounds and uses of the compounds. The compounds of the invention may therefore be used in treating conditions mediated by the Wnt signalling pathway, for example, in treating cancer, sarcoma, melanoma, skin cancer, haematological tumors, lymphoma, carcinoma, and leukemia; or enhancing the effectiveness of an anti-cancer treatment.</p>
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SUBSTITUTED CYCLOALKENOPYRAZOLES AS BUB1 INHIBITORS FOR THE TREATMENT OF CANCER (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Compounds of formula (I), processes for their production and their use as Bub1 kinase inhibitors for the treatment of hyperproliferative diseases and/or disorders responsive to induction of cell death.</p>
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NOVEL CAPSAZEPINE ANALOGS FOR THE TREATMENT OF CANCER AND OTHER PROLIFERATIVE DISEASES (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The present disclosure relates generally to derivatives of capsazepine and methods of use thereof In some aspects, the present disclosure relates to using capsazepine derivatives to treat cancer or other hyperproliferative diseases. In some aspects of the present disclosure, the disclosure provides capsazepine derivatives which may be useful in the treatment of cancer. Such cancers that the compounds may be used to treating include but are not limited to breast, cervical, oral, head, neck, or prostate cancer. In some aspects, the compounds may be useful in treating a tumor by direct injection of the compound into the tumor, particularly an oral tumor. In other aspects, the compounds are administered systemically. The compounds of the present disclosure may also be used to treat the pain associated with a tumor for which it is being administered.</p>
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TREATMENT OF CANCER USING TLR9 AGONIST WITH CHECKPOINT INHIBITORS (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The invention provides methods of inducing an immune response to cancer comprising co-administering to a cancer patient one or more TLR9 agonists and one or more checkpoint inhibitors. Preferably, the one or more TLR9 agonists are administered to the patient via intratumoral (i.t.) administration.</p>
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GENE DELIVERY SYSTEM USING POLYMER NETWORK (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Provided is a gene delivery including a polymer network formed by binding phenylboronic acid, sugar, and a low-molecular weight branched polymer. The gene delivery may be stably maintained in vivo and efficiently deliver a gene specifically to cancer cells, such that the gene delivery system may be usefully used as a gene delivery system for chemotherapy.</p>
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ANTI-TUMOR COMPOUND AND THE MEDICAL USE THEREOF (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The invention disclose a compound of formula (I), wherein, R<sub>1 </sub>is selected from —H or C1-C6 hydrocarbon group, —NH<sub>2</sub>, —OH, —O(CH<sub>2</sub>)<sub>n</sub>CH<sub>3 </sub>(n=0, 1 or 2), —N(CH<sub>3</sub>)<sub>2</sub>, or —CH<sub>2</sub>N(CH<sub>3</sub>)<sub>2</sub>, R<sub>2 </sub>is selected from an amino acid</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="14.99mm" wi="17.44mm" file="US20170273933A1-20170928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or an hydroxy acid</p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="13.04mm" wi="17.44mm" file="US20170273933A1-20170928-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005" num="0000">or —OH (R<sub>1</sub>, R<sub>2 </sub>are not —CH<sub>3 </sub>and —OH at the same time), wherein X, Y are</p> <p id="p-0006" num="0000"><chemistry id="CHEM-US-00003" num="00003"> <img id="EMI-C00003" he="205.06mm" wi="43.18mm" file="US20170273933A1-20170928-C00003.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0007" num="0000">—H, —CH<sub>3</sub>, —CH<sub>2</sub>OH, —CH(OH)CH<sub>3</sub>, —CH<sub>2</sub>SH, —CH(CH<sub>3</sub>)<sub>2</sub>, —CH<sub>2</sub>CH(CH<sub>3</sub>)<sub>2</sub>, —CH(CH<sub>3</sub>)CH<sub>2</sub>CH<sub>3</sub>, —CH<sub>2</sub>CH<sub>2</sub>SCH<sub>3</sub>, —CH<sub>2</sub>COOH, —CH<sub>2</sub>CONH<sub>2</sub>, —CH<sub>2</sub>CH<sub>2</sub>COOH, —CH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>NH<sub>2</sub>, or —CH<sub>2</sub>CH<sub>2</sub>CONH<sub>2</sub>, R<sub>3</sub>-R<sub>5 </sub>are H or C1-C6 hydrocarbon group. The compound has a low toxicity, can significantly inhibit the migration and invasion of tumor cells in vitro, and can inhibit tumor metastasis in vivo in mice at low concentration, while showing notable sensitizing effect on cytotoxic anti-tumor drugs such as Paclitaxel etc.</p> <p id="p-0008" num="0000"><chemistry id="CHEM-US-00004" num="00004"> <img id="EMI-C00004" he="27.86mm" wi="53.42mm" file="US20170273933A1-20170928-C00004.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Taxane Analogs for the Treatment of Brain Cancer (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Provided herein are compounds and methods for the treatment of brain cancer in a mammal, wherein the method comprises the administration to the mammal a compound that stabilizes tubulin dimers or microtubles at G2-M interface during mitosis but is not a substrate for MDR protein. In particular, the present application relates to the use of an orally effective abeo-taxane, alone or in combination with temozolomide or bevacizumab, for the treatment of brain cancer.</p>
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PULSE DOSING REGIMEN AND METHODS OF TREATMENT (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">A novel dosing regimen for erlotinib or a pharmaceutically acceptable salt thereof is described herein. The dosing regimen demonstrates impressive control of central nervous system disease, which is better than that reported with standard dose erlotinib. The use of the novel dosing regimen for treating patients in need thereof, including for controlling formation of metastatic brain, leptomeninges, or CNS lesions in a patient with non-small cell lung cancer (NSCLC) that harbors epidermal growth factor receptor (EGFR) mutation with or without pre-existing brain metastases, is also described herein.</p>
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A METHOD AND COMPOSITION FOR TREATING BREAST CANCER (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The invention disclosed herein relates to the use of an extract of <i>Dodonaea viscosa </i>in breast cancer therapy, either alone or in combination with other breast cancer therapies.</p>
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Pharmaceutical compounds and use of same in cancer and tauopathies (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">Disclosed are compounds of formula (l)-(V): where the substituents are as provided herein. Further disclosed are methods of inhibiting tau aggregation, treating or ameliorating a tauopathy or cancer by administration of such a compound. Tau is a microtubule-binding protein that accumulates in a number of neurodegenerative disorders, including frontotemporal dementia and Alzheimer's disease (AD). The presence of abnormal tau correlates with neuron loss and memory deficits in patients with AD and other neurodegenerative disorders that involve tau accumulation.</p>
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Drug delivery of temozolomide for systemic based treatment of cancer (Fri, 29 Sep 2017)
<p id="p-0001" num="0000">The present invention relates to methods of drug delivery for the treatment of a condition or disease, such as cancer. In one embodiment, the invention provides a method of preparing a multifunctional nanoconjugate of temozolomide (TMZ) by conjugating TMZ in its hydrazide form to a polymalic acid platform. In another embodiment, the polymalic acid platform is conjugated to a monoclonal antibody to transferrin receptor, a trileucine (LLL) moiety, and/or a polyethylene glycol (PEG) moiety. The present invention relates to methods of drug delivery for the treatment of a condition or disease, such as cancer. In one embodiment, the invention provides a method of preparing a multifunctional nanoconjugate of temozolomide (TMZ) by conjugating TMZ in its hydrazide form to a polymalic acid platform. In another embodiment, the polymalic acid platform is conjugated to a monoclonal antibody to transferrin receptor, a trileucine (LLL) moiety, and/or a polyethylene glycol (PEG) moiety.</p>
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CINNOLIN-4-AMINE COMPOUNDS AND THEIR USE IN TREATING CANCER (Fri, 29 Sep 2017)
This specification generally relates to compounds of Formula (I). And pharmaceutically acceptable salts thereof, where R1, R2 and R3 have any of the meanings defined herein. The specification also relates to the use of such compounds and salts thereof to treat or prevent ATM kinase mediated disease, including cancer. The specification further relates to crystalline forms of compounds of Formula (I) and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds and salts thereof; kits comprising such compounds and salts thereof; methods of manufacture of such compounds and salts thereof; intermediates useful in the manufacture of such compounds and salts thereof; and to methods of treating ATM kinase mediated disease, including cancer, using compounds of Formula (I) and salts thereof alone or in combination with other therapies.
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QUINOLINE-3-CARBOXAMIDE COMPOUNDS AND THEIR USE IN TREATING CANCER (Fri, 29 Sep 2017)
This specification generally relates to compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, where R1, R2, R3, R4 and R5 have any of the meanings defined herein. The specification also relates to the use of such compounds and salts thereof to treat or prevent ATM kinase mediated disease, including cancer. The specification further relates to crystalline forms of compounds of Formula (I) and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds and salts thereof; kits comprising such compounds and salts thereof; methods of manufacture of such compounds and salts thereof; intermediates useful in the manufacture of such compounds and salts thereof; and to methods of treating ATM kinase mediated disease, including cancer, using such compounds and salts thereof alone or in combination with other therapies.
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1H-BENZO[DE]ISOQUINOLINE-1,3(2H)-DIONES (Fri, 29 Sep 2017)
The present invention covers 1 /-/-benzo[c/e]isoquinoline-1,3(2/-/)-dione compounds of general formula (I) compounds of general formula (I) : in which R1, R2, R3, R4 and R5 are as defined according to claim 1 and methods of preparing said compounds, as well as their use for the treament of cancer.
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USE OF NUCLEOSOME-TRANSCRIPTION FACTOR COMPLEXES FOR CANCER DETECTION (Fri, 29 Sep 2017)
The invention relates to the use of tissue specific transcription factor-nucleosome adducts or transcription cofactor-nucleosome adducts as biomarkers in a biological fluid for the detection or diagnosis of a cancer in a subject. The invention further relates to using said tissue specific transcription factor or cofactor adducts to identify the site of development of a cancer in a subject.
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PULSE DOSING REGIMEN AND METHODS FOR TREATMENT (Fri, 29 Sep 2017)
A novel dosing regimen for erlotinib or a pharmaceutically acceptable salt thereof is described herein. The dosing regimen demonstrates impressive control of central nervous system disease, which is better than that reported with standard dose erlotinib. The use of the novel dosing regimen for treating patients in need thereof, including for controlling formation of metastatic brain, leptomeninges, or CNS lesions in a patient with non-small cell lung cancer (NSCLC) that harbors epidermal growth factor receptor (EGFR) mutation with or without pre-existing brain metastases, is also described herein.
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THERAPEUTIC COMPOSITIONS AND USES THEREOF (Fri, 29 Sep 2017)
This invention provides pharmaceutical and cosmeceutical compositions, including anti-epithelial cancer compositions, containing glyceride compounds, and compositions comprising one or more of these compounds. Methods of preparing and using such compositions, in particular in the treatment or prevention of epithelial cancers, such as skin cancers, gastrointestinal cancers, and skin disorders, are also provided.
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1,4,5-SUBSTITUTED 1,2,3-TRIAZOLE ANALOGUES AS ANTAGONISTS OF THE PREGNANE X RECEPTOR (Fri, 29 Sep 2017)
In an aspect, the invention relates to 1,4,5 -substituted 1,2,3-triazole and 1,2,4,5- substituted imidazoles, which are modulators the pregnane X receptor ("PXR"); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of modulating an adverse drug reaction in a mammal using the compounds and pharmaceutical compositions; methods of treatment of a disorder of uncontrolled cellular proliferation, such as a cancer, using the compounds and pharmaceutical compositions; methods of modulating pregnane X receptor activity in a mammal using the compounds and pharmaceutical compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
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ELECTRON WITHDRAWING GROUP SUBSTITUTED AND MACROCYCLIC PGJ3 ANALOGS AND METHODS OF TREATMENT THEREOF (Fri, 29 Sep 2017)
In some aspects, the present disclosure provides compounds of the formula: wherein the variables are as defined herein. In some embodiments, the present disclosure provides macrocylic compounds and oligomers thereof of formula I. As described herein, these compounds may be used to treat cancer or other hyperproliferative diseases.
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USE OF BENZOFURAN LIGNANS TO INDUCE IL-25 EXPRESSION AND SUPPRESS MAMMARY TUMOR METASTASIS (Fri, 29 Sep 2017)
A method for suppressing tumor metastasis, in which an effective amount of a compound of formula (I) is administered to a subject in need thereof. Also disclosed is a method of treating cancer, in which an effective amount of a chemotherapy agent and an effective amount of a compound of formula (I) is administered to a subject in need thereof. Further disclosed are pharmaceutical compositions for suppressing tumor metastasis and for treating cancer, each of the compositions containing a compound of formula (I).
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SMALL MOLECULE INHIBITOR OF THE NUCLEAR TRANSLOCATION OF ANDROGEN RECEPTOR FOR THE TREATMENT OF CASTRATION-RESISTANT PROSTATE CANCER (Fri, 29 Sep 2017)
A compound, or a stereoisomer, pharmaceutically acceptable salt, or ester thereof, according to formula (III) or according to Table A, a pharmaceutical composition comprising said compound and at least one pharmaceutically acceptable additive, and a method for treating prostate cancer in a subject, comprising administering to the subject a therapeutically effective amount of said compound.
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Diarylhydantoin compounds (Fri, 29 Sep 2017)
The present invention relates to diarylhydantoin compounds, including diarylthiohydantoins, and methods for synthesizing them and using them in the treatment of hormone refractory prostate cancer.
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Biomarkers and methods of treating PD-1 and PD-L1 related conditions (Fri, 29 Sep 2017)
Provided herein are biomarkers for the treatment of pathological conditions, such as cancer, and method of using PD-I/PD-LI pathway antagonists. In particular, provided are biomarkers for patient selection and prognosis in cancer, as well as methods of therapeutic treatment, articles of manufacture and methods for making them, diagnostic kits, methods of detection and methods of advertising related thereto.
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PYRAZOL-3-ONES THAT ACTIVATE PRO-APOPTOTIC BAX (Fri, 29 Sep 2017)
This application features pyrazol-3-one compounds that activate pro-apoptotic BAX. Also featured are methods of using such compounds, e.g., for the treatment or prevention of diseases, disorders, and conditions associated with deregulated apoptosis of cells (e.g., insufficient apoptosis of diseased or damaged cells or essentially the absence of apoptosis of diseased or damaged cells). See Fig. 1A.
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Method of treating cancer and bone cancer pain (Fri, 29 Sep 2017)
This invention is directed to the treatment of cancer, particularly lung cancer, breast cancer, melanoma, renal cell carcinoma, thyroid cancer that has metastasized to the bone. The invention is also directed to a method for treating bone cancer pain in an individual in need of such treatment comprising administering to the individual an effective amount of a compound of Formula I.
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BIGUANIDE COMPOUND AND USE THEREOF (Thu, 28 Sep 2017)
The present invention relates to a guanidine compound and a use thereof, and more specifically, to a guanidine derivative showing excellent effects of inhibiting cancer cell proliferation, cancer metastasis, and cancer recurrence; a preparation method thereof; and a pharmaceutical composition containing the same as an active ingredient. Compared to existing drugs, the guanidine derivative according to the present invention shows excellent effects of inhibiting cancer cell proliferation, cancer metastasis, and cancer recurrence even with small doses, and may thus be effectively used in preventing or treating various cancers such as uterine cancer, breast cancer, stomach cancer, brain cancer, rectal cancer, colorectal cancer, lung cancer, skin cancer, blood cancer, liver cancer, etc., inhibiting cancer cell proliferation and cancer metastasis.
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PSMA-BINDING AGENTS AND USES THEREOF (Thu, 28 Sep 2017)
Prostate-specific membrane antigen (PSMA) binding compounds having radioisotope substituents are described, as well as chemical precursors thereof. Compounds include pyridine containing compounds, compounds having phenylhydrazine structures, and acylated lysine compounds. The compounds allow ready incorporation of radionuclides for single photon emission computed tomography (SPECT) and positron emission tomography (PET) for imaging, for example, prostate cancer cells and angiogenesis.
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LIPIDATED IMMUNE RESPONSE MODIFIER COMPOUND AND ITS MEDICAL USE (Thu, 28 Sep 2017)
The compound N-(4-{[4-amino-2-butyl-1 H -imidazo[4,5- c ]quinolin-1-yl]oxy}butyl)octadecanamide is a useful drug compound for enhancing immune response and can be used, for example, as a vaccine adjuvant and a cancer treatment.
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NOVEL PEPTIDE COMPOUND, PRODUCTION METHOD THEREFOR, AND USE THEREOF (Thu, 28 Sep 2017)
A novel peptide compound, a production method thereof, and a use thereof are provided. The compound has an anticancer activity and, thus the compound can be used for the preventing or treating cancer.
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FLUORESCENT SILICA-BASED NANOPARTICLES (Thu, 28 Sep 2017)
The present invention provides a fluorescent silica-based nanoparticle that allows for precise detection, characterization, monitoring and treatment of a disease such as cancer. The nanoparticle has a range of diameters including between about 0.1 nm and about 100 nm, between about 0.5 nm and about 50 nm, between about 1 nm and about 25 nm, between about 1 nm and about 15 nm, or between about 1 nm and about 8 nm. The nanoparticle has a fluorescent compound positioned within the nanoparticle, and has greater brightness and fluorescent quantum yield than the free fluorescent compound. The nanoparticle also exhibits high biostability and biocompatibility. To facilitate efficient urinary excretion of the nanoparticle, it may be coated with an organic polymer, such as poly(ethylene glycol) (PEG). The small size of the nanoparticle, the silica base and the organic polymer coating minimizes the toxicity of the nanoparticle when administered in vivo. In order to target a specific cell type, the nanoparticle may further be conjugated to a ligand, which is capable of binding to a cellular component associated with the specific cell type, such as a tumor marker. In one embodiment, a therapeutic agent may be attached to the nanoparticle. To permit the nanoparticle to be detectable by not only optical fluorescence imaging, but also other imaging techniques, such as positron emission tomography (PET), single photon emission computed tomography (SPECT), computerized tomography (CT), bioluminescence imaging, and magnetic resonance imaging (MRI), radionuclides/radiometals or paramagnetic ions may be conjugated to the nanoparticle.
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MNK inhibitors and methods related thereto (Fri, 22 Sep 2017)
<p id="p-0001" num="0000">The present invention relates to compounds according to Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="65.11mm" file="US09814718-20171114-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4a</sup>, R<sup>4b</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>7</sup>, R<sup>8</sup>, W<sup>1</sup>, W<sup>2</sup>, Y and n are as defined herein. Also described are pharmaceutically acceptable compositions of Formula I compounds as well as methods for utilizing the compounds of Formula I and the pharmaceutically acceptable compositions of Formula I compounds as inhibitors of Mnk as well as therapeutics for the treatment of diseases such as cancer. </p>
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Anticancer miliusane lactams (Fri, 22 Sep 2017)
<p id="p-0001" num="0000">The present invention is in the field of pharmaceuticals and chemical industries. In particular, the present invention relates to new anticancer miliusane lactam compounds. The present invention also includes its preparation and application method for treating cancer.</p>
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NOVEL SELENAZOLIDINE AND THIAZOLIDINE COMPOUNDS FOR TREATING CANCER AND OTHER DISEASES (Fri, 22 Sep 2017)
The present invention includes compounds useful in preventing or treating cancer in a subject in need thereof. The present invention also includes methods of preventing or treating cancer in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention.
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INHIBITORS FOR SOLUBLE EPOXIDE HYDROLASE (SEH) AND FATTY ACID AMIDE HYDROLASE (FAAH) (Fri, 22 Sep 2017)
The present invention provides compounds that are dual inhibitors of soluble epoxide hydrolase and fatty acid amide hydrolase. The present invention also provides methods of using the compounds to inhibit soluble epoxide hydrolase and fatty acid amide hydrolase, and to treat cancer.
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KNOTTIN-DRUG CONJUGATES AND METHODS OF USING THE SAME (Fri, 22 Sep 2017)
Provided are knottin-drug conjugates. The conjugates include a knottin peptide that includes an engineered loop that binds to a target on a cancer cell surface, and a drug (e.g., a nucleoside drug) conjugated to the knottin peptide through a linker. Also provided are pharmaceutical compositions and kits that include the knottin-drug conjugates, as well as methods of using the knottin-drug conjugates, e.g., for therapeutic purposes.
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AZA-A-RING INDENOISOQUINOLINE TOPOISOMERASE I POISONS (Fri, 22 Sep 2017)
The invention described herein pertains to four series of aza-A-ring indenoisoquinolines, which are inhibitors of topoisomerase IB (Top1), and the processes for preparing said aza-A-ring indenoisoquinolines. Also described are methods for treating cancer in mammals using the described aza-A-ring indenoisoquinoline compounds or pharmaceutical formulations thereof.
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HISTONE DEMETHYLASE INHIBITORS (Fri, 22 Sep 2017)
The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted pyrido[3,4-d] pyrimidin-4-one derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, melanoma, and the like.
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NANOPARTICLE TO TARGET CANCER (Fri, 22 Sep 2017)
A construct, or a pharmaceutically acceptable salt thereof, comprising: (a) a polyethylene glycol-block-poly(L-lysine) polymer moiety, wherein the polyethylene glycol is thiol-functionalized; (b) a cholecystokinin-B (CCK-B) receptor ligand coupled to the polyethylene glycol of the polymer moiety; and (c) a siRNA complexed with the poly(L-lysine) of the polymer moiety, wherein the construct is neutralized.
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HISTONE DEMETHYLASE INHIBITORS (Fri, 22 Sep 2017)
The present invention relates generally to compositions and methods for treating cancer and neoplastic diseases. Provided herein are substituted imidazole-pyridine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of histone demethylase enzymes. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as pancreatic cancer, prostate cancer, breast cancer, bladder cancer, lung cancer, gastric cancer, leukemia and/or melanoma and the like.
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EPHRIN RECEPTOR A2 (EPHA2)-TARGETED DOCETAXEL-GENERATING NANO-LIPOSOME COMPOSITIONS (Fri, 22 Sep 2017)
EphA2-targeted immunoliposomes for delivering docetaxel are useful in the treatment of certain types of cancer. The immunoliposomes can include an EphA2 targeting moiety (e.g., a scFv) and encapsulate a docetaxel prodrug in a stable salt form within a liposome having an average size of about 100 nm. Novel docetaxel prodrugs suitable for loading into nanoliposomes (including immunoliposomes) are provided, along with novel and other useful EphA2 targeting moieties for preparation of EphA2-targeted doxorubicin-generating immunoliposome therapies. Pharmaceutical compositions can be prepared that include nanoliposomes encapsulating one or more docetaxel prodrugs, and/or immunoliposomes or nanoparticles comprising an EphA2 binding moiety and encapsulating one or more docetaxel prodrugs. The pharmaceutical compositions are useful for administration to a patient for the treatment of cancer.
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TREATING EPHRIN RECEPTOR A2 (EPHA2) POSITIVE CANCER WITH TARGETED DOCETAXEL-GENERATING NANO-LIPOSOME COMPOSITIONS (Fri, 22 Sep 2017)
EphA2 targeted doxorubicin generating nano-liposomes are useful in the treatment of cancer overexpressing EphA2, alone or in combination with chemotherapeutic agents such as gemcitabine or carboplatin.
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ANTIBODY MIMIC CONJUGATES AND PARTICLES (Fri, 22 Sep 2017)
Particles, including nanoparticles and microparticles, and pharmaceutical formulations thereof, comprising conjugates of an active agent such as a therapeutic, prophylactic, or diagnostic agent attached to a targeting moiety via a linker have been designed which can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or infectious diseases.
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SMALL MOLECULES AGAINST CEREBLON TO ENHANCE EFFECTOR T CELL FUNCTION (Fri, 22 Sep 2017)
Disclosed are small molecules against cereblon to enhance effector T cell function. Methodos of making thes molecules and methods of using them to treat various disease states are also disclosed.
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CARBONIC ANHYDRASE IX INHIBITOR CONJUGATES AND USES THEREOF (Fri, 22 Sep 2017)
The present disclosure relates to compositions and methods of carbonic anhydrase IX inhibitors. The present disclosure also relates to targeting conjugates of carbonic anhydrase IX inhibitors as therapeutics and imaging agents. The present disclosure also relates to the use of targeting conjugates of carbonic anhydrase IX inhibitors in imaging methods and cancer therapy.
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COMBINATIONS OF COPANLISIB (Fri, 22 Sep 2017)
The present invention relates to * combinations of : component A : one or more 2,3-dihydroimidazo[l,2-c]quinazoline compounds of general formula (Al) or (A2) as defined herein, or a physiologically acceptable salt, solvate, hydrate or stereoisomer thereof; component B : one or more IRAK4-inhibiting compounds of general formula (I) as defined herein, or a physiologically acceptable salt, solvate, hydrate or stereoisomer thereof; in which optionally some or all of the components are in the form of a pharmaceutical formulation which is ready for use to be administered simultaneously, concurrently, separately or sequentially. dependently of one another by the oral, intravenous, topical, local installations, intraperitoneal or nasal route; * use of such combinations for the preparation of a medicament for the treatment or prophylaxis of a cancer; and * a kit comprising such a combination.
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ANTI-MICA ANTIBODIES (Fri, 22 Sep 2017)
The present invention provides antigen-binding proteins capable of binding to human MICA polypeptides. The antigen-binding proteins have increased activity in the treatment of disorders characterized by MICA-expressing cells, particularly cancer.
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ANTI-CD39 ANTIBODIES (Fri, 22 Sep 2017)
The present invention relates to antigen-binding compounds that inhibit CD39. The invention also relates to cells producing such compounds; methods of making such compounds, and antibodies, fragments, variants, and derivatives thereof; pharmaceutical compositions comprising the same; methods of using the compounds to diagnose, treat or prevent diseases, e.g. cancer.
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ENHANCERS OF NOTCH SIGNALING AND THEIR USE IN THE TREATMENT OF CANCERS AND MALIGNANCIES MEDICABLE BY UPREGULATION OF NOTCH (Fri, 22 Sep 2017)
The present invention relates to the use for enhancing Notch signaling in an individual, of a compound showing the general formula (I) and/or a pharmaceutically acceptable salt or ester thereof, for the treatment of a disease selected from the group of dermatological disorders including atopic dermatitis, psoriasis, immune related disorders, cancer, squamous cell carcinoma, cutaneous and lung squamous cell carcinoma, head and neck cancer, non-melanoma skin cancer, basal cell carcinoma and actinic keratosis, neuroendocrine tumors, neuroendocrine small cell carcinoma and carcinoid tumors, thyroid carcinomas, muscular disorders muscular dystrophy and impaired regeneration capacity after injury; use in immunotherapy for cancer.
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4,6 DIHYDROPYRROLO [3,4-C] PYRAZOLE-5 (1H)-CARBONITRILE DERIVATES FOR TRATING CANCER (Fri, 22 Sep 2017)
The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs) and/ or desumoylating enzymes. In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 7 or ubiquitin specific peptidase 7 (USP7). The invention further relates to the use of DUB or desumoylating inhibitors in the treatment of cancer. Described herein are compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1a, R1b, R1c and R1d each independently represent hydrogen, optionally substituted C1-C6 alkyl or R1a and R1b together form an optionally substituted C3-C6 cycloalkyl ring, or R1c and R1d together form an optionally substituted C3-C6 cycloalkyl ring; A is a 5 membered nitrogen-containing aromatic ring and is substituted with at least one optionally substituted 5 to 10 membered monocyclic or bicyclic heteroaryl or aryl ring attached through an optional linker.
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2-CYANOISOINDOLINE DERIVATIVES FOR TREATING CANCER (Fri, 22 Sep 2017)
The invention relates to novel compounds of formula I which are inhibitors of deubiquitylating enzymes (DUBs) and/or desumoylating enzymes. In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 7 or ubiquitin specific peptidase 7 (USP7). The invention further relates to methods for the preparation of these compounds and to their use in the treatment of cancer.
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FUSION PROTEINS TARGETING TUMOUR ASSOCIATED MACROPHAGES FOR TREATING CANCER (Fri, 22 Sep 2017)
The present invention relates to cancer immunotherapy. In particular, provided herein are fusion proteins for targeting tumor associated macrophages with immunostimulatory agents.
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OLIGOLACTIC ACID CONJUGATES AND MICELLES WITH ENHANCED ANTICANCER EFFICACY (Fri, 22 Sep 2017)
The present technology relates generally to oligolactic acid conjugates of paclitaxel, rapamycin, selumetinib, and other anticancer agents, micelle compositions containing such conjugates and methods of preparing and using such compositions to treat various cancers. Specifically, there are provided oligolactic acid conjugates wherein the oligolactic acid comprises 2 to 24 lactic acid subunits and is attached through an ester linkage to the oxygen of the 7-hydroxyl of the paclitaxel or paclitaxel derivative, the 40-hydroxyl of the rapamycin or rapamycin derivative, and the 2'-hydroxyl of the selumetinib or selumetinib derivative. Compositions comprising water and a micelle comprising a polylactic acid-containing polymer and the oligolactic acid conjugate may be readily prepared. Methods of inhibiting or killing cancer cells and treating paclitaxel, rapamycin, and/or selumetinib cancers are also provided.
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3-(3H-imidazo[4,5-B]pyridin-2-yl)-1H-pyrazolo[3,4-C]pyridine and therapeutic uses thereof (Fri, 15 Sep 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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2-(1H-indazol-3-yl)-1H-imidazo[4,5-C]pyridine and therapeutic uses thereof (Fri, 15 Sep 2017)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, 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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4BETA-AMIDOTRIAZOLE LINKED PODOPHYLLOTOXIN DERIVATIVES AS POTENTIAL ANTICANCER AGENTS (Fri, 15 Sep 2017)
The present invention relates to a compound of general formula (A). The invention provides asynthesis of new 4β-amidotriazole linked podophyllotoxin derivatives of general formulae 8a-z to 9a-z useful as potential anticancer agents against human cancer cell lines and process for the preparation thereof. Wherein n = 0,1 and R1-R5 = [H, CI, F, CH3, OCH3, 3,4(-OCH2O-), CF3, OCF3, m-OC6H5, OH]
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TOTAL CELLULAR IRON AS A MARKER OF CANCER STEM CELLS AND USES THEREOF (Fri, 15 Sep 2017)
The present invention relates to a novel use of total cellular iron, preferably under the form of ferrous iron (Fe2+), as a marker of cancer stem cells (CSCs). The invention also relates to methods using said iron marker, in particular for metastatic cancer diagnosis or treatment, for screening for compounds of interest, as well as for killing CSCs.
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3-OXA-8-AZABICYCLO[3.2.1]OCTANE DERIVATIVES AND THIER USE IN THE TREATMENT OF CANCER AND HEMOGLOBINOPATHIES (Fri, 15 Sep 2017)
A compound of formula Ia, Ib, Ic or Id: wherein: n is 1 or 2;R N is H or Me; R1 is optionally one or more halo or methyl groups;R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H;(iii) Me; and (iv) CH2 OH; R 2c and R 2d (if present) are independently selected from the group consisting of: (i) F; (ii) H;(iii) Me; and(iv) CH 2 OH;R 3a and R 3b are independently selected from H and Me; R 4a is selected from OH,-NH 2, -C(=O)NH 2, and -CH 2 OH; R 4b is either H or Me; R5 is either H or Me; m is 1 or 2; q is 0 or 1;R 11a, R 11b, R 11c and R 11d are independently selected from H, halo, C1-4 alkyl, C 1-4 fluoroalkyl, C 3-4 cycloalkyl, C 1-4 alkyloxy, NH-C 1-4 alkyl and cyano; R 12a and R 12b are independently selected from the group consisting of: (i) F; (ii) H;(iii) Me; and (iv) CH 2 OH; R 12c and R 12d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH 2 OH;R 12e is H or Me; R 13a and R 13b are independently selected from H and Me; R 14 is either H or Me; R 16a and R 16b are independently selected from H and Me; R 6 is selected from H, OMe, and OEt.
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BENZOPIPERIDINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF CANCER AND HEMOGLOBINOPATHIES (Fri, 15 Sep 2017)
A compound of formula I: (I) wherein: n is 1 or 2; p is 0 or 1; R1a, R1b, R1c and R1d are independently selected from H, halo, C1-4 alkyl, C1-4 fluoroalkyl, C3-4 cycloalkyl, C1-4 alkyloxy, NH-C1-4 alkyl and cyano; R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2c and R2d are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2e is H or Me; R3a and R3b are independently selected from H and Me; R4 is either H or Me; R5 is either H or Me; R6a and R6b are independently selected from H and Me; A is either (IIa), where R7a is selected from N-linked N-containing C5-7 heterocycyl and (A); or (ii) (IIb), where X is selected from CH2, N H and O, one of R8a and R8b is selected from CI and ethoxy and the other of R8a and R8b is H.
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PYRIDINE DERIVATIVES AND THIER USE IN THE TREATMENT OF CANCER AND HEMOGLOBINOPATHIES (Fri, 15 Sep 2017)
A compound of formula (Ia), (Ib) or (Ic) wherein: n is 1 or 2; RN is H or Me; R1 is optionally one or more halo or methyl groups; R2a and R2b are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R2c and R2d (if present) are independently selected from the group consisting of: (i) F; (ii) H; (iii) Me; and (iv) CH2OH; R3a and R3b are independently selected from H and Me; R4a is selected from OH, -NH2, -C(=O)NH2, and -CH2OH; R4b is either H or Me; R5 is either H or Me; A is either (i), where R6a is ether; or (ii),, where X is selected from CH2, NH and O, one of R7a and R7b is selected from CI and ethoxy and the other of R7a and R7b is H.
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IMIDAZO[4,5-C]QUINOLIN-2-ONE COMPOUNDS AND THEIR USE IN TREATING CANCER (Fri, 15 Sep 2017)
The specification generally relates to compounds of Formula (I): and pharmaceutically acceptable salts thereof, where R1 is tetrahydropyran-3-yl or 3,3-dimethyltetrahydropyran-4-yl; R2 is methyl or hydro; R3 is hydro or fluoro; R4 is hydro or fluoro; and R5 is methyl or hydro; the use of compounds of Formula (I) or pharmaceutically acceptable salts thereof to treat or prevent ATM mediated disease, including cancer; pharmaceutical compositions comprising substituted imidazo [4,5- c]quinolin-2-one compounds or pharmaceutically acceptable salts thereof; kits comprising compounds of Formula (I) or pharmaceutically acceptable salts thereof; methods of manufacture of compounds of Formula (I) or pharmaceutically acceptable salts thereof; and intermediates useful in such manufacture.
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BENZO[B]THIOPHENE DERIVATIVES AND THEIR USE FOR THE INHIBITION OF FIBROBLAST GROWTH FACTOR RECEPTOR KINASES (FGFRS) FOR THE USE OF NEO- AND HYPERPLASIA THERAPIES (Fri, 15 Sep 2017)
The present invention relates to benzo[b]thiophene derivatives of general formula (I) and pharmaceutically acceptable salts, solvates, hydrates, stereoisomeric and polymorphic forms thereof wherein R1 is selected from the group of hydrogen; hydroxyl; substituted or unsubstituted heterocyclyl; optionally substituted amino; X, Y and Z are selected independently from the followings: CH (methine), nitrogen; R2, R3, R4 and R5 may stand for e.g. hydrogen, halogen, hydroxyl, alkyl, alkenyl, alkynyl, alkoxy and amino. The invention also relates to the use of them as of medication, as well as pharmaceutical compositions containing at least one of them as pharmaceutically active agent(s) together with pharmaceutically acceptable carrier, excipient and/or diluent, especially for the inhibition Fibroblast Growth Factor Receptor kinases (FGFR's), e.g. for the treatment of cancer.
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5-SULFAMOYL-2-HYDROXYBENZAMIDE DERIVATIVES (Fri, 15 Sep 2017)
The invention is directed to substituted salicylamide derivatives. Specifically, the invention is directed to compounds according to Formula (I): wherein R, R1 and R2 are as defined herein, or a pharmaceutically acceptable salt thereof. The compounds of the invention are inhibitors of CD73 and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with CD73 inhibition, such as AIDS, the treatment of HIV, autoimmune diseases, infections, atherosclerosis, and ischemia–reperfusion injury. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting CD73 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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METHODS OF DIAGNOSING CANCER (Fri, 15 Sep 2017)
Disclosed are two methods of treating or preventing a proliferative disease as characterized and/or diagnosed by at least one selected from an accumulation of branched-chain amino acid (s) (BCAA), suppression of activity or transcripts level of BCAA catabolic enzyme(s) and a decrease in acylcarnitine level (C5:1 ), one comprising the administration of a BCAA catabolism enhancer and/or branched chain alpha-ketoacid dehydrogenase complex (BCKDC) kinase inhibitor and the other comprising administration of a meal replacement with low BCAA levels. In three separate embodiments, methods of diagnosis or prognosis are disclosed, each comprising the measurement of the levels of a different marker, i.e. BCAA, BCAA catabolic enzymes or acylcarnitine (C5:1 ). In preferred embodiments, the proliferative disease is cancer. Also disclosed is a kit or microarray chip useful for methods thereof.
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NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO (Fri, 15 Sep 2017)
This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.
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SUBSTITUTED HETEROCYCLES AS C-MYC TARGETING AGENTS (Fri, 15 Sep 2017)
Disclosed are substituted heterocycles compounds including substituted pyrazoles, substituted pyrimidines, and substitute triazoles. The substituted heterocycles disclosed herein are shown to be useful in inhibiting c-MYC and may be utilized as therapeutics for treating cancer and cell proliferative disorders.
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SMALL MOLECULE INDUCERS OF REACTIVE OXYGEN SPECIES AND INHIBITORS OF MITOCHONDRIAL ACTIVITY (Fri, 15 Sep 2017)
This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a quinazolinedione structure which function as reactive oxygen species (ROS) inducers and inhibitors of mitochondrial activity within cancer cells (e.g., pancreatic cancer cells), and their use as therapeutics for the treatment of cancer (e.g., pancreatic cancer) and other diseases.
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CYCLIC KETO-AMIDE COMPOUNDS AS CALPAIN MODULATORS AND METHODS OF PRODUCTION AND USE THEREOF (Fri, 15 Sep 2017)
The present technology relates to cyclic keto-amide compounds of general formulae I to XXXII, compositions and kits thereof as calpain modulators and methods useful for the treatment of various diseases or disorders such as fibrotic disease or cancer which are associated or mediated, by calpains, such as CAPN1, CAPN2, and/or CAPN9. The present technology is also applicable to cyclic keto-amide compounds which inhibit myofibroblast differentiation.
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HYPERPOLARIZED MICRO-NMR SYSTEM AND METHODS (Fri, 15 Sep 2017)
Described herein are micro-coil hyperpolarized NMR systems and methods for measuring metabolic flux in living and non-living samples. Such systems can perform high throughput measurements (with multiple coils) of metabolic flux without destroying the material, making it useful to analyze tumor biopsies, cancer stem cells, and the like. In certain embodiments, a hyperpolarized micromagnetic resonance spectrometer (HMRS), described herein, is used to achieve real-time, significantly more sensitive (e.g., 103-fold more sensitive) metabolic analyses of live cells or non-living samples. In this platform, a suspension mixed with hyperpolarized metabolites is loaded into a miniaturized detection coil (e.g., about 2 μL), where the flux analysis can be completed within a minute without significant changes in viability. The sensitive and rapid analytical capability of the provided systems enables rapid assessment of metabolic changes by a given drug, which may direct therapeutic choices in patients.
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CAMPTOTHECIN DERIVATIVES AND USES THEREOF (Fri, 15 Sep 2017)
Provided herein are camptothecin derivatives and pharmaceutical compositions thereof. In other embodiments, provided herein are methods of treatment, prevention, or amelioration of a variety of medical disorders such as, for example, cancer using the compounds and pharmaceutical compositions disclosed herein.
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HETEROCYCLIC INHIBITORS OF PTPN11 (Fri, 15 Sep 2017)
The present invention relates to compounds which may be useful as inhibitors of PTPN11 for the treatment or prevention of cancer and other PTP-mediated diseases. The compounds are based on various substituted ring-fused pyrimidin-4-ones.
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ANTI-CANCER AND SPLCE MODULATING COMPOUNDS AND METHODS (Fri, 15 Sep 2017)
There are provided inter alia stable anti-cancer compounds and splice modulators and methods of synthesis and use thereof.
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INHIBITORS OF CREB-CBP INTERACTION FOR TREATMENT OF LEUKEMIA (Fri, 15 Sep 2017)
Compounds and methods are provided for inhibiting a CREB-CBP protein-protein interaction in a sample. In some cases, the method includes modulating transcription of CREB in a cell that overexpresses CREB. Also provided are methods of inhibiting the proliferation of a cancer cell. The subject CREB transcription inhibitor compounds include a substituted salicylamide or a prodrug thereof. Methods of alleviating symptoms associated with cancer (e.g., Acute Myeloid Leukemia (AML) or Acute Lymphomblastic Leukemia (ALL)) in a subject in need thereof are also provided. Pharmaceutical compositions including the subject compounds find use in treating cancer. The subject compounds may be formulated or provided to a subject in combination with a second agent, e.g. an anticancer agent.
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AURORA KINASE AND JANUS KINASE INHIBITORS FOR PREVENTION OF GRAFT VERSUS HOST DISEASE (Fri, 15 Sep 2017)
Disclosed herein are compounds and methods for reducing the risk of developing, preventing, or treating graft versus host disease (GVHD) in a subject. The compounds can concurrently block Aurora kinase A and JAK2 signal transduction which synergistically suppresses alloreactive human T-cells in vitro, prevents xenogeneic graft- versus-host disease without impairing anti-tumor responses, and promotes the development and suppressive potency of CD39+ inducible Treg. In certain aspects, disclosed are compounds of Formula I-V.
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INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE (Fri, 15 Sep 2017)
The invention relates to a compound of Formula (I), or pharmaceutically acceptable enantiomers, or salts thereof. The present invention also relates to the use of compounds of Formula (I) as selective inhibitors of indoleamine 2,3-dioxygenase. The invention also relates to the use of the compounds of Formula (I) for the treatment or prevention of diseases cancer, infections, central nervous system disease or disorder, and immune-related disorders, either as a single agent or in combination with other therapies.
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COMPOSITE NANOPARTICLES AND USES THEREOF (Fri, 15 Sep 2017)
Provided herein are composite nanoparticles, methods of making composite nanoparticles and methods of using composite nanoparticles to treat or ameliorate various diseases, such as, for example, cancer.
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Bromodomain inhibitors (Fri, 15 Sep 2017)
2 3 4 1 2 The present invention provides for compounds of formula (I) wherein A1 , A , A , A , X , X , Y L', G1 , R', and R1 have any of the values defined thereof in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).
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BICYCLIC UREA, THIOUREA, GUANIDINE AND CYANOGUANIDINE COMPOUNDS USEFUL FOR THE TREATMENT OF PAIN (Fri, 15 Sep 2017)
[0010131 Compounds of Formula I: or stereoisomers, tautomers, or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein Ring A, Ring C and X are as defined herein, are inhibitors of TrkA kinase and are useful in the treatment of diseases which can be treated with a TrkA kinase inhibitor such as pain, cancer, inflammation/inflammatory diseases, neurodegenerative diseases, certain infectious diseases, Sjogren's syndrome, endometriosis, diabetic peripheral neuropathy, prostatitis and pelvic pain syndrome.
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VIRUS VECTORS EXPRESSING MULTIPLE EPITOPES OF TUMOR ASSOCIATED ANTIGENS FOR INDUCING ANTITUMOR IMMUNITY (Sat, 09 Sep 2017)
Provided are polynucleotides and viral vectors, particularly, alphavirus vectors such as Sindbis viral vectors, which encode multiple, e.g., two or more, epitopes of at least one tumor associated antigen in which each epitope is separated by a processing or enzyme cleavage site. The multiple epitopes of the two or more tumor associated antigens encoded by the described polynucleotides and viral vectors may be the same or different. Methods of treating mammalian subjects having a cancer or tumor expressing the tumor associated antigen epitopes are provided, in which the viral vectors encoding the multiple epitopes, as well as other immunostimulatory or immunomodulatory components, generate an anti-cancer or anti-tumor immune response in which high levels of effector T cells increase the survivability of tumored mammalian subjects and result in epitope spreading, thus providing a further enhancement of the immune response.
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1-(PYRIMIDIN-2-YL)-1H-INDAZOLES HAVING BUB1 KINASE INHIBITING ACTIVITY (Sat, 09 Sep 2017)
The present invention relates to Bub1 kinase (= Budding uninhibited by benzimidazole kinase) inhibiting 1-(pyrimidin-2-yl)-1H-indazole compounds of formula (I), i.e. which therefore have potential to treat hyperprofilerative diseases such as cancer.
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ANTIBODIES TO CD40 WITH ENHANCED AGONIST ACTIVITY (Sat, 09 Sep 2017)
Provided herein are agonistic antibodies, or antigen binding portions thereof, that bind to human CD40. Such antibodies optionally comprise Fc regions with enhanced specificity for FcϒRIIb. The invention also provides methods of treatment of cancer or chronic infection by administering the antibodies of the invention to a subject in need thereof.
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HSP90 INHIBITOR DRUG CONJUGATES (Sat, 09 Sep 2017)
The present invention provides Hsp90 drug conjugates (HDCs) comprising an Hsp90 ligand or prodrug thereof, a linker moiety and a payload moiety. The invention also provides methods for treating a disease or disorder in a subject, for example cancer, with an HDC.
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THERAPEUTIC AND DIAGNOSTIC METHODS FOR CANCER (Sat, 09 Sep 2017)
The present invention provides therapeutic and diagnostic methods and compositions for cancer, for example, bladder cancer. The invention provides methods of treating bladder cancer, methods of determining whether a patient suffering from bladder cancer is likely to respond to treatment comprising a PD-L1 axis binding antagonist, methods of predicting responsiveness of a patient suffering from bladder cancer to treatment comprising a PD-L1 axis binding antagonist, and methods of selecting a therapy for a patient suffering from bladder cancer, based on somatic mutation levels of genes of the invention (e.g., somatic mutation levels in a tumor sample obtained from the patient).
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STAPLED INTRACELLULAR-TARGETING ANTIMICROBIAL PEPTIDES TO TREAT INFECTION (Sat, 09 Sep 2017)
Structurally stabilized, e.g., stapled, peptides with the ability to translocate through microbial cell membranes to the interior of microbial cells and exert a biological activity there are provided, as are methods of designing, making and using such peptides.
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ENHANCED CANCER IMMUNOTHERAPY BY MICRONEEDLE PATCH-ASSISTED DELIVERY (Sat, 09 Sep 2017)
Disclosed herein are self-degradable microneedle devices for the controlled-release of an immunotherapeutic agent. Also disclosed are methods for treating a disease (for example, cancer) using a self-degradable microneedle patch for the sustained delivery of an immunotherapeutic agent (for example, a PD1 antibody).
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IMMUNOMODULATORS (Sat, 09 Sep 2017)
The present disclosure provides novel macrocyclic compounds which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.
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STING ACTIVATING NANOVACCINE FOR IMMUNOTHERAPY (Sat, 09 Sep 2017)
In some aspects, the present disclosure provides vaccine compositions comprising an antigen and a diblock copolymer wherein the diblock copolymer is pH responsive. In some embodiments, these compositions activate the STING and/or the interferon receptor pathways. In some embodiments, the diblock copolymer has a pKa from about 6 to about 7.5. Also provided herein are methods of treatment using these compositions to treat an infectious disease or cancer.
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ERIBULIN-BASED ANTIBODY-DRUG CONJUGATES AND METHODS OF USE (Sat, 09 Sep 2017)
Linker toxins and antibody-drug conjugates that bind to human oncology antigen targets such as folate receptor alpha and/or provide anti-tubulin drug activity are disclosed. The linker toxins and antibody-drug conjugates comprise an eribulin drug moiety and can be internalized into target antigen-expressing cells. The disclosure further relates to methods and compositions for use in the treatment of cancer by administering the antibody-drug conjugates provided herein.
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NOVEL OXAZOLE AND THIAZOLE COMPOUNDS AS Β-CATENIN MODULATORS AND USES THEREOF (Sat, 09 Sep 2017)
Heterocyclic compounds according to formula I: wherein A, B, Y, and Cy are as described herein, are provided as inhibitors of the Wnt pathway that specifically target the activity of the stabilized pool of B-cat. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, cancer, and other conditions related to Wnt pathway dysfunction, including various cancers and pulmonary fibrosis.
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SUBSTITUTED INDOLE MCL-1 INHIBITORS (Sat, 09 Sep 2017)
The present disclosure provides for compounds that inhibit the activity of an anti- apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present disclosure also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over- expression or dysregulation of Mcl-1 protein.
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SPIRO-CONDENSED PYRROLIDINE DERIVATIVES AS DEUBIQUITYLATING ENZYMES (DUB) INHIBITORS (Sat, 09 Sep 2017)
The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of Cezanne 1. The invention further relates to the use of DUB inhibitors in the treatment of cancer. (Figure (I))
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4,9-DIOXO-4,9-DIHYDRONAPHTHO(2,3-B)FURAN-3-CARBOXAMIDE DERIVATIVES AND USES THEREOF FOR TREATING PROLIFERATIVE DISEASES AND INFECTIOUS DISEASES (Sat, 09 Sep 2017)
The present disclosure provides compounds of Formulas (I), (II), and pharmaceutically acceptable salts thereof. The compounds described herein are useful in treating proliferative diseases, for example, cancer (e.g., lung cancer), and infectious diseases (e.g., bacterial infections).
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ARYL-OR HETEROARYL-SUBSTITUTED BENZENE COMPOUNDS (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present invention relates to aryl- or heteroaryl-substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.</p>
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IMMUNOMODULATORS (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present disclosure provides novel macrocyclic compounds which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.</p>
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ERIBULIN-BASED ANTIBODY-DRUG CONJUGATES AND METHODS OF USE (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">Linker toxins and antibody-drug conjugates that bind to human oncology antigen targets such as folate receptor alpha and/or provide anti-tubulin drug activity are disclosed. The linker toxins and antibody-drug conjugates comprise an eribulin drug moiety and can be internalized into target antigen-expressing cells. The disclosure further relates to methods and compositions for use in the treatment of cancer by administering the antibody-drug conjugates provided herein.</p>
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4-OXO-N-(4-HYDROXYPHENYL)RETINAMIDE DERIVATIVES AS THERAPEUTIC AGENTS FOR THE TREATMENT OF CANCER (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present invention relates to a compound having formula (I) below or a pharmaceutically acceptable salt thereof:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="43.52mm" wi="73.15mm" file="US20170253560A1-20170907-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein:</p> <p id="p-0004" num="0000">X is —COOH or NH<sub>2</sub>;</p> <p id="p-0005" num="0000">R is a straight or branched C<sub>1</sub>-C<sub>10 </sub>alkylene chain; and</p> <p id="p-0006" num="0000">R<sub>1 </sub>is H, straight or branched C<sub>1</sub>-C<sub>10 </sub>alkyl, aryl, or R<sub>2</sub>CO— wherein R<sub>2 </sub>is straight or branched C<sub>1</sub>-C<sub>10 </sub>alkyl, for use as antitumoral agents.</p>
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SUBSTITUTED HETEROCYCLES AS c-MYC TARGETING AGENTS (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">Disclosed are substituted heterocycles compounds including substituted pyrazoles, substituted pyrimidines, and substitute triazoles. The substituted heterocycles disclosed herein are shown to be useful in inhibiting c-MYC and may be utilized as therapeutics for treating cancer and cell proliferative disorders.</p>
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PYRIMIDINE COMPOUNDS AND PYRIMIDO INDOLE COMPOUNDS AND METHODS OF USE (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present invention discloses a compound comprising the formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.89mm" wi="53.51mm" file="US20170253612A1-20170907-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R is hydrogen or an alkyl group having from one to ten carbon atoms, or a compound of the formula wherein the S is replaced by CH<sub>2</sub>, and optionally comprising a pharmaceutically acceptable salt, hydrate, or solvate thereof. A method of treating a patient having cancer or a disease comprising administering to a patient an effective amount of the compound or pharmaceutically acceptable salt, hydrate, or solvate thereof.</p>
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