Cancer

USL-311 FOR USE IN THE TREATMENT OF CANCER (Fri, 14 Sep 2018)
The invention relates to the use of the CXCR4 antagonist 6-{4-[1-(Propan-2- yl)piperidin-4-yl]-1,4-diazepan-1-yl}-N-(pyridin-4-yl)pyridine-2-carboxamide or a pharmaceutically acceptable salt thereof in the treatment of cancers of the breast, bladder, colon, rectum and liver.
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PYRIMIDOPYRIMIDINONES USEFUL AS WEE-1 KINASE INHIBITORS (Fri, 14 Sep 2018)
The present invention relates to a compound that is useful as an inhibitor of the activity of Wee-1 kinase. The present invention also relates to pharmaceutical compositions comprising this compound and to methods of using this compound in the treatment of cancer and methods of treating cancer.
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CYCLIC SUBSTITUTED IMIDAZO[4,5-C]QUINOLINE DERIVATIVES (Fri, 14 Sep 2018)
The present invention provides novel cyclic substituted imidazo[4,5- c]quinoline derivatives of Formula (I), and the pharmaceutically acceptable salts thereof, wherein R1, R2, R4, R5, R6, X and Z are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of Formula I and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.
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NOVEL IMIDAZO[4,5-C]QUINOLINE DERIVATIVES AS LRRK2 INHIBITORS (Fri, 14 Sep 2018)
The present invention provides novel imidazo[4,5-c]quinoline derivatives of Formula (I), and the pharmaceutically acceptable salts thereof I wherein R1, R2 and R3 are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of Formula I and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.
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COMPOSITIONS AND METHODS FOR TREATING CANCER (Fri, 14 Sep 2018)
A method of treating a malignant disease in a subject in need thereof is provided. The method comprising administering to the subject a therapeutically effective amount of a first liquid chromatography fraction of a cannabis extract comprising at least 75 % tetrahydrocannabinolic acid (THCA), and a therapeutically effective amount of a second liquid chromatography fraction of a cannabis extract comprising at least 75 % cannabigerolic acid (CBGA), wherein the first liquid chromatography fraction comprises cannabis derived active ingredients other than the THCA, and the second liquid chromatography fraction comprises cannabis derived active ingredients other than the CBGA, thereby treating the malignant disease in the subject.
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CATHEPSIN-D AND ANGIOGENESIS INHIBITORS AND COMPOSITIONS THEREOF FOR TREATING BREAST CANCER (Fri, 14 Sep 2018)
The invention relates to Cathepsin-D and angiogenesis inhibitors and compositions thereof for treating breast cancer. More particularly, the invention relates to the design and synthesis of inhibitors of Cathepsin D which exhibits antiproliferative activity and also inhibits angiogenesis. The present invention also relates to the compositions thereof for treating breast cancer.
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INHIBITORS OF MALT1 AND USES THEREOF (Fri, 14 Sep 2018)
Provided herein are compounds that inhibit MALTl, a protein whose activity is responsible for constitutive NF-κΒ signaling in certain cancers (e.g., activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL)). Also provided are pharmaceutical compositions and kits comprising the compounds, and methods of treating MALTl -related diseases and disorders (e.g., cancer) with the compounds in a subject, by administering the compounds and/or compositions described herein.
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INDOLE AND INDAZOLE COMPOUNDS AND THERAPEUTIC USES THEREOF (Fri, 14 Sep 2018)
Disclosed are Indole and Indazole urea derivative compounds, methods for preparing these compounds, and methods for treating cancer.
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THERAPEUTIC COMPOUNDS AND METHODS (Fri, 14 Sep 2018)
Disclosed herein are compounds of formula II: II or a salt thereof. Also disclosed are pharmaceutical compositions and therapeutic methods for treating certain diseases including cancer such as lung cancer.
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WARHEAD-CONTAINING PEPTIDOMIMETIC MACROCYCLES AS MODULATORS OF BFL-1 (Fri, 14 Sep 2018)
The disclosed peptidomimetic macrocycles modulate the activity of BFL-1 or a BCL-2 family protein. BFL-1, an anti-apoptotic BCL-2 family member, blocks p53-mediated apoptosis and has oncogenic transforming activity. Peptidomimetic macrocycles, pharmaceutical compositions, and methods disclosed herein can be used for the treatment of disease in which BFL-1 or a BCL-2 family protein is over-expressed, such as cancer. In particular, BFL-1-modulating or a BCL-2 family protein-modulating peptidomimetic macrocycles disclosed herein can be applied in the setting of resistance to BCL-2 family inhibitors, which is often engendered by BFL-1 or BCL-2 family protein over-expression or hyper-activation.
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1H-pyrazolo[3,4-b]pyridines and therapeutic uses thereof (Wed, 12 Sep 2018)
<p id="p-0001" num="0000">Provided herein are compounds according to Formulas (I) or (II) and pharmaceutically acceptable salts thereof, and compositions comprising the same, for use in various methods, including treating cancer, abnormal cellular proliferation, angiogenesis, Alzheimer's disease, lung disease, osteoarthritis, idiopathic pulmonary fibrosis and neurological conditions/disorders/diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="96.10mm" wi="69.85mm" file="US10071086-20180911-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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HALOALLYLAMINE PYRAZOLE DERIVATIVE INHIBITORS OF LYSYL OXIDASES AND USES THEREOF (Sat, 08 Sep 2018)
The present invention relates to novel compounds which are capable of inhibiting certain amine oxidase enzymes. These compounds are useful for treatment of a variety of indications, e.g., fibrosis, cancer and/or angiogenesis in human subjects as well as in pets and livestock. In addition, the present invention relates to pharmaceutical compositions containing these compounds, as well as various uses thereof.
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CRYSTALLINE FORMS OF SALTS OF FUSED TERA OR PENTA-CYCLIC DIHYDRODIAZEPINOCARAZOLONES, AND USES THEREOF (Sat, 08 Sep 2018)
Disclosed herein are salts of (R) -2-fluoro-10a-methyl-7, 8, 9, 10, 10a, 11-hexahydro-5, 6, 7a, 11-tetraazacyclohepta [def] cyclopenta [a] fluoren-4 (5H) -one, and crystalline forms (polymorphs) thereof. Also disclosed herein are methods of preparing those crystalline forms, and methods of using at least one of those crystalline forms in treating a cancer responsive to inhibition of PARP, especially a cancer associated with BRCA1/2 mutant activities or other HR deficiencies, in a subject.
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ANTIBODIES HAVING SPECIFICITY TO NECTIN-4 AND USES THEREOF (Sat, 08 Sep 2018)
The present invention relates to a new antibody anti-nectin-4. Nectin-4 is a tumor-associated antigen overexpressed in several cancers and notably in 30%, 49% and 86% of breast, ovarian and lung carcinomas, respectively, which are tumors of bad prognosis. Treatments remain still elusive. That's why the inventors developed a new targeted therapy based on an antibody having specificity to nectin-4 (called 14A5.2 mab). Indeed, the inventors selected this antibody for its intrinsic prophylactic anti-metastatic properties and also for the treatment of localized primary and metastatic cancer. More, the 14A5.2 mab could be indicated for the treatment of cancer resistant to ASG-22ME (from Astellas company). Thus, the invention relates to the 14A5.2 mab and its uses thereof.
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BORONATED MULTIFUNCTIONAL TARGETING DRUG CONJUGATES, THEIR USES AND METHODS FOR THEIR PREPARATION (Sat, 08 Sep 2018)
Tri-component multi-functional boronated complexes (B-complexes), featuring reversible covalent bonds, are described, which incorporate a drug;a water-soluble moiety (e.g. polyethylene glycol (PEG) chains, cyclodextrins);and a targeting unit. A B- complex core was assembled in one step, and proved to be stable in different biocompatible conditions, such as human plasma, though reversible for example in the presence of glutathione (GSH). This platform enabled the modular construction of the multifunctional conjugates exhibiting high selectivity towards, for example, folate- receptor-positive MDA-MB-231 cancer cells, having an IC50 in the low nanomolar range.
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METHOD OF PREDICTING EFFECTS OF CDC7 INHIBITOR (Sat, 08 Sep 2018)
The present invention relates to a method of predicting the likelihood that a patient will respond therapeutically to a pancreatic cancer treatment comprising the administration 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 (Compound 1) and/or tautomers thereof or a pharmaceutically acceptable salt or hydrate thereof, comprising the steps of: STEP (1): determining a KRAS gene mutation status of a sample from a patient, and STEP (2): predicting an increased likelihood that the patient will respond therapeutically to the pancreatic cancer treatment if the patient has the presence of KRAS gene mutation(s), and to methods of treating pancreatic cancer.
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PHARMACEUTICALLY ACCEPTABLE SALTS OF B-GUANIDINOPROPIONIC ACID WITH IMPROVED PROPERTIES AND USES THEREOF (Sat, 08 Sep 2018)
The present invention relates to new pharmaceutical salts of β-GPA which exhibit improved physical properties. In particular, the invention relates to salts of β-GPA with improved flow properties (e.g., improved Carr's index and/or Hausner ratio) such as fumarate salts, succinate salts, and oxalate salts. The invention also relates to pharmaceutical compositions including a pharmaceutically effective amount of one or more salts of β-GPA, as well as methods of treating cancer including administration of a formulation including a β-GPA salt of the invention to a subject in need thereof.
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COMPOSITIONS AND METHODS FOR CAR T CELL THERAPY (Sat, 08 Sep 2018)
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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SHP INHIBITOR COMPOSITIONS AND USES FOR CHIMERIC ANTIGEN RECEPTOR THERAPY (Sat, 08 Sep 2018)
Compositions and methods for treating diseases associated with expression of a cancer associated antigen are disclosed. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen as described herein, SHP inhibitory molecules, vectors encoding the same, and recombinant immune effector cells comprising the CARs and SHP inhibitory molecules. Methods of administering a genetically modified immune effector cell expressing a CAR that comprises an antigen binding domain that binds to a cancer associated antigen and a SHP inhibitory polypeptide are also disclosed.
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USES OF PYRIMIDOPYRIMIDINONES AS SIK INHIBITORS (Sat, 08 Sep 2018)
The present disclosure provides methods of increasing skin pigmentation in a subject in need thereof using salt-inducible kinase (SIK) inhibitors, such as macrocyclic compounds of Formula (I), bicyclic urea compounds of Formula (II), (III), and (IV), and compounds of Formula (V), (VI), (VI-A), or (VII). Also provided are pharmaceutical compositions, methods, and uses that include or involve a compound described herein.
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DIAGNOSTIC AND THERAPEUTIC METHODS FOR CANCER (Sat, 08 Sep 2018)
The present invention provides diagnostic methods, therapeutic methods, and compositions for the treatment of cancer (e.g., kidney cancer (e.g., renal cell carcinoma (RCC)), lung cancer (e.g., non-small cell lung cancer (NSCLC)), bladder cancer (e.g., urothelial bladder cancer (UBC)), liver cancer (e.g., hepatocellular carcinoma (HCC)), ovarian cancer, or breast cancer (e.g., triple-negative breast cancer (TNBC))). The invention is based, at least in part, on the discovery that expression levels of one or more biomarkers described herein in a sample from an individual having cancer can be used in methods of predicting the therapeutic efficacy of treatment with a VEGF antagonist (e.g., an anti-VEGF antibody, (e.g., bevacizumab) or a VEGFR inhibitor (e.g., a multi-targeted tyrosine kinase inhibitor (e.g., sunitinib, axitinib, pazopanib, or cabozantinib))) and a PD-L1 axis binding antagonist (e.g., a PD-L1 binding antagonist (e.g., anti-PD-L1 antibody, e.g., atezolizumab (MPDL3280A)) or a PD-1 binding antagonist (e.g., anti-PD-1 antibody)), or with an angiogenesis inhibitor (e.g., a VEGF antagonist (e.g., a VEGFR inhibitor, (e.g., a multi-targeted tyrosine kinase inhibitor (e.g., sunitinib, axitinib, pazopanib, or cabozantinib)))).
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INDOLINONE DERIVATIVES AS INHIBITORS OF MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE (Sat, 08 Sep 2018)
The present disclosure relates to indolinone compounds, compositions, and methods for the inhibition of maternal embryonic leucine zipper kinase (MELK). The present disclosure further relates to indolinone compounds, compositions, and methods for the treatment or prevention of a cancer (for example, triple negative breast cancer).
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NOVEL ANTI-INFECTIVE AND ANTI-INFLAMMATORY COMPOUNDS (Sat, 08 Sep 2018)
Lysosomally accumulated substances that release a nitroxy group, or a short chain fatty acid or a product of anaerobic metabolism or a thiol or a sulfide often from an ester or similar labile linkage have anti-inflammatory, anti-cancer and anti-bacterial activity. They are useful in treating infectious, inflammatory and malignant disease.
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INDUCTION AND ENHANCEMENT OF ANTITUMOR IMMUNITY INVOLVING VIRUS VECTORS EXPRESSING MULTIPLE EPITOPES OF TUMOR ASSOCIATED ANTIGENS AND IMMUNE CHECKPOINT INHIBITORS OR PROTEINS (Sat, 08 Sep 2018)
Provided are polynucleotides and viral vectors, e.g., alphavirus or Sindbis viral vectors, encoding 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 encoded epitopes may be the same or different. Also provided are polynucleotides and viral vectors, particularly, alphavirus or Sindbis viral vectors, encoding an immune checkpoint protein, or a ligand binding portion thereof. The immune checkpoint protein or ligand binding portion thereof may be fused to immunoglobulin domains, e.g., an Ig hinge domain and an Ig heavy chain constant domain. Methods of treating subjects having a cancer or tumor, e.g., a TAA-expressing tumor, with the described viral vectors are provided. Treatment of subjects with the vectors, the checkpoint inhibitor molecules and/or other immunomodulatory components, generate an anti-cancer or anti-tumor immune response resulting in increased survivability of tumored subjects and epitope spreading.
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APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein.</p>
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HETEROCYCLIC CONSTRAINED TRICYCLIC SULFONAMIDES AS ANTI-CANCER AGENTS (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">A genus of arylsulfonamide derivatives of heterocyclic constrained tricyclic compounds is disclosed. The compounds are of the following genus:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.24mm" wi="52.15mm" file="US20180251444A1-20180906-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The compounds induce FOXO1 transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a therapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.</p>
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DNA BINDING AGENTS WITH A MINOR GROOVE BINDING TAIL (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">Provided herein are compounds which intercalate into the DNA of a cell and are capable of crossing the blood brain barrier of a formula provided herein. Pharmaceutical compositions of the compounds and methods of treating cancer, for example brain, lung, or pancreatic cancer, are also provided herein.</p>
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HETEROCYCLIC CONSTRAINED TRICYCLIC SULFONAMIDES AS ANTI-CANCER AGENTS (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">A genus of arylsulfonamide derivatives of heterocyclic constrained tricyclic compounds is disclosed. The compounds are of the following genus:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.04mm" wi="47.41mm" file="US20180251456A1-20180906-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The compounds induce FOXO1 transcription factor translocation to the nucleus by modulating PP2A and, as a consequence, exhibit anti-proliferative effects. They are useful in the treatment of a variety of disorders, including as a therapy in cancer treatment, or used in combination with other drugs to restore sensitivity to chemotherapy where resistance has developed.</p>
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HISTONE DEMETHYLASE INHIBITORS (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">The present disclosure relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted pyridine 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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1,5-DISUBSTITUTED 1,2,3-TRIAZOLES ARE INHIBITORS OF RAC/CDC42 GTPASES (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">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.</p>
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HETEROCYCLIC COMPOUNDS AND USES THEREOF (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">The present invention relates to pharmaceutical compounds, compositions and methods, especially as they are related to compositions and methods for the treatment and/or prevention of a proliferation disorder, a cancer, a tumor, an inflammatory disease, an autoimmune disease, psoriasis, dry eye or an immunologically related disease, and in some embodiments diseases or disorders related to the dysregulation of kinase such as, but not limited to, EGFR (including HER), Alk, PDGFR, BLK, BMX/ETK, FLT3(D835Y), ITK, TEC, TXK, BTK, or JAK, and the respective pathways.</p>
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METHOD FOR INDUCING CYTOTOXICITY IN CANCER CELLS (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">A method for treating a proliferative disease, disorder, or condition comprising administering a gold(III) complex such as [Au(npen)Cl<sub>2</sub>]Cl.2H<sub>2</sub>O (1) or [Au(npen)<sub>2</sub>]Cl<sub>3 </sub>(2); the complexes, and methods for making them.</p>
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MALT1 INHIBITORS AND USES THEREOF (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">Provided herein are compounds of Formula (I) and pharmaceutical compositions thereof, which may be useful as MALT1 inhibitors. Also provided are for the treatment of proliferative disorders (e.g., cancer (e.g., non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, MALT, lymphoma), benign neoplasm, a disease associated with angiogenesis, an autoimmune disease, an inflammatory disease, an autoinflammatory disease) by administering a compound of Formula (I).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="44.70mm" wi="69.85mm" file="US20180251489A1-20180906-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Urinary Polyamines as Prostate Cancer Detection Biomarkers (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">The present disclosure relates to urinary polyamines useful as prostate cancer biomarkers and a sensitive and specific, method for detecting and quantifying urinary polymaines using lanthanide complexes.</p>
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BIOTINYLATED LUMINESCENT PROBE (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">Provided herein are luminescent probes of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="53.42mm" wi="76.20mm" file="US20180252718A1-20180906-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and complexes thereof for the detection of cancer cells.</p>
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MIT BIOMARKERS AND METHODS USING THE SAME (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">Provided are therapies related to the treatment of pathological conditions, such as cancer.</p>
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3-(1H-IMIDAZO[4,5-C]PYRIDIN-2-YL)-1H-PYRAZOLO[3,4-C]PYRIDINE AND THERAPEUTIC USES THEREOF (Fri, 07 Sep 2018)
<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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PROTEIN KINASE INHIBITORS (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">A compound of formula (I), wherein R<sub>3</sub>, R<sub>4</sub>, G, B, M, and Z are as defined in the claims, and pharmaceutically acceptable salts thereof are disclosed. The compounds of formula (1) possess utility as FGFR inhibitors and are useful in the treatment of a condition, where FGFR kinase inhibition is desired, such as cancer.</p>
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COMBINATION OF RIBOCICLIB AND DABRAFENIB FOR TREATING OR PREVENTING CANCER (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">The present disclosure relates to pharmaceutical combinations comprising a cyclin dependent kinase 4/6 (CDK4/6) inhibitor compound, (b) a B-Raf inhibitor compound, and optionally (c) an alpha-isoform specific phosphatidylinositol 3-kinase (PI3K) inhibitor compound, for the treatment or prevention of cancer, as well as related pharmaceutical compositions, uses, and methods of treatment or prevention of cancer.</p>
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TGF BETA RECEPTOR ANTAGONISTS (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">The invention relates generally to compounds of formula (I) that modulate the activity of TGFβR-1 and TGFβR-2, pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="44.70mm" wi="59.77mm" file="US20180250303A1-20180906-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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METHODS AND REAGENTS FOR RADIOLABELING (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">The present invention provides methods for radiolabeling compounds useful as Hsp90 inhibitors. The present invention also provides intermediates useful in such methods, and compositions of radiolabeled compounds. The present invention provides, among other things novel methods for the synthesis of radiolabeled compounds. In certain embodiments, the present invention provides compounds of formula I.</p>
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SYNTHETIC ANTIBODIES TO BAX AND USES THEREOF (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">Synthetic fragment antigen-binding (Fab) antibodies are disclosed that bind to an N-terminal activation site of BCL-2-associated X-protein (BAX) and inhibit BAX activation. Also disclosed are methods of using the Fabs for measuring inactive monomeric BAX levels, screening for small molecules that bind to an N-terminal activation site of BAX, inhibiting apoptotic cell death, and predicting the ability of a cancer therapy to promote apoptotic cell death.</p>
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ANTIBODY DRUG CONJUGATES (ADC) THAT BIND TO 158P1D7 PROTEINS (Fri, 07 Sep 2018)
<p id="p-0001" num="0000">Antibody drug conjugates (ADC's) that bind to 158P1D7 protein and variants thereof are described herein. 158P1D7 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in glioblastoma, lung cancer, bladder cancer, and breast cancer. Consequently, the ADC's of the invention provide a therapeutic composition for the treatment of cancer.</p>
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ANDROGEN RECEPTOR MODULATING COMPOUNDS (Thu, 06 Sep 2018)
Compounds of formula (I) wherein R 1 to R 16 , A. B and E are as defined in the claims and pharmaceutically acceptable salts and esters thereof, are disclosed. The compounds of formula ( I ) possess utility as tissue-selective androgen receptor modulators (SARM) and are particularly useful as medicaments in the treatment of prostate cancer and other AR dependent conditions and diseases where AR antagonism is desired.
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NEW CYTIDINE DERIVATIVE DIMERS AND APPLICATIONS THEREOF (Thu, 06 Sep 2018)
The present disclosure provides cytidine derivative dimers, salts and compositions of the cytidine derivative dimers, and methods of making and using the cytidine derivative dimers that are useful for treating a neoplasm in mammalian subjects. A cytidine derivative dimer may have the following general formula (I): By molecularly designing such cytidine-based compounds, the disclosed cytidine-based derivative dimers/salts show significant inhibiting effects on HCT-116 human colon cancer cells, and exhibit strong growth inhibiting effects on HCT-116 human colon cancer xenografts grown in nude mice. The disclosed cytidine derivative dimers/salts provide high anti-tumor activity with low toxicity and are useful for treating cancers.
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Abietic acid derivatives as anti-tumor agents (Wed, 05 Sep 2018)
<p id="p-0001" num="0000">The abietic acid derivatives as anti-tumor agents are derivatives of abietic acid in which the hydroxyl entity (—OH) of the carboxyl entity is replaced by an electronegative substituent, which may be C6H5-O—, C6H5-S—, or C6H5-NH—, and a hydrogen atom on one of the rings is replaced by a hydroxyl (—OH) substituents, the derivatives having the formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="77.05mm" wi="61.64mm" file="US10064837-20180904-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein X is O, S, or NH. The derivatives are formed by formation of an intermediate lactone from abietic acid, followed by reaction of the lactone with phenol, thiophenol, or aniline. All of the derivatives exhibited potent 5α-reductase inhibitor activity, both in vitro and in vivo, and anti-tumor activity with regard to two prostate cancer cell lines—LNCaP and PC-3. The intermediate lactones are also derivatives of abietic acid that exhibit anti-tumor activity. </p>
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Method of preparing glucosylceramide synthase inhibitors (Wed, 05 Sep 2018)
<p id="p-0001" num="0000">The invention relates to a method of preparing inhibitors of glucosylceramide synthase (GCS) useful for the treatment metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, and for the treatment of cancer.</p>
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PHARMACEUTICALLY ACCEPTABLE SALTS OF B-GUANIDINOPROPIONIC ACID WITH IMPROVED PROPERTIES AND USES THEREOF (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to new pharmaceutical salts of β-GPA which exhibit improved physical properties. In particular, the invention relates to salts of β-GPA with improved flow properties (e.g., improved Carr's index and/or Hausner ratio) such as fumarate salts, succinate salts, and oxalate salts. The invention also relates to pharmaceutical compositions including a pharmaceutically effective amount of one or more salts of β-GPA, as well as methods of treating cancer including administration of a formulation including a β-GPA salt of the invention to a subject in need thereof.</p>
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ANTI-CANCER AGENT COMPRISING AMINOACETONITRILE COMPOUND AS ACTIVE INGREDIENT (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to an anticancer agent having a high safety and a superior anticancer activity, and anticancer agent containing, as an active ingredient, an aminoacetonitrile compound represented by the formula (I) wherein R<sup>1 </sup>is a hydrogen atom, an alkyl group and the like, R<sup>2</sup>, R<sup>3</sup>, and R<sup>4 </sup>are the same or different and each is a hydrogen atom, an alkyl group and the like, R<sup>5 </sup>and R<sup>6 </sup>are the same or different and each is a hydrogen atom, a halogen atom and the like, m is 0 or 1, R is a halogen atom, a cyano group, a nitro group, a phenyl group optionally substituted by an alkyl group and the like, an alkyl group and the like, Ar<sup>1 </sup>is a phenyl group, a naphthyl group, a pyridyl group, a pyrazolyl group, or the like, each of which is optionally substituted by a halogen atom, a cyano group, a nitro group, alkyl group and the like, and W is —O—, —S—, —SO<sub>2</sub>—, or —N(R<sup>7</sup>)— wherein R<sup>7 </sup>is a hydrogen atom, a (C<sub>1</sub>-C<sub>6</sub>)alkyl group and the like, or a pharmacologically acceptable salt thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="18.80mm" wi="69.85mm" file="US20180243255A1-20180830-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PHARMACEUTICAL COMBINATION COMPRISING THE PI3K INHIBITOR ALPELISIB AND THE B-RAF INHIBITOR DABRAFENIB; THE USE OF SUCH COMBINATION IN THE TREATMENT OR PREVENTION OF CANCER (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">The present disclosure relates to a pharmaceutical combination comprising (a) alpha-isoform specific PI3K inhibitor and (b) a B-RAF inhibitor; combined preparations and pharmaceutical compositions thereof; the uses of such combination in the treatment or prevention of cancer; and methods of treating or preventing cancer in a subject comprising administering a therapeutically effective amount of such combination.</p>
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A PHARMACEUTICAL COMBINATION COMPRISING THE PI3K INHIBITOR ALPELISIB AND THE CDK4/6 INHIBITOR RIBOCICLIB, AND THE USE THEREOF IN THE TREATMENT/PREVENTION OF CANCER (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">The present disclosure pertains to a pharmaceutical combination comprising (a) an alpha-isoform specific P13K inhibitor, (b) a cyclin dependent kinase 4/6 (CDK4/6) inhibitor, and (c) an antimetabolite antineoplastic agent; combined preparations and pharmaceutical compositions thereof; the uses of such a combination in the treatment or prevention of cancer; and methods of treating or preventing cancer in a subject comprising administering a therapeutically effective amount of such combination.</p>
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Indolyl-Pyridone Derivatives Having Checkpoint Kinase 1 Inhibitory Activity (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">A method of treating a mammal suffering from a cancer responsive to inhibition of protein kinase activity, by administering to the mammal an amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, effective to inhibit protein kinase activity, wherein the compound of formula (I) is:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="52.41mm" wi="69.85mm" file="US20180244652A1-20180830-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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POLYMORPHIC FORMS AND CO-CRYSTALS OF A C-MET INHIBITOR (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">Provided herein are novel polymorphic forms and co-crystals of a compound useful in the treatment, prevention, or amelioration of cancer. In particular, the invention provides polymorphs and co-crystals of 6-{(1R)-1-[8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl}-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one, which is an inhibitor of c-Met.</p>
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TARGETED DELIVERY SYSTEM AND METHODS OF USE THEREFOR (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">Disclosed are peptides and peptidomimetics that in some embodiments include the amino acid sequence KRGARST or (SEQ ID NO: 1), AKRGARSTA or (SEQ ID NO: 2), or CKRGARSTC (SEQ ID NO: 3). Also disclosed are conjugates and compositions that onclude the peptides and/or peptidomimetics, methods for directing a moiety to tumor lymphatic vasculature, methods for imaging tumor lymphatic vasculature, methods for reducing or inhibiting tumor metastasis, methods for reducing the number of tumor lymphatic vessels, methods for treating cancer, methods for treating a disease or disorder associated with a gC1q/p32 receptor biological activity, methods for detecting the presence of a gC1q/p32 receptor, methods for detecting interactions between gC1q/p32 receptors and the presently disclosed conjugates and compositions, methods for delivering the presently disclosed conjugates and compositions to gC1q/p32 receptors, methods for assessing gC1q/p32 receptor levels in cells, methods for identifying subjects having diseases associated with gC1q/p32 receptor biological activities, and methods for screening for compounds that interact with gC1q/p32 receptors.</p>
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COMBINATION THERAPY FOR TREATMENT OF DISEASE (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">The present invention provides methods comprising combination therapy for modulating immune responses, for inhibiting tumor growth, and/or for treating cancer. In particular, the present invention provides Wnt pathway inhibitors in combination with immunotherapeutic agents for the treatment of cancer and other diseases.</p>
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HISTONE ACETYLTRANSFERASE MODULATORS AND USES THEREOF (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">The invention provides compounds and compositions comprising compounds that modulate histone acyl transferase (HAT). The invention further provides methods for treating neurodegenerative disorders, conditions associated with accumulated amyloid-beta peptide deposits, Tau protein levels and/or accumulations of alpha-synuclein as well as cancer by administering a compound hat modulates HAT to a subject.</p>
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Compounds And Compositions For The Treatment Of Cancer (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">Disclosed are compounds, such as pyridazinones, that can be, inter alia, used for treating cancer.</p>
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INHIBITION OF OLIG2 ACTIVITY (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of Olig2. Also described herein are methods of using such Olig2 inhibitors, alone and in combination with other compounds, for treating cancer and other diseases. In particular the Olig2 inhibitors may be used to treat glioblastoma.</p>
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CYCLOPROPYLDERIVATIVES AND THEIR USE AS KINASE INHIBITORS (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">The invention generally relates to cyclic compounds and, more particularly, to a compound represented by Structural Formula I: or a pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the multicyclic compounds. The invention also relates to a method for treating a disease or disorder selected from cancer (e.g., lymphoma, such as mantle cell lymphoma), a neurodegenerative disease, an inflammatory diseases or an immune system disease (e.g., a T-Cell mediated autoimmune disease) in a subject in need thereof. The method comprises administering to a subject in need thereof a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, or a composition comprising a compound of the invention, or a pharmaceutically acceptable salt thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.10mm" wi="62.06mm" file="US20180244660A1-20180830-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PROCESS FOR THE SYNTHESIS OF AN INDOLEAMINE 2,3-DIOXYGENASE INHIBITOR (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">The present application is directed to processes and intermediates for making 4-({2-[(aminosulfonyl)amino]ethyl}amino)-N-(3-bromo-4-fluorophenyl)-N′-hydroxy-1,2,5-oxadiazole-3-carboximidamide, which is an inhibitor of indoleamine 2,3-dioxygenase, useful in the treatment of cancer and other disorders.</p>
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PYRAZOL-3-ONES THAT ACTIVATE PRO-APOPTOTIC BAX (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">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).</p>
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PYRIDO-AZAHETERECYDIC COMPOUND AND PREPARATION METHOD AND USE THEREOF (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">The present invention discloses a pyrido-azacyclic compound represented by formula I, an isomer thereof, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, a preparation process thereof and a composition comprising the compound, and a use thereof as a multi-target protein kinase inhibitor in the preparation of a medicament for the treatment of diseases that are associated with protein kinase, especially c-Met, such as cancer and the like. The compound represented by formula I has potent inhibitory activity on tumor cells with overexpression of c-Met kinase, can effectively target c-Met-mediated signaling pathway, and can be used in the treatment of diseases such as cancer and the like that is caused by the overexpression of c-Met kinase.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="40.64mm" wi="69.93mm" file="US20180244667A1-20180830-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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BICYCLIC HETEROCYCLES AS FGFR4 INHIBITORS (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to bicyclic heterocycles, and pharmaceutical compositions of the same, that are inhibitors of the FGFR4 enzyme and are useful in the treatment of FGFR4-associated diseases such as cancer.</p>
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LRRK2 INHIBITORS AND METHODS OF MAKING AND USING THE SAME (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">Compounds having the formula I, II, or III:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="101.01mm" wi="62.23mm" file="US20180244676A1-20180830-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">are provided. Compounds of the present disclosure are useful for the treatment of neurodegenerative diseases, such as Parkinson's Disease.</p>
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CONDENSED TRICYCLIC COMPOUNDS AS PROTEIN KINASE INHIBITORS (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">There is provided compounds of formula I,</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.51mm" wi="69.85mm" file="US20180244687A1-20180830-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3 </sup>R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>7a </sup>and R<sup>7b </sup>have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. CDK8 and/or Haspin kinase) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.</p>
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Inhibitors of Tryptophan Dioxygenases (IDO1 and TDO) And Their Use In Therapy (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">Pharmaceutical compositions comprising 3-aminoisoxazolopyridine compounds of the Formula I having IDO1 and/or TDO inhibitory activity are described, where W is CR1, N or N-oxide; X is CR2, N or N-oxide; Y is CR3, N or N-oxide; Z is CR4, N or N-oxide; and at least one of W, X, Y, and Z is N or N-oxide; and R9 and R10 are as defined. Also described are methods of using such compounds in the treatment of various conditions, such as cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.81mm" wi="69.85mm" file="US20180244692A1-20180830-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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SIALYLTRANSFERASE INHIBITORS AND USES THEREOF (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">Disclosed herein are novel sialyltransferase inhibitors, and compositions and methods for treating diseases and/or conditions associated with the activation of sialyltransferase, such as a cancer, an immune disease or an inflammatory disease.</p>
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Anti-GITR Antibodies and Methods of Use Thereof (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">The present disclosure provides antibodies that specifically bind to human glucocorticoid-induced TNFR family related receptor (GITR) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human GITR and modulate GITR activity, e.g., enhance, activate or induce GITR activity, utilizing such antibodies. The present disclosure also provides methods for treating disorders, such as cancer and infectious diseases, by administering an antibody that specifically binds to human GITR and modulates GITR activity e.g., enhances, activates or induces GITR activity.</p>
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SYSTEMS AND METHODS FOR TARGETED CANCER THERAPIES (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">Systems and methods for producing liposomes, including control liposomes and various targeted liposomes. Systems and methods for treating conditions, such as, but not limited to various cancers, using targeted liposomes produced according to various methods disclosed herein. For example, estrone-conjugated liposomes may be used deliver chemotherapeutic agent(s) to breast cancer tissues for the treatment of breast cancer. Systems and methods for actuating liposomes using ultrasound. For example, systems and methods for actuating estrone-conjugated liposomes accumulated in breast cancer tissues for the treatment of breast cancer.</p>
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FUNCTIONALIZED NANOPARTICLES AND METHODS OF USE THEREOF (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">Certain embodiments of the present invention provide functionalized nanoparticles and methods of use thereof. Certain embodiments provide nanoparticles functionalized with streptokinase. Certain embodiments of the present invention provide methods for treating a pathological fibrin associated disorder (e.g., cancer) in an animal.</p>
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IMMUNOASSAY OF S-ADENOSYLMETHIONINE IN PERSONALIZED MEDICINE AND HEALTH OR CANCER EVALUATION (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">The invention provides a method of detecting the presence or absence of a disease in a patient wherein said disease is accompanied by deficient levels of S-adenosylmethionine comprising: identifying a patient that is suspected of having said disease or is at risk of having said disease; obtaining a biological sample from said patient; determining the level of S-adenosylmethionine in said biological sample using an antibody derived from a hapten analog of S-adenosylmethionine; and correlating the level of S-adenosylmethionine in said biological sample with the presence, absence, or severity of said disease. The invention also provides methods for measuring SAH which is used to determine the methylation index (ratio of SAM/SAH) in biological fluids which is indicative of the health status of an individual. Additionally, the invention includes test strips which are useful for determining S-adenosylmethionine and S-adenosylhomocysteine.</p>
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Biomarkers of Breast and Lung Cancer (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">Provided herein are methods of detecting lipids in humans suspected of having cancer, in particular detecting lipids in samples from a human suspected of having breast or lung cancer.</p>
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ISOTOPIC METHODS FOR MEASUREMENT OF TRYPTOPHAN AND METABOLITES THEREOF (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">Tryptophan degradation is a key metabolic pathway controlling immune reactions and evidence suggests that during cancer progression generation of tryptophan metabolites may be fundamental for immune escape promoting the malignant phenotype of cancer cells in an autocrine fashion. The present invention relates to methods of measuring mass tag labelled tryptophan and metabolites thereof and methods using the labelled molecules for monitoring in a subject the effectiveness of a treatment and of disease recurrence after treatment, for stratifying patients and for diagnosing suppression of an immune response in a subject.</p>
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MESOSCALE NANOPARTICLES FOR SELECTIVE TARGETING TO THE KIDNEY AND METHODS OF THEIR THERAPEUTIC USE (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">A drug carrier nanoparticle has been synthesized that can specifically target the proximal tubules of the kidneys. The nanoparticles accumulate in the kidneys to a greater extent than other organs (e.g., up to 3 or more times greater in the kidney than any other organ). They can encapsulate many classes of drug molecules. The nanoparticles are biodegradable and release the drug as they degrade. The particles can sustainably release a drug within the kidneys for up to two months. The nanoparticles are useful for the treatment of diseases that affect the proximal tubules, such as heart failure, liver cirrhosis, hypertension, and renal failure; the study of relative blood flow to the renal cortex and medulla; and delivery of agents to treat gout.</p>
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2,4,6-TRIALKOXYSTRYL ARYL SULFONES, SULFONAMIDES AND CARBOXAMIDES, AND METHODS OF PREPARATION AND USE (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">Compounds according to Formula I are provided:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.56mm" wi="69.85mm" file="US20180243239A1-20180830-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and salts thereof, wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>13</sup>, A, X and Y are as defined herein. Methods for preparing compounds of Formula I are also provided, as well as methods of treating cellular proliferative disorders, such as cancer, using compounds of Formula I.</p>
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TGF BETA RECEPTOR ANTAGONISTS (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">The invention relates generally to compounds that modulate the activity of TGFBETA R-1 and TGFBETA R-2, pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.</p>
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COMPOSITIONS AND METHODS FOR THE PRODUCTION OF PYRIMIDINE AND PYRIDINE COMPOUNDS WITH BTK INHIBITORY ACTIVITY (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">The present invention provides novel pyrimidine and pyridine compounds according to Formula (I), Formula (II), Formula (III), Formula (IV) and Formula (V) their manufacture and use for the treatment of hyperproliferative diseases including, but not limited to, cancer, lupus, allergic disorders, Sjogren's disease and rheumatoid arthritis. In preferred embodiments, the present invention describes irreversible kinase inhibitors including, but not limited to, inhibitors of Bruton's tyrosine kinase.</p>
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MODULATION OF TUMOR IMMUNITY BY PROTEIN-MEDIATED 02 DELIVERY (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">The invention provides methods to modulate hypoxia-mediated tumor immunity by administration of an O<sub>2 </sub>carrier polypeptide (e.g., an H-NOX protein). The methods of the invention target both hypoxia inducible factor 1 alpha (HIF-1α) pathways and non-HIF-1α pathways of tumor immunity. Such methods are useful in the treatment of a wide variety of cancers and may be used alone or in combination with other anti-cancer therapies.</p>
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BIOMARKER PANEL FOR THE DETECTION OF CANCER (Fri, 31 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to panels of methylation and mi RNA marker as well as their use in the prognosing, diagnosing and/or treatment of cancer, means for detecting said marker, kits comprising said means, and devices for analysing the marker panel.</p>
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DIHYDROPYRIDOPHTHALAZINONE COMPOUNDS AS INHIBITORS OF POLY (ADP-RIBOSE) POLYMERASE (PARP) FOR TREATMENT OF DISEASES AND METHOD OF USE THEREOF (Fri, 31 Aug 2018)
The present invention provides novel dihydropyridophthalazinone compounds of Formula (I) as PARP inhibitors, and their pharmaceutically acceptable salts, solvates, hydrates, prodrugs and metabolites thereof, the preparation thereof, and the use of such compounds to treat DNA repair dysregulation diseases and conditions such as cancer. The present provides therapeutic applications for the treatment of stroke, myocardial infarction, neurodegenerative diseases, ovarian cancer, breast cancer, prostate cancer, lung cancer, colorectal cancer, and melanoma.
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THERAPEUTIC DENDRIMERS (Fri, 31 Aug 2018)
Disclosed are dendrimers of formula (I): and pharmaceutically acceptable salts thereof. Also disclosed are pharmaceutical compositions comprising the dendrimer of formula (I) and methods of using the same for treating cancer.
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USE OF BIOMARKERS IN IDENTIFYING CANCER PATIENTS THAT WILL BE RESPONSIVE TO TREATMENT WITH A PRMT5 INHIBITOR (Fri, 31 Aug 2018)
The present invention concerns a method of identifying a patient that is likely to be responsive to treatment with a protein arginine N-methyltransferase 5 (PRMT5) inhibitor comprising: evaluating a biological sample from the patient for the presence of a spliceosome alteration, wherein the presence of any said alteration indicates a higher likelihood for said patient to be responsive to treatment with said PRMT5 inhibitor than in the absence of any said mutation or alteration.
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NOVEL AROMATIC COMPOUNDS (Fri, 31 Aug 2018)
The present invention comprises novel aromatic molecules, which can be used in the treatment of pathological conditions, such as cancer, skin diseases, muscle disorders, and immune system-related disorders such as disorders of the hematopoietic system including the hematologic system in human and veterinary medicine.
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5-(PYRIMIDIN-4-YL)-2-(PYRROLIDIN-1-YL)NICOTINONITRILE COMPOUNDS AS IKKE, TBK1 AND/OR SIK2 KINASES INHIBITORS (Fri, 31 Aug 2018)
The invention provides compounds of formula (I) wherein R is −CH3 or −CH2CH3 and pharmaceutically acceptable salts thereof. The compounds of formula (I) are useful in the treatment of diseases or disorders mediated by IKKE, TBK1 and/or SIK2 mechanisms in a subject, for example cancer and inflammatory and tissue repair disorders. The invention also provides uses of the compounds of formula (I) and compositions containing them. (Formula (I))
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HETEROCYCLIC AMIDES AS KINASE INHIBITORS (Fri, 31 Aug 2018)
Disclosed is a combination of a RIP1 kinase inhibitor compound and at least one other therapeutically active agent for use in the treatment of a RIP1 kinase mediated disease or disorder; particularly disclosed is a combination of a RIP1 kinase inhibitor compound and at least one other therapeutically active agent, wherein the at least one other therapeutically active agent is an immuno-modulator, for use in the treatment of cancer.
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COMPOUNDS AND METHODS FOR INHIBITING EMT PATHWAYS TO TREAT CANCER, ORGAN FIBROSIS AND METABOLIC DISORDERS (Fri, 31 Aug 2018)
A compound, or a pharmaceutically acceptable salt or isomer thereof, of Formula I: wherein R is hydrogen, alkyl, substituted alkyl, alkenyl, or substituted alkenyl; R1 is hydrogen, alkoxy, or substituted alkoxy; R2 is hydrogen, alkyl, or substituted alkyl; and R3 is hydrogen, alkyl, or substituted alkyl.
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CHEMOKINE CXCR4 RECEPTOR MODULATORS AND USES RELATED THERETO (Fri, 31 Aug 2018)
The disclosure relates to chemokine CXCR4 receptor modulators and uses related thereto. The receptor modulators can be formulated to form pharmaceutical compositions comprising the disclosed compounds or pharmaceutically acceptable salts or prodrugs thereof. The compositions may be used for managing CXCR4 related conditions, typically prevention or treatment of viral infections abnormal cellular proliferation, retinal degeneration, inflammatory diseases, or as an immunostimulant or immunosuppressant or for managing cancer and may be administered with another active ingredient such as an antiviral agent or chemotherapeutic agent.
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NOVEL SMALL MOLECULE ANTICANCER AGENTS (Fri, 31 Aug 2018)
The invention relates to methods of treating cell proliferative disorders. The invention further relates to pharmaceutical compositions for treating cell proliferative disorders, especially cancer.
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CYCLIC DINUCLEOTIDES AS AGONISTS OF STIMULATOR OF INTERFERON GENE DEPENDENT SIGNALLING (Fri, 31 Aug 2018)
Disclosed herein are new cyclic dinucleotide compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of modulation of immune response to disease, and induce Stimulator of Interferon Genes (STING) dependent type I interferon production and co-regulated genes in a human or animal subject are also provided for the treatment diseases such as cancer, particularly metastatic solid tumors and lymphomas, inflammation, allergic and autoimmune disease, infectious disease, and for use as anti-viral agents and vaccine adjuvants.
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TREATMENT OF EGFR-DRIVEN CANCER WITH FEWER SIDE EFFECTS (Fri, 31 Aug 2018)
The present invention provides methods for treating a EGFR-mutant cancer in a patient by administering a selective CDK4/6 inhibitor described herein in combination or alternation with an EGFR-TKI to delay or reverse acquired resistance to previously administered EGFR-TKIs. In addition, methods for treating a EGFR-mutant cancer in a patient by administering a selective CDK4/6 inhibitor described herein in combination or alternation with an EGFR-TKI are provided wherein an intrinsically EGFR-TKI resistant EGFR-mutant cancer is sensitized to the effects of the EGFR-TKI.
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METHODS OF TREATMENT FOR CANCER, STEROL HOMEOSTASIS, AND NEUROLOGICAL DISEASES (Fri, 31 Aug 2018)
The present disclosure provides methods of treating cancer, sterol homeostasis diseases, and neurological diseases using compounds which modulate the activity of sigma receptors. In particular, the present disclosure provides method s of modulating the sigma 2 receptor for use in treating one or more diseases associated with that sigma receptor.
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ASSAY FOR DETECTION OF EARLY STAGE PANCREATIC CANCER (Fri, 31 Aug 2018)
Provided herein are methods of detecting pancreatic cancer, particularly early stage pancreatic cancer, comprising measuring the expression of the biomarker panel TNC-FN III-C, TFPI, and CA19-9. The expression may be determined by an ELISA, such as a multiplex ELISA. Further provided herein are methods of treating subjects identified to have pancreatic cancer.
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TRICYCLIC COMPOUNDS AS INHIBITORS OF IMMUNOSUPPRESSION MEDIATED BY TRYPTOPHAN METABOLIZATION (Thu, 30 Aug 2018)
Presently provided are inhibitors of IDO and TDO and pharmaceutical compositions thereof, useful for modulating an activity of indoleamine 2,3-dioxygenase and tryptophan 2,3 dioxygenase; treating immunosuppression; treating a medical conditions that benefit from the inhibition of tryptophan degradation; enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent; treating tumor-specific immunosuppression associates with cancer; and treating immunosupression associated with an infectious disease.
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CYCLIC PURINE DINUCLEOTIDES AS MODULATORS OF STING (Thu, 30 Aug 2018)
A compound of Formula (VI) wherein R 58 and R 59 are independently selected from: H, CH 2 OC(O)R 57 , CH 2 OCO 2 R 57 , CH 2 CH 2 SC(O)R 57 , and CH 2 CH 2 SSCH 2 R 57 ; provided that at least one of R 58 and R 59 is not H; R 56 is F; X 51 O; X 52 is O. Pharmaceutically acceptable salts and tautomers thereof, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, in the treatment of diseases in which modulation of STING (Stimulator of Interferon Genes) is beneficial, for example inflammation, allergic and autoimmune diseases, infectious diseases, cancer, pre-cancerous syndromes and as vaccine adjuvants.
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HDAC inhibitors and therapeutic methods using the same (Wed, 29 Aug 2018)
<p id="p-0001" num="0000">Histone deacetylases inhibitors (HDACIs) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a peripheral neuropathy, a neurological disease, traumatic brain injury, stroke, hypertension, malaria, an autoimmune disease, autism, autism spectrum disorders, and inflammation, also are disclosed.</p>
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PLATELET MEMBRANE-COATED DRUG DELIVERY SYSTEM (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">Disclosed herein is a platelet membrane-coated nanovehicle having an inner core comprising a drug delivery matrix, and an outer shell platelet membrane coating the inner core. The inner core can be any drug delivery matrix capable of delivering a therapeutic agent to a cell. The outer shell platelet membrane can be a natural or synthetic membrane comprising platelet proteins capable of interacting with cancer cells. Also disclosed is a method for treating cancer in a subject that involves administering to the subject a platelet membrane-coated nanovehicle disclosed herein. Also disclosed is a method for treating vascular disease in a subject that involves administering to the subject a platelet membrane-coated nanovehicle disclosed herein.</p>
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BISPHENOL COMPOUNDS AND METHODS FOR THEIR USE (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">Compounds having a structure of Formula I: wherein G, a, Q, L<sup>2</sup>, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5 </sup>and R<sup>6 </sup>are as defined herein 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> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="43.01mm" wi="64.01mm" file="US20180235925A1-20180823-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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METHOD FOR USE OF HOMOPIPERAZINIUM COMPOUNDS IN THE TREATMENT OF CANCER (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">A method for treating cancer including administering to a patient in need thereof an effective amount of a compound having the formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.63mm" wi="25.23mm" file="US20180235978A1-20180823-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sub>1</sub>, R<sub>2 </sub>, Ya, Xa, and J<sup>−</sup> are as defined herein, and may be where R1 and R2 are independently selected from methyl, ethyl, n-propyl, or i-propyl; Xa is N or CH; Ya is hydrogen or independently selected from halogen, cyano, hydroxyl, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, heteroaryl of 6 members and aryl; n is 1 or 2; wherein J<sup>−</sup> is fluoride, chloride, bromide, iodide, acetate, sulfate or sulfonate such as tosylate, mesylate, besylate.</p>
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MANNOSE DERIVATIVES USEFUL FOR TREATING PATHOLOGIES ASSOCIATED WITH ADHERENT E. COLI (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to mannose derivatives of formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.04mm" wi="69.85mm" file="US20180235991A1-20180823-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">R<sub>1 </sub>represents H, CO—(C<sub>1</sub>-C<sub>6</sub>)-alkyl or CO-alkylaryl,</li> <li id="ul0002-0002" num="0000">Y represents a single bond, CH<sub>2</sub>, O, NR<sub>3</sub>, S,</li> <li id="ul0002-0003" num="0000">A represents O, NH or S,</li> <li id="ul0002-0004" num="0000">X represents H and X′ represents OH or X and X′ taken together with the carbon atom bearing them form a CO group,</li> <li id="ul0002-0005" num="0000">R<sub>2 </sub>represents H, a linear or branched (C<sub>1</sub>-C<sub>6</sub>)-alkyl or CF<sub>3</sub>,</li> <li id="ul0002-0006" num="0000">R<sub>3 </sub>represents H, a C<sub>1</sub>-C<sub>6 </sub>alkyl, a CO—(C<sub>1</sub>-C<sub>6</sub>)-alkyl, CF<sub>3 </sub>or COCF<sub>3</sub>, and</li> <li id="ul0002-0007" num="0000">R is as described in claim <b>1. </b></li> </ul> </li> </ul> </p> <p id="p-0004" num="0000">The mannose derivatives of formulae (I) are useful for treating pathologies associated with the presence of adherent <i>Escherichia coli </i>(AEC), in particular inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis; a urinary tract infection, in particular painful bladder syndrome and cystitis, more particularly interstitial cystitis; irritable bowel syndrome; metabolic diseases such as metabolic obesity, diabetes, hypercholesterolemia; autoimmune inflammatory diseases; and colorectal cancer, in particular colon cancer.</p>
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MELAMPOMAGNOLIDE B DIMERS (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The present disclosure provides dimers of melampomagnolide B (MMB), including carbamate, carbonate, succinic amide, ester and carboxamide dimers of MMB. These derivatives are useful for treating cancer in humans, in particular in treating leukemia, including acute myelogenous leukemia (AML).</p>
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ASSAYS FOR DETECTING T CELL IMMUNE SUBSETS AND METHODS OF USE THEREOF (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The present disclosure provides methods for measuring the number of CD4+ OX40+ Foxp3+ lymphocytes in a sample containing cancer cells and lymphocytes obtained from a subject by labeling lymphocytes that show CD4 expression in the sample, then labeling lymphocytes that show OX40 expression in the sample, then labeling lymphocytes that show Foxp3 expression in the sample, then measuring the number of CD4+ OX40+ Foxp3+ lymphocytes in the sample. Further provided are methods for determining the prognosis of a subject, predicting responsiveness of a subject having cancer to an OX40 agonist treatment, and methods for treating or delaying progression of cancer based on the number of CD4+ OX40+ Foxp3+ lymphocytes in a sample.</p>
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PD-L2 BIOMARKERS PREDICTIVE OF PD-1 PATHWAY INHIBITOR RESPONSES IN ESOPHAGOGASTRIC CANCERS (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The present invention is based on the identification of novel biomarkers predictive of responsiveness of esophagogastric cancers to inhibitors of the PD-1 pathway.</p>
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METHODS FOR TREATING HEMATOLOGICAL CANCER AND THE USE OF BIOMARKERS AS A PREDICTOR FOR RESPONSIVENESS TO TREATMENT COMPOUNDS (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">A method for predicting the responsiveness of a patient having a hematological cancer to a treatment compound, comprising obtaining a biological sample from the patient having the hematological cancer; determining the expression level of one, two, three, four, five, or more genes; and comparing the expression level of the one, two, three, four, five, or more genes in the biological sample with a reference expression level of the same genes, wherein the treatment compound is 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione (lenalidomide), 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione (Compound A), or a stereoisomer, pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or a polymorph thereof.</p>
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NOVEL GLUCOSE DERIVATIVE, AND CELL IMAGING METHOD AND IMAGING AGENT USING SAID DERIVATIVE (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">Provided is a glucose derivative, which is taken into cells via a membrane sugar transport system and is represented by formula (1). Also provided are an imaging agent and an imaging method for a cell or intracellular molecule using said glucose derivative. Further provided is a method for detecting cancer cells with good accuracy using said glucose derivative and an imaging agent to be used in said method. More specifically provided are D-glucose derivatives and L-glucose derivatives in which glucose is bound to the 7-position of a fluorescent molecular group with a coumarin backbone or a quinolone backbone. Also provided are a cell imaging agent and imaging method using the derivative. A cancer cell imaging agent and imaging method using the L-glucose derivative is also provided. G is a group selected from formulas (G1)-(G4) below.</p>
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NOVEL CARBOCYCLIC COMPOUNDS AS ROR GAMMA MODULATORS (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The present disclosure is directed to novel carbocyclic compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>a</sup>, R<sup>b</sup>, n, m 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.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.72mm" wi="76.03mm" file="US20180237382A1-20180823-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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AGONISTS OF PROTEIN TYROSINE PHOSPHATASE SHP-1 (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">Some novel compounds are provided in this disclosure. These novel compounds have potential SHP-1 agonist activity for being used in treating cancer.</p>
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Chemical Compounds (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The invention is directed to substituted pyrrolidinone and imidazolidinone derivatives. Specifically, the invention is directed 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="24.81mm" wi="58.93mm" file="US20180237441A1-20180823-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>7</sup>, X and Y are as defined herein.</p> <p id="p-0004" num="0000">The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases/injuries associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson's disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.</p>
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Chemical Compounds (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The present disclosure concerns compounds of Formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.62mm" wi="69.85mm" file="US20180237443A1-20180823-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically-acceptable salts thereof, wherein R<sup>1</sup>, R<sup>2 </sup>and R<sup>3 </sup>have any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cancer.</p>
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INHIBITORS OF ERK AND METHODS OF USE (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The present invention provides chemical entities or compounds and pharmaceutical compositions thereof that are capable of modulating certain protein kinases such as ERK (MAPK). Also provided are methods of using such compounds or compositions, and methods of using these compositions to modulate the activities of one or more of these kinases, especially for therapeutic applications such as the treatment disorders such as cancer.</p>
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INSULIN-LIKE GROWTH FACTOR 2 (IGF2) BINDING AGENTS (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">This invention relates to mutant polypeptides comprising the IGF2 binding domain of the Insulin-like Growth Factor 2 Receptor (IGF2R) with residue P1597 is substituted for a different residue, for example H or K. Other residues which may be mutated include S1543, E1544, K1545, G1546, L1547, Q1569, S1602, G1603 and/or K1631. These IGF2 binding domains display dramatically increased binding affinity for IGF2 compared to both the wild-type and previously identified mutants and may be useful for example in cancer therapy.</p>
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ANTIBODIES AGAINST OX40 AND USES THEREOF (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">Provided herein are antibodies, or antigen binding portions thereof, that bind to OX40. Also provided are uses of these proteins in therapeutic applications, such as in the treatment of cancer. Further provided are cells that produce the antibodies, polynucleotides encoding the heavy and/or light chain variable region of the antibodies, and vectors comprising the polynucleotides encoding the heavy and/or light chain variable region of the antibodies.</p>
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UNIMOLECULAR NANOPARTICLES FOR EFFICIENT DELIVERY OF THERAPEUTIC CATIONIC PEPTIDES (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">Provided herein are peptides comprising an amino acid sequence having at least about 85% sequence identity to RYRPRAPIIAVT (SEQ ID NO: 1). These cationic peptides inhibit PKM2 methylation and may be used in the treatment of breast cancer and other diseases or conditions in which PKM2 is overexpressed. Such PKM2 peptides may be delivered to cancer cells using pH sensitive unimolecular nanoparticles comprising anionic polymers.</p>
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CRYSTALLINE FORM OF LORLATINIB FREE BASE (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">This invention relates to acrystalline form of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-5-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h] [2,5,11]benzoxadiazacyclo-tetradecine-3-carbonitrile (lorlatinib) free base (Form 7). This invention also relates to pharmaceutical compositions comprising Form 7, and to methods of using Form 7 and such compositions in the treatment of abnormal cell growth, such as cancer, in a mammal.</p>
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(S,E)-3-(6-AMINOPYRIDIN-3-YL)-N-((5-(4-(3-FLUORO-3-METHYLPYRROLIDINE-1-CARBONYL)PHENYL)-7-(4-FLUOROPHENYL)BENZOFURAN-2-YL)METHYL)ACRYLAMIDE FOR THE TREATMENT OF CANCER (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The invention generally relates to substituted benzofuranyl compounds and, more particularly, to a compound represented by Structural Formula 1a: (I) or a pharmaceutically acceptable salt thereof. The invention also includes the synthesis and use of the compound of Structural Formula 1a, or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment of diseases or disorder selected from cancer (e.g., lymphoma, such as mantle cell lymphoma), a neurodegenerative disease, an inflammatory diseases or an immune system disease (e.g., a T-Cell mediated autoimmune disease) in a subject in need thereof. The method comprises administering to a subject in need thereof a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof, or a composition comprising a compound of the invention, or a pharmaceutically acceptable salt thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.95mm" wi="75.44mm" file="US20180235948A1-20180823-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Substituted 1-Arylalkyl-4-Acylaminopiperidine Compounds and Methods of Producing and Using the Same (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The present invention provides using a substituted 1-arylalkyl-4-acylaminopiperidine compound of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="14.48mm" wi="59.61mm" file="US20180235949A1-20180823-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">to treat various clinical conditions including, but not limited to, hemorrhagic shock, nicotine withdrawal symptoms, gastrointestinal side effects of opioids, cancer therapy, epithelial wounds, herpes zoster infection, or opioid-induced pruritus. In compound of Formula I, R<sup>1 </sup>is C<sub>1-10 </sub>alkyl, C<sub>1-10 </sub>haloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; R<sup>2 </sup>is C<sub>1-6 </sub>alkylene; Y is optionally substituted aryl, optionally substituted heteroaryl, or a moiety of the formula —C(═O)—X<sup>1</sup>, wherein X<sup>1 </sup>is —OR<sup>3 </sup>or —NR<sup>4</sup>R<sup>5</sup>, where each of R<sup>3</sup>, R<sup>4 </sup>and R<sup>5 </sup>is H or C<sub>1-10 </sub>alkyl.</p>
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COMPOSITIONS AND METHODS FOR CANCER EXPRESSING PDE3A OR SLFN12 (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The present invention features improved methods of identifying patients having cancer (e.g., melanoma, adenocarcinoma, lung, cervical, liver or breast cancer) using biomarkers (e.g., PDE3A, SLFN12) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention (e.g., DNMDP, zardaverine, and anagrelide).</p>
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NOVEL POLYGODIAL ANALOGS FOR THE TREATMENT OF CANCER AND OTHER PROLIFERATIVE DISEASES (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The present disclosure relates generally to derivatives of polygodial and methods of use thereof. In some aspects, the present disclosure relates to using polygodial derivatives to treat cancer or other hyperproliferative diseases.</p>
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SMALL MOLECULE INHIBITORS OF THE NUCLEAR TRANSLOCATION OF ANDROGEN RECEPTOR FOR THE TREATMENT OF CASTRATION-RESISTANT PROSTATE CANCER (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">A compound, or a pharmaceutically acceptable salt or ester thereof, according to formula I:</p> <p id="p-0002" num="0000"> <br/> <?in-line-formulae description="In-line Formulae" end="lead"?>R<sup>20</sup>—(Z)<sub>b</sub>—(Y)<sub>c</sub>—(R<sup>21</sup>)<sub>a</sub>—(X)<sub>d</sub>—R<sup>22</sup>—R<sup>23 </sup><?in-line-formulae description="In-line Formulae" end="tail"?> </p> <p id="p-0003" num="0000">wherein R<sup>20 </sup>is aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a thio-containing group, or a seleno-containing group; Z is alkanediyl, substituted alkanediyl, cycloalkanediyl, or substituted cycloalkanediyl; Y is S, O, S(═O), —S(═O)(═O)—, or NR<sup>10</sup>, wherein R<sup>10 </sup>is H or alkyl; R<sup>21 </sup>is alkanediyl, substituted alkanediyl, cycloalkanediyl, substituted cycloalkanediyl alkadienyl, substituted alkadienyl, alkatrienyl, substituted alkatrienyl; X is —C(═O)—, —S(═O)(═O)—, or —N(H)C(═O)—; R<sup>22 </sup>includes at least one divalent amino radical; R<sup>23 </sup>is aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a thio-containing group, or a seleno-containing group; a, b, c, and d independently are 0 or 1.</p>
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PHENYLSULFONAMIDO-BENZOFURAN DERIVATIVES AND USES THEREOF IN THE TREATMENT OF PROLIFERATIVE DISEASES (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">Described herein are phenylsulfonamido-benzofuran derivatives, and pharmaceutically acceptable salts thereof. Also provided are pharmaceutical compositions, methods, uses, and kits involving compounds of Formulae (I), (II), (III), (IV), (V), or (VI) for treating and/or preventing proliferative diseases (e.g. cancers, inflammatory diseases, and autoimmune diseases) in a subject. The compounds and pharmaceutical compositions as described herein inhibit at least one protein of the BCL-2 family in a biological sample or subject to treat and/or prevent a proliferative disease. In certain embodiments, compounds described herein are selective inhibitors of MCL-1, a BCL-2 family member protein.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="234.70mm" wi="59.86mm" file="US20180237406A1-20180823-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="46.31mm" wi="58.93mm" file="US20180237406A1-20180823-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PHENYLSULFONAMIDO-BENZOFURAN DERIVATIVES AND USES THEREOF IN THE TREATMENT OF PROLIFERATIVE DISEASES (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">Described herein are phenylsulfonamido-benzofuran derivatives, and pharmaceutically acceptable salts thereof. Also provided are pharmaceutical compositions, methods, uses, and kits involving compounds of Formulae (I), (II), (III), (IV), (V), or (VI) for treating and/or preventing proliferative diseases (e.g. cancers, inflammatory diseases, and autoimmune diseases) in a subject. The compounds and pharmaceutical compositions as described herein inhibit at least one protein of the BCL-2 family in a biological sample or subject to treat and/or prevent a proliferative disease. In certain embodiments, compounds described herein are selective inhibitors of MCL-1, a BCL-2 family member protein.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="243.16mm" wi="59.86mm" file="US20180237407A1-20180823-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="46.40mm" wi="58.93mm" file="US20180237407A1-20180823-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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FGFR3 ANTAGONISTS (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The invention pertains to novel FG-FR3antagonists of general formula (I), The compounds are useful for the treatments and prevention of achondroplasia and cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.85mm" wi="54.44mm" file="US20180237424A1-20180823-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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ALDOSE REDUCTASE INHIBITORS AND METHODS OF USE THEREOF (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The present disclosure relates to novel compounds and pharmaceutical compositions thereof, and methods for promoting healthy aging of skin, the treatment of skin disorders, the treatment of cardiovascular disorders, the treatment of renal disorders, the treatment of angiogenesis disorders, such as cancer, treatment of tissue damage, such as non-cardiac tissue damage, the treatment of evolving myocardial infarction, the treatment of ischemic injury, and the treatment of various other disorders, such as complications arising from diabetes with the compounds and compositions of the invention. Other disorders can include, but are not limited to, atherosclerosis, coronary artery disease, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, diabetic cardiomyopathy, infections of the skin, peripheral vascular disease, stroke, asthma, and the like.</p>
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HERCEPTIN® ADJUVANT THERAPY (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The present application describes adjuvant therapy of nonmetastatic breast cancer using HERCEPTIN®.</p>
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ANTIBODY DRUG CONJUGATES (ADC) THAT BIND TO CD37 PROTEINS (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">Antibody drug conjugates (ADC's) that bind to CD37 protein and variants thereof are described herein. CD37 exhibits a distinct and limited expression pattern in normal adult tissue(s), and is aberrantly expressed in the cancers listed in Table I. Consequently, the ADC's of the invention in some embodiments provide a therapeutic composition for the treatment of cancer.</p>
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PSMA-BINDING AGENTS AND USES THEREOF (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">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.</p>
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INDAZOLE-3-CARBOXAMIDES AND THEIR USE AS WNT/B-CATENIN SIGNALING PATHWAY INHIBITORS (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">Indazole-3-carboxamide compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an indazole-3-carboxamide compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis 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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INHIBITORS OF BETA-HYDROXYLASE FOR TREATMENT OF CANCER (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to compounds which modulate (e.g., inhibit) the activity of beta-hydrolase (e.g., ASPH), including novel 2-aryl-5-amino-3(2H)-furanone and 2-heteroaryl-5-amino-3(2H)-furanone compounds, pharmaceutical compositions thereof, methods for their synthesis, and methods of using these compounds to modulate the activity of ASPH in an a cell-free sample, a cell-based assay, and in a subject. Other aspects of the invention relate to use of the compounds disclosed herein to ameliorate or treat cell proliferation disorders.</p>
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NOVEL COMPOUNDS AS ROR GAMMA MODULATORS (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The present disclosure is directed to compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein ring A, ring B, L, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>a</sup>, R<sup>b</sup>, n, m, p and q are as defined herein, which are active as modulators of retinoid-related Sorphan receptor gamma t (RORγt). These compounds prevent, inhibit, or suppress the action of RORγt and are therefore useful in the treatment of RORγt mediated diseases, disorders, syndromes or conditions such as, e.g., pain, inflammation, COPD, asthma, rheumatoid arthritis, colitis, multiple sclerosis, psoriasis, neurodegenerative diseases and cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.09mm" wi="75.69mm" file="US20180237428A1-20180823-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPOSITIONS AND METHODS FOR TREATING NEOPLASIA, INFLAMMATORY DISEASE AND OTHER DISORDERS (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The invention features compositions and methods for treating or preventing a neoplasia. More specifically, the invention provides compositions and methods for disrupting the interaction of a BET family polypeptide comprising a bromodomain with chromatin (e.g., disrupting a bromodomain interaction with an acetyl-lysine modification present on a histone N-terminal tail).</p>
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COT MODULATORS AND METHODS OF USE THEREOF (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">The present disclosure relates generally to modulators of Cot (cancer Osaka thyroid) and methods of use and manufacture thereof.</p>
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Compounds for the Treatment of Cancer (Fri, 24 Aug 2018)
<p id="p-0001" num="0000">Provided herein are compounds useful for the treatment of cancer.</p>
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DEFINING RNA-SMALL MOLECULE AFFINITY LANDSCAPES ENABLES DESIGN OF A SMALL MOLECULAR INHIBITOR OF AN ONCOGENIC NON-CODING RNA (Fri, 24 Aug 2018)
RNA drug targets are pervasive in cells but methods to design small molecules that target them are sparse. Herein, we report a general approach to score the affinity and selectivity of RNA motif-small molecule interactions identified via selection. Named High Throughput Structure-Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif-small molecule binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a small molecule and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the small molecule, Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cluster, de-repressed serine/threonine protein kinase 4 protein (STK4), and triggered apoptosis. Profiling the cellular targets of Targapremir-18a via Chemical Cross Linking and isolation by Pull Down (Chem-CLIP), a covalent small molecule-RNA cellular profiling approach, and other studies showed specific binding of the compound to the miR-18a precursor, revealing broadly applicable factors that govern small molecule drugging of non-coding RNAs.
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ANALOGS OF VINCAMINE AND USES THEREOF (Fri, 24 Aug 2018)
The present disclosure provides compounds of any one of Formulae (I'), (I), (IA), (II'), (II), (IIA), (IIIA), (III"), (III'), (III), (IIIA), (IV), (V'), (V), (VI), (VII), (VIII'), (VIII), (ΙΧ'), (IX), and (X). The compounds described herein may be useful in treating and/or preventing a broad range of diseases (e.g., proliferative disease (e.g., cancers (e.g., non-small cell lung cancer, or glioma), inflammatory diseases, autoimmune diseases), CNS disorder (e.g., drug addiction), metabolic disorder (e.g., diabetes), or infectious disease (e.g., bacterial infection or parasitic infection (e.g., malaria))). Also provided in the present disclosure are pharmaceutical compositions, methods of synthesis of a compound described herein, kits, methods, and uses including or using a compound described herein.
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PIPERIDINE-SUBSTITUTED MNK INHIBITORS AND METHODS RELATED THERETO (Fri, 24 Aug 2018)
The present invention relates to compounds according to Formula (I): or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof wherein X1, X2, R1, R2, R3 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.
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PYRAZOLOPYRIDINE COMPOUNDS AND USES THEREOF (Fri, 24 Aug 2018)
Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting HPK1 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer.
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CALCIUM CHANNEL INHIBITORS (Fri, 24 Aug 2018)
The present disclosure describes carbamate analogs of mibefradil, as well as their compositions and methods of use. The compounds block the activity of one or more isoforms of voltage-gated calcium channels and are useful in the treatment of diseases including, e.g., cancer.
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SUBSTITUTED IMIDAZO-QUINOLINES AS NLRP3 MODULATORS (Fri, 24 Aug 2018)
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 an increase in NLRP3 signaling may correct a deficiency in innate immune activity (e.g., a condition, disease or disorder associated with an insufficient immune response) that 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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CYCLIC DI-NUCLEOTIDES COMPOUNDS FOR THE TREATMENT OF CANCER (Fri, 24 Aug 2018)
Provided herein are compounds useful for the treatment of cancer.
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CYCLIC DI-NUCLEOTIDES DERIVATIVE FOR THE TREATMENT OF CANCER (Fri, 24 Aug 2018)
Provided herein are compounds useful for the treatment of cancer.
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COMPOUNDS FOR TREATMENT OF CANCER AND EPIGENETICS (Fri, 24 Aug 2018)
The present invention relates to heterocyclic compounds having the general Formula (I) wherein W1, W2, W3, W4, W7, W8, R1, R2, R3, R4, X2, X3, X4, Z1, Z2, Z3, Q, n and m are as defined herein, or a pharmaceutically acceptable salt thereof, wherein the compound is useful for treating SMYD3- related cancer.
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CANNABINOID RECEPTOR MODULATORS (Thu, 23 Aug 2018)
The present invention relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB 2 receptor. The present invention further relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activities of both the CB 1 receptor and the CB 2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pain, for example bone and joint pain, muscle pain, dental pain, migraine and other headache pain, inflammatory pain, neuropathic pain, pain that occurs as an adverse effect of therapeutics and pain associated with osteoarthritis; hyperalgesia; allodynia; inflammatory hyperalgesia; neuropathic hyperalgesia; acute nociception; osteoporosis; multiple sclerosis-associated spasticity; autoimmune disorders; allergic reactions; CNS inflammation; atherosclerosis; undesired immune cell activity and inflammation; age-related macular degeneration; cough; leukemia; lymphoma; CNS tumors; prostate cancer; Alzheimer's disease; stroke-induced damage; dementia; amyotrophic lateral sclerosis, and Parkinson's disease.
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PHARMACEUTICAL COMPOSITION CONTAINING, AS ACTIVE INGREDIENT, 7-AZAINDOLIN-2-ONE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF (Thu, 23 Aug 2018)
The present invention relates to a 7-azaindolin-2-one derivative or a pharmaceutically acceptable salt thereof, and the 7-azaindolin-2-one derivative or the pharmaceutically acceptable salt thereof can be favorably used as a medicinal material for inhibiting cancer growth and cancer metastasis.
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HETEROCYCLIC INHIBITORS OF ERK AND METHODS OF USE (Thu, 23 Aug 2018)
The present invention provides compounds of formula (II-E) and pharmaceutical compositions thereof that are capable of modulating certain protein kinases such as ERK (MAPK). Also provided are methods of using such compounds or compositions, and methods of using these compositions to modulate the activities of one or more of these kinases, especially for therapeutic applications such as the treatment disorders such as cancer.
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PHARMACEUTICAL COMPOSITION FOR TREATING CANCER COMPRISING RNA OLIGONUCLEOTIDE (Thu, 23 Aug 2018)
The present disclosure provides a pharmaceutical composition for treating cancer comprising an RNA oligonucleotide having a particular sequence and structure. Specifically, when a cell line is treated with an RNA oligonucleotide having specific sequence and helical bend structure according to the present disclosure, the expression of ISG56 is increased and apoptosis of cancer cells is induced. Thus, a composition comprising the RNA oligonucleotide can be used as an anticancer agent.
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Isoxazole Carboxamides as Irreversible SMYD Inhibitors (Fri, 17 Aug 2018)
<p id="p-0001" num="0000">The present disclosure provides substituted isoxazole carboxamides having Formula (I), and the pharmaceutically acceptable salts and solvates thereof, wherein R<sup>1</sup>, R<sup>2a</sup>, R<sup>2b</sup>, R<sup>3a</sup>, R<sup>3b</sup>, X, n, and m are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.55mm" wi="62.23mm" file="US20180230110A1-20180816-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS (Fri, 17 Aug 2018)
<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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3-(1H-BENZO[D]IMIDAZOL-2-YL)-1H-PYRAZOLO[4,3-B]PYRIDINES AND THERAPEUTIC USES THEREOF (Fri, 17 Aug 2018)
<p id="p-0001" num="0000">4-Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of a 4-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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SALINOMYCIN DERIVATIVES AND THERAPEUTIC USES THEREOF (Fri, 17 Aug 2018)
<p id="p-0001" num="0000">The invention relates to salinomycin derivatives such as compounds having the structure of formula (I) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising a therapeutically effective amount of compounds of formula (I), and the use of compounds of formula (I) for treating or inhibiting progression of cancer. The cancer is selected from the group consisting of breast cancer, pancreatic cancer, and prostate cancer.</p>
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CHIMERIC COMPOUNDS TARGETING PROTEINS, COMPOSITIONS, METHODS, AND USES THEREOF (Fri, 17 Aug 2018)
<p id="p-0001" num="0000">The present invention provides chimeric compounds that modulate protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, TNF-alpha activity, CK1-alpha activity and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of protein-mediated diseases, disorders, and conditions, such as cytokine-mediated diseases, disorders, and conditions, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, organ transplant rejection, and cancer, are provided.</p>
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Compositions and Methods for Inhibiting Gene Expression of Hif2alpha (Fri, 17 Aug 2018)
<p id="p-0001" num="0000">RNA interference (RNAi) triggers and RNAi trigger conjugates for inhibiting the expression of Hif2α (EPAS1) gene are described. Pharmaceutical compositions comprising one or more Hif2α RNAi triggers optionally with one or more additional therapeutics are also described. Delivery of the described Hif2α RNAi triggers to tumor cells in vivo provides for inhibition of Hif2α gene expression and treatment of cancer.</p>
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1,4-DISUBSTITUTED IMIDAZOLE DERIVATIVE (Fri, 17 Aug 2018)
<p id="p-0001" num="0000">The present invention provides a 1,4-disubstituted imidazole derivative of formula (1′) wherein ring Q<sup>1 </sup>is optionally-substituted C<sub>6-10 </sub>aryl group, etc.; R<sup>1 </sup>and R<sup>2 </sup>are independently hydrogen atom, etc.; W<sup>1 </sup>is optionally-substituted C<sub>1-4 </sub>alkylene group; W<sup>2 </sup>is —NR<sup>3a</sup>C(O)— wherein R<sup>3a </sup>is hydrogen atom or C<sub>1-6</sub>alkyl group, etc.; ring Q<sup>2 </sup>is 5- to 10-membered heteroaryl group, etc.; W<sup>3 </sup>is optionally-substituted C<sub>1-4 </sub>alkylene group, etc.; n is 1, 2, 3, 4, or 5; R<sup>4 </sup>is independently halogen atom, optionally-substituted C<sub>1-6 </sub>alkyl group, etc.; R<sup>5 </sup>is hydroxy group, etc.; and a pharmacologically acceptable salt thereof, which have a potent inhibitory effect on the sphere-forming capacity of cancer cells and are useful as an orally-available anti-tumor agent.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.55mm" wi="69.85mm" file="US20180230085A1-20180816-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Ataxia Telengiectasia And Rad3-Related (ATR) Protein Kinase Inhibitors (Fri, 17 Aug 2018)
<p id="p-0001" num="0000">Macrocyclic compounds having the structure of Formula (A), or pharmaceutically acceptable salts thereof, are provided:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.60mm" wi="69.85mm" file="US20180230168A1-20180816-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and R<sup>5 </sup>are defined herein. Also provided are pharmaceutical compositions comprising the macrocyclic compound and methods for treating cancer in a patient comprising administering to the patient the macrocyclic compound.</p>
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Peptidomimetics for Treating HER2-Overexpressd Cancer (Fri, 17 Aug 2018)
<p id="p-0001" num="0000">Novel peptidomimetic compounds are disclosed, compounds that inhibit protein-protein interactions (PPI) of epidermal growth factor receptors (EGFR), also called human epidermal growth factor receptors (HERs), and that block signaling for cell growth in HER2-overexpressed cancers. The novel peptidomimetics specifically bind the HER2 protein, and thereby inhibit dimerization. The peptidomimetics disrupt both HER2-HER3 and EGFR-HER2 heterodimer formation. The peptidomimetics can be used in the treatment of various types of HER2-overexpressed cancers, including lung, breast, and ovarian cancers.</p>
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Humanized anti-DKK2 antibody and uses thereof (Fri, 17 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to the discovery that inhibition of Dickkopf2 (DKK2) increases CD8<sup>+</sup> cytotoxic T lymphocyte (CTL) activity, attenuates tumor, and hence suppresses tumor formation. Thus, in various embodiments described herein, the methods of the invention relate to methods of treating cancer by administering to a patient an effective amount of a humanized anti-DKK2 antibody, methods for providing anti-tumor immunity in a subject, methods of stimulating a T cell mediated immune response to a cell population or a tissue and suppressing tumor in a subject. Additionally, the current invention includes methods of diagnosing a cancer or a predisposition of developing a cancer or a metastasis and methods for determining the use of immunotherapy treatment or cancer vaccine for treating cancer. Furthermore, the invention encompasses a pharmaceutical composition for treating cancer as well as a kit for carrying out the aforementioned methods.</p>
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CD70 BINDING MOLECULES AND METHODS OF USE THEREOF (Fri, 17 Aug 2018)
<p id="p-0001" num="0000">The disclosure provides anti-CD70 antibodies, antigen binding fragments thereof, chimeric antigen receptors (CARs) and engineered T cell receptors (TCRs) comprising an antigen binding molecule that specifically binds to CD70, 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 TCR and/or 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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CHIMERIC ANTIGEN RECEPTORS BASED ON SINGLE-DOMAIN ANTIBODIES AND METHODS OF USE THEREOF (Fri, 17 Aug 2018)
<p id="p-0001" num="0000">The present application provides single-domain antibodies, and chimeric antigen receptors comprising one or more antigen binding domains each comprising a single-domain antibody. Further provided are engineered immune effector cells (such as T cells) comprising the chimeric antigen receptors. Pharmaceutical compositions, kits and methods of treating cancer are also provided.</p>
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2-HETEROARYL-3-OXO-2,3-DIHYDROPYRIDAZINE-4-CARBOXAMIDES FOR THE TREATMENT OF CANCER (Fri, 17 Aug 2018)
The present invention covers 2-heteroaryl-3-oxo-2,3-dihydropyridazine-4-carboxamide compounds of general formula (I), in which X, R1, R2, R3, R4 and R5 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 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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IN VIVO STABLE HG-197(M) COMPOUNDS, METHOD FOR THE PRODUCTION THEREOF AND USE THEREOF IN NUCLEAR MEDICAL DIAGNOSTICS AND ENDORADIONUCLIDE THERAPY (THERANOSTICS) (Fri, 17 Aug 2018)
The present invention relates to in vivo stable 197(m)Hg compounds according to formula (I) for use in nuclear medical diagnostics and endoradionuclide therapy (theranostics), particularly the treatment of cancer, a method for the production of the 197(m)Hg compounds comprising the step of radiolabeling of organic precursor compounds with NCA 197(m)Hg by electrophilic substitution; and the use of the 197(m)Hg compounds for nuclear medical diagnostics and endoradionuclide therapy (theranostics), particularly the treatment of cancer.
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NOVEL INHIBITORS OF CELLULAR SIGNALLING (Fri, 17 Aug 2018)
The present disclosure relates generally to Cellular Signalling inhibitors of compound of Formula I, compositions and formulations comprising the same, methods, processes, and uses thereof. In particular, the present disclosure provides CSF-1R inhibitors of BLZ-945-lipids conjugates, GW2580-lipid conjugates and PLX-3397-lipid conjugates demonstrating sustained inhibition of CSF/CSF1R signalling pathway with decreased toxicity. The present disclosure also provides supramolecular combinatorial therapeutics, wherein a CSF-1R inhibitor is combined with one or more of a chemotherapeutic agent, a kinase inhibitor, and an immunoregulator, each of which is optionally conjugated with a lipid. The present disclosure also provides a method for treating cancer, allergy, Systemic lupus erythematosus, nephritis, Chronic Obstructive Pulmonary Disease, and abnormal macrophage functions or any combinations thereof.
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COMPOSITIONS, KITS, AND METHODS TO INDUCE ACQUIRED CYTORESISTANCE USING STRESS PROTEIN INDUCERS (Fri, 17 Aug 2018)
The present disclosure provides compositions, kits, and methods to protect organs by inducing acquired cytoresistance without causing injury to the organ. The compositions, kits, and methods utilize Me-porphryin complexs, heme proteins, iron containing molecules, and/or vitamin B12 and, optionally, agents that impact heme protein metabolism.
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METHODS FOR DETERMINING BREAST CANCER RISK (Fri, 17 Aug 2018)
The present disclosure relates generally to determining the risk of developing breast cancer. In particular, the present disclosure provides materials and methods for determining whether a subject diagnosed with a non-cancerous breast tumor will develop cancer based on expression of multiple oncogenic biomarkers in the non-cancerous breast tumor. The present disclosure also provides a cancer risk score to determine whether a subject has low risk, intermediate risk, or high risk of developing cancer, thereby permitting selection of appropriate therapies to treat the subject. The present disclosure addresses the need for improved diagnostic assessment of early hyperplastic lesions, the presence of which in a subject is a significant indicator that a subject will eventually develop invasive breast cancer.
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AZIDE SCAVENGING RESIN (Fri, 17 Aug 2018)
A TentaGelc™-based azide resin can rapidly remove unreacted alkyne precursor from [18F]fluoroethylazide radiolabeling reactions leading to dramatically increased specific activities.
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MODULATING BIOMARKERS TO INCREASE TUMOR IMMUNITY AND IMPROVE THE EFFICIACY OF CANCER IMMUNOTHERAPY (Fri, 17 Aug 2018)
The present invention relates, in part, to methods of treating a cancer in a subject comprising administering to the subject a therapeutically effective amount of an agent that inhibits one or more biomarkers in Table 1 in combination with an immunotherapy.
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REGULATING CHIMERIC ANTIGEN RECEPTORS (Fri, 17 Aug 2018)
This invention is in the area of compositions and methods for regulating chimeric antigen receptor immune effector cell, for example T-cell (CAR-T), therapy to modulate associated adverse inflammatory responses, for example, cytokine release syndrome and tumor lysis syndrome, using targeted protein degradation.
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TUNABLE ENDOGENOUS PROTEIN DEGRADATION WITH HETEROBIFUNCTIONAL COMPOUNDS (Fri, 17 Aug 2018)
The present invention provides a means to modulate gene expression in vivo in a manner that avoids problems associated with CRISPR endogenous protein knock-out or knock-in strategies and strategies that provide for correction, or alteration, of single nucleotides. The invention includes inserting into the genome a nucleotide encoding a heterobifunctional compound targeting protein (dTAG) in-frame with the nucleotide sequence of a gene encoding an endogenously expressed protein of interest which, upon expression, produces an endogenous protein-dTAG hybrid protein. This allows for targeted protein degradation of the dTAG and the fused endogenous protein using a heterobifunctional compound.
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METHODS FOR THE DETECTION AND TREATMENT OF LUNG CANCER (Fri, 17 Aug 2018)
Provided are methods and related kits for detection of early stage lung cancer, and determination of risk of harboring lung cancer.
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TRIGGER-ACTIVATABLE SUGAR CONJUGATES FOR CANCER-SELECTIVE LABELING AND TARGETING (Fri, 17 Aug 2018)
Disclosed are compounds for the selective labeling of cell-surface sugars in cancer cells. The compounds are activatable by triggers specific to cancer cells, and, when metabolized, label a cancer cell surface sugar with an azide chemical group. Facilitated by a click chemistry reaction, combination of the cell surface-expressed azide with a alkynyl-drug conjugate enables efficient targeted drug delivery to cancer cells with reduced toxicity. Also disclosed are compounds for delivering a drug to an azide-bearing cancer cell, and methods of treating cancer using the compounds.
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HIGHLY SELECTIVE AKR1C3 INHIBITORS AND METHODS OF USE THEREOF (Fri, 17 Aug 2018)
The present invention includes methods and compositions that inhibit AKR1C3 enzymatic activity and consequently reduces androgen receptor (AR) transactivation, AR and prostate specific antigen (PSA) expression levels in, for example, prostate cancer, castration-resistant prostate cancer, breast cancer, acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia (T-ALL), or a leukemia.
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STEROID SAPONINS WITH ANTI-CANCER ACTIVITY (Fri, 17 Aug 2018)
The present invention relates to a new class of steroid saponins that have interesting biological activity. In particular the present invention relates to a class of steroid saponins in which the sugar moiety has been selectively functionalised to introduce a moiety that contains either, (i) a hydrogen ion donor, (ii) a hydrogen ion acceptor or (iii) a combination thereof. These new, water-soluble compounds are found to not only have potent anti-cancer properties per se but also have the ability to promote the immune response in a subject and can thus act as adjuvants for T-cell activation in cancer therapy.
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HUMAN ETS-RELATED GENE (ERG) COMPOUNDS AS THERAPEUTICS AND METHODS FOR THEIR USE (Fri, 17 Aug 2018)
This invention provides compound having a structure of Formula (I): (I) Uses of such compounds for treatment of ERG, FLI1, ETV4, or ETV1 -mediated indications, including cancer. Also provided are pharmaceutical composition and methods of treating ERG, FLI1, ETV4, or ETV1-mediated indications, including cancer. The cancer may be selected from the group consisting of: prostate cancer, Ewing's sarcoma, breast cancer or pancreatic cancer.
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POLYMERIC NANOPARTICLES ENCAPSULATING A COMBINATION OF NATURAL BIO-ACTIVES TRANS-RESVERATROL(RSV) AND CELASTROL(CL), A PROCESS FOR THE PREPARATION AND USE THEREOF IN THE TREATMENT OF PROSTATE CANCER (Fri, 17 Aug 2018)
The present invention relates to polymeric nanoparticles for the combined administration a number of substances of natural origin for the treatment of prostate cancer. Specifically, the present invention relates to nanoparticles based on a blend of poly(ε-caprolactone) and poly(D,L-lactic-co-glycolic acid)-poly(ethylene glycol) loaded with suitable amounts of resveratrol and celastrol. The invention also relates to the preparation of said polymeric nanoparticles loaded with resveratrol and celastrol and to their use for conveying said active substances in the treatment of prostate cancer.
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1-(4-AMINO-5-BROMO-6-(1 H-PYRAZOL-1-YL)PYRIMIDIN-2-YL)-1 H-PYRAZOL-4-OL AND USE THEREOF IN THE TREATMENT OF CANCER (Fri, 17 Aug 2018)
This invention relates to an active metabolite of 5-bromo-2,6-di(1H-pyrazol-1-yl)pyrimindin-4-amine that modulates the activity of adenosine A2a receptor. In particular, the present invention relates to pharmaceutical compositions comprising 1-(4-amino-5-bromo-6-(1H-pyrazol-1-yl)-pyrimidin-2-yl)-1H-pyrazol-4-ol, as well as processes for its preparation and its use in the treatment of cancer alone of in combination with one or more immunotherapeutic agents.
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HETEROBIFUNCTIONAL LINKERS FOR MODIFYING THIOLS (Fri, 17 Aug 2018)
The invention relates to certain compounds of formula (I) (I) wherein Y is an electron-withdrawing group; Q is (formula) Z is a leaving group; J is NR5, with R5 being hydrogen or a substituted or unsubstituted alkyl, alkenyl, alkynyl or aryl group. R1 to R4 optional substituents and m is an integer between 1 and 12; n is an integer between 0 and 4; o is between 0 and 4. These compounds are useful as linkers for realisably joining a targeting moiety such as an antibody to a "cargo" compound such as a drug, particularly an anti-cancer drug. The invention also relates to conjugates of a targeting moiety and a drug utilising the linker, to methods of synthesis of the linker and to processes for the production of the conjugate. The use of the conjugate in the treatment of disease such as cancer is also disclosed.
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SULFINYLPYRIDINES AND THEIR USE IN THE TREATMENT OF CANCER (Fri, 17 Aug 2018)
There is provided compounds of formula I (I) or pharmaceutically-acceptable salts thereof, wherein L, R1, R2, R3, R4 and n have meanings provided in the description, which compounds are useful in the treatment of cancers.
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HETEROARYLSULFONYL-SUBSTITUTED PYRIDINES AND THEIR USE IN THE TREATMENT OF CANCER (Fri, 17 Aug 2018)
There is provided compounds of formula I (I) or pharmaceutically-acceptable salts thereof, wherein L, R1, R2, R3 and X have meanings provided in the description, which compounds are useful in the treatment of cancers.
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HETEROCYCLYLSULFONYL-SUBSTITUTED PYRIDINES AND THEIR USE IN THE TREATMENT OF CANCER (Fri, 17 Aug 2018)
There is provided compounds of formula I (I) or pharmaceutically-acceptable salts thereof, wherein L, R1, R2, R3 and X have meanings5 provided in the description, which compounds are useful in the treatment of cancers.
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HYDROCARBYLSULFONYL-SUBSTITUTED PYRIDINES AND THEIR USE IN THE TREATMENT OF CANCER (Fri, 17 Aug 2018)
There is provided compounds of formula I (I) or pharmaceutically-acceptable salts thereof, wherein L, R1, R2, R3 and X have meanings provided in the description, which compounds are useful in the treatment of cancers.
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HALOGEN-SUBSTITUTED HETEROCYCLIC COMPOUND USEFUL FOR THE TREATMENT OF DISEASES CAUSED BY LPA (Thu, 16 Aug 2018)
A compound represented by the general formula (I) for use in the treatment and/or prevention of a disease accompanying fibrosis, an immunological or inflammatory disease, a central or peripheral nervous system disease, an urologic disease, or a cancer-related disease, more specifically for use in the treatment and/or prevention of non-alcoholic steatohepatitis.
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TARGETING DEREGULATED WNT SIGNALING IN CANCER USING STABILIZED ALPHA-HELICES OF BCL-9 (Thu, 16 Aug 2018)
The invention provides structurally-constrained peptides by hydrocarbon stapling of a BCL9 HD2 helix for use as a therapeutic agent. The invention further provides methods and kits for use of the structurally-constrained peptide of the instant invention. The invention is based, at least in part, on the results provided herein demonstrating that hydrocarbon stapled helical peptides display excellent proteolytic, acid, and thermal stability, restore the native helical structure of the peptide, possess superior pharmacokinetic properties compared to the corresponding unmodified peptides, and are highly effective in binding to ²-catenin in vitro, in cellulo, and in vivo, disrupting the BCL-9/²-catenin interaction, and thereby interfering with deregulated Wnt/²-catenin signaling for therapeutic benefit in a variety of human diseases including human cancer.
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ANTIBODIES BINDING TO AN INTRACELLULAR PRL-1 OR PRL-3 POLYPEPTIDE (Thu, 16 Aug 2018)
We provide an antibody capable of binding to an intracellular PRL-1 or PRL-3 polypeptide, in which the antibody is capable of binding to an epitope bound by an antibody 269, antibody 223 or antibody 318. Such anti-PRL antibodies may be capable of binding to intracellular PRL-1 or PRL-3. They may be suitable for use as therapies against cancer or metastasis thereof, or in clinical diagnosis to identify PRL-3 or PRL-1 positive patients.
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1,2,5-OXADIAZOLES AS INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE (Thu, 16 Aug 2018)
The present invention is directed to 1,2,5-oxadiazole derivatives, and compositions of the same, which are inhibitors of indoleamine 2,3-dioxygenase and are useful in the treatment of cancer and other disorders, and to the processes and intermediates for making such 1,2,5-oxadiazole derivatives.
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BROMODOMAIN INHIBITORS (Thu, 16 Aug 2018)
The present invention provides for compounds of formula (I) wherein A 1 , A 2 , A 3 , A 4 , X 1 , X 2 , Y 1 , L 1 , G 1 , R x , and R y 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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METHODS FOR DIAGNOSIS OF THYROID CONDITIONS (Thu, 16 Aug 2018)
Methods for molecular profiling and cancer diagnosis
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METHOD OF TREATING CANCER WITH A COMBINATION OF BENZYLIDENEGUANIDINE DERIVATIVES AND CHEMOTHERAPEUTIC AGENT (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to a composition for use in treating a glioma or ameliorating the effects of a glioma, particularly glioblastoma, wherein said composition comprises a first active agent selected from the group consisting of a compound of formula (I), or a pharmaceutically acceptable salt thereof, (I) and a second active agent, which is temozolomide, or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="21.59mm" wi="60.37mm" file="US20180221310A1-20180809-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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3-(1H-PYRROLO[3,2-C]PYRIDIN-2-YL)-1H-PYRAZOLO[3,4-B]PYRIDINES AND THERAPEUTIC USES THEREOF (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">7-Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of a 7-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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3-(1H-PYRROLO[3,2-C]PYRIDIN-2-YL)-1H-INDAZOLES AND THERAPEUTIC USES THEREOF (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, 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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3-(1H-PYRROLO[2,3-C]PYRIDIN-2-YL)-1H-PYRAZOLO[3,4-C]PYRIDINES AND THERAPEUTIC USES THEREOF (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">6-Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of a 6-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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3-(3H-IMIDAZO[4,5-C]PYRIDIN-2-YL)-1H-PYRAZOLO[4,3-B]PYRIDINES AND THERAPEUTIC USES THEREOF (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">4-Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of a 4-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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METHODS AND COMPOSITIONS USEFUL FOR TREATING DISEASES INVOLVING BCL-2 FAMILY PROTEINS WITH QUINOLINE DERIVATIVES (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to compositions and methods for cancer treatment comprising compounds of Formulae I, II, and III. In some aspects, the invention relates to the treatment of B-cell Lymphoma or other hematopoietic cancers. In other aspects, the invention provides methods for treating particular types of hematopoietic cancers, such as, for example, B-cell lymphoma, using a combination of one or more compounds of Formulae I, II, and III. Combination therapy with, for example, 26S proteasome inhibitors, such as, for example, Bortezomib, are also included. In another aspect the present invention relates to autoimmune treatment with compounds of Formulae I, II, and III. In another aspect, this invention relates to methods for identifying compounds, for example, compounds of the BH3 mimic class, that have in vitro properties that predict in vivo efficacy against B-cell lymphoma tumors and other cancers as well as autoimmune disease.</p>
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APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-xL proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-xL protein.</p>
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ANTIPROLIFERATIVE COMPOUNDS AND METHODS OF USE THEREOF (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">Compounds of formula I for treating, preventing or managing cancer are disclosed. Also disclosed are methods of treating, preventing or managing cancer, such as leukemia, comprising administering the compounds. In certain embodiments, the method of treatment comprise administering a compound provided herein in combination with a second agent. Pharmaceutical compositions and single unit dosage forms comprising the compounds are also disclosed.</p>
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IMIPRIDONES FOR GLIOMAS (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">Imipridones selectively modulate Class A G protein-coupled receptors (GPCRs), such as the D2-like subfamily of dopamine receptors, and are useful for treating conditions and disorders in need of such modulation, such as cancers. Specifically, the cancer is a midline glioma, a cancer having a histone H3 mutation, or both. In addition, methods of identifying whether a subject having these conditions, is likely to be responsive to a treatment regimen, such as imipridone administration, are provided. Furthermore, methods of assessing the effectiveness of a treatment regimen, such as imipridone administration, monitoring, or providing a prognosis for a subject with these condition are also provided.</p>
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NOVEL MODULATORS OF CALCIUM RELEASE-ACTIVATED CALCIUM CHANNEL (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">Disclosed are novel calcium release-activated calcium (CRAC) channel inhibitors, methods for preparing them, pharmaceutical compositions containing them, and methods of treatment using them. The present disclosure also relates to methods for treating non-small cell lung cancer (NSCLC) with CRAC inhibitors, and to methods for identifying therapeutics for treating and of diagnosing cancer.</p>
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BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to certain bis-heteroaryl compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer including melanoma.</p>
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TRICYCLIC HETEROCYCLES AS BET PROTEIN INHIBITORS (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The present disclosure relates to tricyclic heterocycles which are inhibitors of BET proteins such as BRD2, BRD3, BRD4, and BRD-t and are useful in the treatment of diseases such as cancer.</p>
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3-(3H-IMIDAZO[4,5-B]PYRIDIN-2-YL)-1H-PYRAZOLO[4,3-B] PYRIDINES AND THERAPEUTIC USES THEREOF (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">4-Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of a 4-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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PRODRUGS OF GLUTAMINE ANALOGS (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The disclosure provides compounds having formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="19.39mm" wi="61.38mm" file="US20180222930A1-20180809-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and the pharmaceutically acceptable salts thereof, wherein R<sub>1</sub>, R<sub>2</sub>, R<sub>2</sub>′, and X are as defined as set forth in the specification. Compounds having formula (I) are prodrugs that release glutamine analogs, e.g., 6-diazo-5-oxo-L-norleucine (DON). The disclosure also provides compounds having formula (I) for use in treating cancer.</p>
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DIPEPTIDOMIMETICS AS INHIBITORS OF HUMAN IMMUNOPROTEASOMES (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The compounds of the present invention are represented by the following compounds having Formula I, where the substituents R1, R4, L, M, X, Y, and s are as defined herein. The compounds of the present invention are also represented by the following compounds having Formula (Ia), Formula (Ib), or Formula (Ic), where the substituents R1-R4, RX, RY, X, Y, and s are as defined herein. These compounds are used in the treatment of cancer, immunologic disorders, autoimmune disorders, neurodegenerative disorders, or inflammatory disorders or for providing immunosuppression for transplanted organs or tissues.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="113.54mm" wi="69.85mm" file="US20180221431A1-20180809-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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N-SUBSTITUTED PYRAZOLYL GUANIDINE F1F0-ATPASE INHIBITORS AND THERAPEUTIC USES THEREOF (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The invention provides pyrazolyl guanidine compounds that inhibit F<sub>1</sub>F<sub>0</sub>-ATPase, and methods of using pyrazolyl guanidine compounds as therapeutic agents to treat medical disorders, such as an immune disorder, inflammatory condition, or cancer.</p>
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ANTICANCER DRUGS INCLUDING THE CHEMICAL STRUCTURES OF AN ANDROGEN RECEPTOR LIGAND AND A HISTONE DEACETYLASE INHIBITOR (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">A novel class of drugs for treating androgen receptor (AR) positive cancer including prostate cancer and breast cancer are described. The drugs include the chemical scaffolds of a high affinity androgen receptor ligand and a histone deacetylase inhibitor. Also described are compositions including the novel drugs and methods of treating AR positive cancer using the compositions.</p>
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COMPOUNDS USEFUL FOR TREATING CANCER (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to a compound of formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="15.92mm" wi="69.85mm" file="US20180222888A1-20180809-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein A and A′ independently represent a phenylene group or a pyridylene group; R<sub>2 </sub>is a hydrogen atom or a (C<sub>1</sub>-C<sub>4</sub>)alkyl group; R<sub>3 </sub>is a 2-pyridyl group, 3-pyridyl group, a 4-pyridyl group, a 2-pyrimidinyl group, a 4-pyrimidinyl group or a 5-pyrimidinyl group; R<sub>4 </sub>is a carbonyl group or a sulfonyl group; and R<sub>5 </sub>is a —NH—(CH<sub>2</sub>)<sub>a</sub>—NR<sub>6</sub>R<sub>7 </sub>group or a 4-methylpiperazinyl group, with a being an integer from 1 to 4, R<sub>6 </sub>and R<sub>7 </sub>representing independently a (C<sub>1</sub>-C<sub>4</sub>)alkyl group, or R<sub>6 </sub>and R<sub>7 </sub>together with the nitrogen atom to which they are linked forming a heterocycle group which is chosen among a 4-methylpiperazinyl group, a morpholino group, a pyrrolidinyl group and a piperidino group; or any one of its pharmaceutically acceptable salt.</p>
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3-(1H-INDOL-2-YL)-1H-INDAZOLES AND THERAPEUTIC USES THEREOF (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, 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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SUBSTITUTED NICOTINIMIDE INHIBITORS OF BTK AND THEIR PREPARATION AND USE IN THE TREATMENT OF CANCER, INFLAMMATION AND AUTOIMMUNE DISEASE (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">Compounds of Formula I, as shown below and defined herein:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.52mm" wi="69.85mm" file="US20180222897A1-20180809-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">and pharmaceutically acceptable salts, syntheses, intermediates, formulations, and methods of treating diseases including cancer, inflammation, and autoimmune disease mediated at least in part by Bruton's Tyrosine Kinase (BTK).</li> </ul> </li> </ul> </p>
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COMPOSITIONS AND METHODS FOR INHIBITING ARGINASE ACTIVITY (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The disclosure relates to a novel class of compounds that exhibit activity inhibitory activity toward arginase, and pharmaceutical compositions comprising the compounds of the disclosure. Also provided herein are methods of treating cancer with the arginase inhibitors of the disclosure.</p>
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STAT6 INHIBITORS (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The present disclosure provides compounds that are useful for inhibiting the STAT6 pathway. Also provided are related pharmaceutical compositions and methods of using the compounds. In some embodiments, the compounds may be used to treat a disease such as, e.g., an allergic lung disease, allergic rhinitis, chronic pulmonary obstructive disease, or a cancer.</p>
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LYMPHOTOXIN-BETA RECEPTOR-BINDING AGENTS, TARGETING ANTIBODIES, AND USES THEREOF (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">Polypeptides, agents, and molecules that bind lymphotoxin-beta receptor (LTβR) and/or tumor-associated antigens are disclosed. The polypeptides, agents, or molecules may include, without limitation, fusion or single-chain lymphotoxin-αββ polypeptides and homodimer and heterodimer molecules comprising the lymphotoxin-αββ polypeptides. Antibodies that specifically bind B7-H4 and P-CADHERIN are also disclosed. Also disclosed are methods of using the polypeptides, agents, molecules, or antibodies for inducing and/or enhancing the immune response, as well as methods for the treatment of diseases such as cancer.</p>
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ANTI-CD3 ANTIBODIES, ANTI-CD123 ANTIBODIES AND BISPECIFIC ANTIBODIES SPECIFICALLY BINDING TO CD3 AND/OR CD123 (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The present invention concerns antibody-like binding protein specifically binding to CD3 and binding specifically to at least one further antigen, for example CD123. The present invention also concerns antibody-like binding protein specifically binding to CD123 and binding specifically to at least one further antigen. The invention further concerns anti-CD3 antibodies and anti-CD123 antibodies. The invention also relates to pharmaceutical compositions comprising the antibody-like binding protein, anti-CD3 antibodies or anti-CD123 antibodies of the invention, and their use to treat cancer. The invention further relates to isolated nucleic acids, vectors and host cells comprising a sequence encoding said antibody-like binding protein, anti-CD3 or anti-CD123 antibody and the use of said anti-CD123 antibody as a diagnostic tool.</p>
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IDENTIFICATION OF PREDICTIVE BIOMARKERS ASSOCIATED WITH WNT PATHWAY INHIBITORS (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The present invention provides biomarkers for identifying tumors likely to respond to treatment with Wnt pathway inhibitors. Also provided are methods for identifying tumors and/or patients that are likely to be responsive or non-responsive to treatment with a Wnt pathway inhibitor. Methods for treating a patient with cancer are provided, wherein the cancer is predicted to respond to a Wnt pathway inhibitor.</p>
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3-(1H-PYRROLO[2,3-C]PYRIDIN-2-YL)-1H-PYRAZOLO[3,4-B]PYRIDINES AND THERAPEUTIC USES THEREOF (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">7-Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of a 7-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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3-(1H-IMIDAZO[4,5-C]PYRIDIN-2-YL)-1H-PYRAZOLO[4,3-B]PYRIDINES AND THERAPEUTIC USES THEREOF (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">4-Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of a 4-azaindazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.</p>
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USES OF SALT-INDUCIBLE KINASE (SIK) INHIBITORS (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The present disclosure provides methods of treating and/or preventing inflammatory bowel disease (IBD) and graft-versus-host disease (GVHD) using salt-inducible kinase (SIK) inhibitors, such as macrocyclic SIK inhibitors of Formula (I), imidazolyl SIK inhibitors of Formula (II), and urea and carbamate SIK inhibitors of Formula (III-A) (e.g., urea and carbamate SIK inhibitors of Formula (III)).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="162.81mm" wi="72.81mm" file="US20180221379A1-20180809-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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SSTR-TARGETED CONJUGATES AND PARTICLES AND FORMULATIONS THEREOF (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">Conjugates of an active agent such as DM1 attached to a targeting moiety, such as a somatostatin receptor binding moiety, via a linker, and particles comprising such conjugates have been designed. Such conjugates and particles can provide improved temporospatial delivery of the active agent, improved biodistribution and penetration in tumor, and/or decreased toxicity. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer.</p>
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DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The present invention concerns a compound of following formula (I): where: —R<sub>1 </sub>is H or OH, —R<sub>2 </sub>is a (C<sub>1</sub>-C<sub>6</sub>)alkyl, COOH, COO—((C<sub>1</sub>-C<sub>6</sub>)alkyl) or thiazolyl group, —R<sub>3 </sub>is H or a (C<sub>1</sub>-C<sub>6</sub>)alkyl group, and —R<sub>4 </sub>is: ▪a straight-chain or branched, saturated or unsaturated hydrocarbon group having 1 to 8 carbon atoms substituted by one or more groups chosen from among OH and NR<sub>5</sub>R<sub>6</sub>, ▪—(CH<sub>2</sub>CH<sub>2</sub>X<sub>1</sub>)(CH<sub>2</sub>CH<sub>2</sub>X<sub>2</sub>)<sub>a2</sub>(CH<sub>2</sub>CH<sub>2</sub>X<sub>3</sub>)<sub>a3</sub>(CH<sub>2</sub>CH<sub>2</sub>X<sub>4</sub>)<sub>a4</sub>(CH<sub>2</sub>CH<sub>2</sub>X<sub>5</sub>)<sub>a5</sub>R<sub>7</sub>, ▪an aryl-(C<sub>1</sub>-C<sub>8</sub>)alkyl group substituted by one or more groups chosen from among OH and NR<sub>9</sub>R<sub>10 </sub>groups, or ▪a heterocycle-(C<sub>1</sub>-C<sub>8</sub>)alkyl group optionally substituted by one or more groups chosen from among (C<sub>1</sub>-C<sub>6</sub>)alkyl, OH and NR<sub>12</sub>R<sub>13 </sub>groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="43.60mm" wi="75.61mm" file="US20180222858A1-20180809-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NOVEL 3-INDOL SUBSTITUTED DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">A compound of Formula I is provided:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="43.01mm" wi="57.07mm" file="US20180222862A1-20180809-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">or pharmaceutically acceptable enantiomers, salts or solvates thereof. The invention further relates to the use of the compounds of Formula I as TDO2 inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity. The invention also relates to a process for manufacturing compounds of Formula I.</li> </ul> </li> </ul> </p>
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ISOQUINOLIN-3-YL CARBOXAMIDES AND PREPARATION AND USE THEREOF (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">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.</p>
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N-(PYRIDIN-2-YL)-4-(THIAZOL-5-YL)PYRIMIDIN-2-AMINE DERIVATIVES AS THERAPEUTIC COMPOUNDS (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">A novel class of inhibitors of protein kinases that are useful in the treatment of cell proliferative diseases and conditions, and especially those characterised by over-expression of CDK4, CDK6 and/or cyclin D, including certain cancers of lung, breast, brain, central nervous system, colorectal cancer and leukaemias. The inhibitors have the general structure I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.18mm" wi="59.69mm" file="US20180222900A1-20180809-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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MODIFIED CYTOTOXINS AND THEIR THERAPEUTIC USE (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The present disclosure generally provides compounds useful for treating cancer. In some aspects, the disclosure provides small-molecule cytotoxins that are chemically modified to include one or more moieties that include hydrophobic portions. In some embodiments, the disclosure provides small-molecule cytotoxins that are chemically modified with fatty acid-containing moieties. In some aspects, the disclosure provides compositions, such as pharmaceutical compositions, that include such modified small-molecule cytotoxins and a protein. In some embodiments, the protein is albumin or an albumin mimetic. Further, the disclosure provides various uses of these compounds and compositions.</p>
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COMPOSITIONS AND METHODS FOR TREATING LEUKEMIA (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The invention provides compositions, methods, and kits for the treatment of acute myeloid leukemia in a subject.</p>
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USING PHAGE EPITOPES TO PROFILE THE IMMUNE RESPONSE (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The present disclosure provides compositions and methods for using one or more polypeptide probes to profile an immune response. The polypeptide probe can be used to detect one or more antibodies from a sample. Furthermore, the present disclosure provides methods and compositions for characterizing a cancer based on the detection of one or more antibodies, such as autoantibodies.</p>
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METHODS FOR DETERMINING BREAST CANCER RISK (Fri, 10 Aug 2018)
<p id="p-0001" num="0000">The present disclosure relates generally to determining the risk of developing breast cancer. In particular, the present disclosure provides materials and methods for determining whether a subject diagnosed with a non-cancerous breast tumor will develop cancer based on expression of multiple oncogenic biomarkers in the non-cancerous breast tumor. The present disclosure also provides a cancer risk score to determine whether a subject has low risk, intermediate risk, or high risk of developing cancer, thereby permitting selection of appropriate therapies to treat the subject. The present disclosure addresses the need for improved diagnostic assessment of early hyperplastic lesions, the presence of which in a subject is a significant indicator that a subject will eventually develop invasive breast cancer.</p>
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DERIVATIVES OF N-CYCLOALKYL/HETEROCYCLOALKYL-4-(IMIDAZO [1,2-a]PYRIDINE)PYRIMIDIN-2-AMINE AS THERAPEUTIC AGENTS (Fri, 10 Aug 2018)
A novel class of inhibitors of protein kinases that are useful in the treatment of cell proliferative diseases and conditions, and especially those characterised by over-expression of one or more CDK enzyme and/or by one or more aberrant CDK activity, including certain cancers of lung, breast, brain, ovary, prostate, colorectal cancer and leukaemias. The inhibitors have the general structure (I).
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METHODS AND COMPOUNDS FOR DETECTION AND BINDING OF ALEDHYDES (Fri, 10 Aug 2018)
Methods of detecting an aldehyde-containing compound in a subject or in a sample from a subject are described herein, comprising administering an aldehyde-binding compound of Formula I to the subject, or combining such a compound with the sample; and detecting the product of the compound of Formula I and the aldehyde-containing compound. Detection of the product may involve imaging, such as MRI, CEST-MRI or positron emission tomography (PET) imaging; or may involve fluorescence or an electrochemical detection method. Biologically relevant aldehydes detected according to the described method can be used to monitor conditions such as brain injury, neurodegenerative disorders such as Alzheimer's disease, diabetes, heart disease, and cancer. Formula (I)
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COMPOUNDS, COMPOSITIONS AND METHODS FOR CANCER TREATMENT (Fri, 10 Aug 2018)
The present invention features improved compounds, especially the compound having the structure (1). Compositions and methods of identifying patients having cancer using biomarkers (e.g., PDE3A, PDE3B, SLFN12 and/or CREB3L1) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention.
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CANCER TREATMENT (Fri, 10 Aug 2018)
The present invention provides a method for the treatment of cancer with erdafitinib.
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ANTI-CCR7 ANTIBODY DRUG CONJUGATES (Fri, 10 Aug 2018)
This application discloses anti-CCR7 antibodies, antigen binding fragments thereof, and antibody drug conjugates of said antibodies or antigen binding fragments. The invention also relates to methods of treating or preventing cancer using the antibodies, antigen binding fragments, and antibody drug conjugates. Also disclosed herein are methods of making the antibodies, antigen binding fragments, and antibody drug conjugates, and methods of using the antibodies and antigen binding fragments as diagnostic reagents.
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INHIBITORS OF MICROBIAL BETA-GLUCURONIDASE ENZYMES AND USES THEREOF (Fri, 10 Aug 2018)
Methods utilizing compounds and compositions are provided that comprise selective β-glucuronidase inhibitors. The methods can ameliorate the side effects of chemotherapeutic agents and can improve the efficacy of such agents, including irinotecan and non-steroidal anti-inflammatory drugs. The methods comprise administering the compounds in combination with agents or administering the compounds in a monotherapy for the treatment of cancer and gastrointestinal conditions.
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N1 -(4-(5-(CYCLOPROPYLMETHYL)-1 -METHYL-1 H-PYRAZOL-4-YL)PYRIDIN-2-YL)CYCLOHEXANE-1,4-DIAMINE DERIVATIVES AND RELATED COMPOUNDS AS CK1 AND/OR IRAKI INHIBITORS FOR TREATING CANCER (Fri, 10 Aug 2018)
The present invention provides pyrazole derivatives of Formula (I), and in particular N1-(4-(5-(cyclopropylmethyl)-1-methyl-lH-pyrazol-4-yl)pyridin-2-yl)cyclohexane-1,4-diamine derivatives and related compounds as casein kinase 1 (CK1) and/or interleukin 1 receptor associated kinase 1 (IRAKI) inhibitors for treating cancer, inflammatory and immune related disorders.
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AGENTS THAT INHIBIT NGLY1 AND METHODS OF USE THEREOF (Fri, 10 Aug 2018)
Methods are provided for treatment of cancer cells, in a regimen comprising contacting the cancer cells with an inhibitor on NGly1, optionally in combination with a direct proteasome inhibitor.
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METHODS FOR TREATING HEMATOLOGICAL CANCER AND THE USE OF BIOMARKERS AS A PREDICTOR FOR RESPONSIVENESS TO TREATMENT COMPOUNDS (Fri, 10 Aug 2018)
A method for predicting the responsiveness of a patient having a hematological cancer to a treatment compound, comprising obtaining a biological sample from the patient having the hematological cancer; determining the expression level of one, two, three, four, five, or more genes; and comparing the expression level of the one, two, three, four, five, or more genes in the biological sample with a reference expression level of the same genes, wherein the treatment compound is 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)- piperidine-2,6-dione (lenalidomide), 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)- piperidine-2,6-dione (Compound A), or a stereoisomer, pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or a polymorph thereof.
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FUSED 1,4-DIAZEPINES AS BET BROMODOMAIN INHIBITORS (Fri, 10 Aug 2018)
The present disclosure provides fused 1,4-diazepines represented by Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein A, E, R1, R2, R3, R4, R5, and Ar are as defined as set forth in the specification. The present disclosure is also directed to the use of compounds having Formula (I) to treat diseases, conditions, or disorders responsive to inhibition of BET bromodomain proteins such as cancer.
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COMBINATION OF VPS34 INHIBITORS AND MTOR INHIBITORS (Fri, 10 Aug 2018)
Disclosed are methods for the treatment of cancer in patients in need of such treatment. The methods comprise administering to such a patient a VPS34 inhibitor such as is N-{6-chloro-4-methyl-2'- [(2-methylpyrimidin-4-yl)amino]-3,4'-bipyridin-5-yl} -2,4-difluorobenzenesulfonamide or a pharmaceutically acceptable salt in combination with an mTOR inhibitor. Also disclosed are medicaments for use in the treatment of cancer.
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COMPOSITIONS AND METHODS FOR MODULATING PPP2R1A (Fri, 10 Aug 2018)
Disclosed herein, inter alia, are compositions and methods useful for modulating PPP2R1 A and for the treatment of cancer.
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TARGETED ENGINEERED INTERFERON AND USES THEREOF (Fri, 10 Aug 2018)
The present invention relates to chimeric proteins comprising a consensus interferon as a signaling agent. In some embodiments, the consensus interferon is modified and comprises one or more mutations. In an embodiment, the modified consensus interferon comprise one or more mutations that reduce its affinity for IFNAR1 and comprises one or more mutations that reduce its affinity for IFNAR2. The present invention provides pharmaceutical compositions comprising the chimeric proteins and their use in the treatment of various diseases. The present invention relates to a method for treating cancer, comprising administering an effective amount of the chimeric protein.
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1,3,4-thiadiazole compounds and their use in treating cancer (Wed, 08 Aug 2018)
<p id="p-0001" num="0000">A compound of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.21mm" wi="72.14mm" file="US10040789-20180807-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">or a pharmaceutically acceptable salt thereof, is described. Q can be pyridazin-3-yl, 6-fluoropyridazin-3-yl; R<sup>1 </sup>can be H; R<sup>2 </sup>and R<sup>3 </sup>can each independently be C1-C6 alkyl, or R<sup>2 </sup>and R<sup>3 </sup>taken together are —(CH<sub>2</sub>)<sub>3</sub>—; or R<sup>1 </sup>and R<sup>2 </sup>taken together can be —(CH<sub>2</sub>)<sub>2</sub>— and R<sup>3 </sup>can be —CH<sub>3</sub>; R<sup>4 </sup>halo, —CH<sub>3</sub>, —OCH<sub>3</sub>, —OCHF<sub>2</sub>, —OCF<sub>3</sub>, or —CN; and n can be 0, 1, or 2. The compound of formula (I) can inhibit glutaminase, e.g., GLS1.</li> </ul> </li> </ul> </p>
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3-(1H-PYRROLO[3,2-C]PYRIDIN-2-YL)-1H-PYRAZOLO[3,4-C]PYRIDINES AND THERAPEUTIC USES THEREOF (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">6-Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of a 6-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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3-(1H-INDOL-2-YL)-1H-PYRAZOLO[3,4-B]PYRIDINES AND THERAPEUTIC USES THEREOF (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">7-Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of a 7-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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AZOLOPYRIMIDINE FOR THE TREATMENT OF CANCER-RELATED DISORDERS (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">Compound that is an inhibitor of at least one of the A<sub>2A </sub>and A<sub>2B </sub>adenosine receptors, and compositions containing the compound and methods for synthesizing the compound, are described herein. The use of such compound and compositions for the treatment of a diverse array of diseases, disorders, and conditions, including cancer- and immune-related disorders that are mediated, at least in part, by the adenosine A<sub>2A </sub>receptor and/or the adenosine A<sub>2B </sub>receptor.</p>
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INHIBITORS OF ACK1/TNK2 TYROSINE KINASE (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">Described are cancer therapies and anti-cancer compounds. In particular, disclosed are inhibitors of ACK1 tyrosine kinase and their use in the treatment of cancer. Methods of screening for new ACK1 tyrosine kinase inhibitors are also disclosed. In specific example, compound having Formula I are disclosed.</p>
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PROTEASOME CHYMOTRYPSIN-LIKE INHIBITION USING PI-1833 ANALOGS (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">Focused library synthesis and medicinal chemistry on an oxadiazole-isopropylamide core proteasome inhibitor provided the lead compound that strongly inhibits CT-L activity. Structure activity relationship studies indicate the amide moiety and two phenyl rings are sensitive toward synthetic modifications. Only para-substitution in the A-ring was important to maintain potent CT-L inhibitory activity. Hydrophobic residues in the A-ring's para-position and meta-pyridyl group at the B-ring significantly improved inhibition. The meta-pyridyl moiety improved cell permeability. The length of the aliphatic chain at the para position of the A-ring is critical with propyl yielding the most potent inhibitor, whereas shorter (i.e. ethyl, methyl or hydrogen) or longer (i.e. butyl, propyl and hexyl) chains demonstrating progressively less potency. Introduction of a stereogenic center next to the ether moiety (i.e. substitution of one of the hydrogens by methyl) demonstrated chiral discrimination in proteasome CT-L activity inhibition (the S-enantiomer was 35-40 fold more potent than the R-enantiomer).</p>
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TETRAHYDROQUINOLINE COMPOSITIONS AS BET BROMODOMAIN INHIBITORS (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to inhibitors of bromo and extra terminal (BET) bromodomains that are useful for the treatment of cancer, inflammatory diseases, diabetes, and obesity, having Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.01mm" wi="32.51mm" file="US20180215766A1-20180802-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein W, X, Y, Z, R<sup>1</sup>, R<sup>2</sup>, R<sup>5</sup>, and R<sup>8 </sup>are as described herein.</p>
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PD-L1 PROMOTER METHYLATION IN CANCER (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">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.</p>
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A MEK1 Mutation Conferring Resistance to RAF and MEK Inhibitors (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.</p>
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TREATMENT METHOD UTILIZING PYRROLIDINE-2, 5-DIONE DERIVATIVES AS IDO1 INHIBITORS (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">Uses of compound of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.36mm" wi="33.95mm" file="US20180214415A1-20180802-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable enantiomers, salts, solvates or prodrugs thereof are described. The compounds of Formula I are useful as IDO1 inhibitors. These are also useful for the treatment and/or prevention of cancer and endometriosis.</p>
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IMMUNOTHERAPY WITH BINDING AGENTS (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">Binding agents that modulate the immune response are disclosed. The binding agents may include soluble receptors, polypeptides, and/or antibodies. Also disclosed are methods of using the binding agents for the treatment of diseases such as cancer.</p>
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MODULATION OF SRPX2-MEDIATED ANGIOGENESIS (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to nucleic acids and antibodies against SRPX2 and SRPX2 protein function in angiogenesis. Angiogenesis-related conditions, such as cancer or wound healing, can be treated by the composition comprising the SRPX2 antagonists or agonists, respectively.</p>
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Novel Aminothiazole Compounds and Methods Using Same (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">The present invention includes novel aminothiazole compounds useful in preventing or treating cancer in a subject in need thereof. The present invention also includes methods of preventing or treating cancer in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention.</p>
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1-SUBSTITUTED 1,2,3,4-TETRAHYDRO-1,7-NAPHTHYRIDIN-8-AMINE DERIVATIVES AND THEIR USE AS EP4 RECEPTOR ANTAGONISTS (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">The present invention provides a compound represented by the formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.24mm" wi="57.23mm" file="US20180215754A1-20180802-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as defined in the specification, or a salt thereof has an EP4 receptor antagonistic action, and is useful as an agent for the prophylaxis or treatment of EP4 receptor associated diseases (e.g., rheumatoid arthritis, aortic aneurysm (e.g. abdominal aortic aneurysm, thoracic aortic aneurysm, thoracoabdominal aortic aneurysm etc.), endometriosis, ankylosing spondylitis, inflammatory breast cancer etc.) and the like.</p>
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3-(1H-PYRROLO[3,2-C]PYRIDIN-2-YL)-1H-PYRAZOLO[4,3-B]PYRIDINES AND THERAPEUTIC USES THEREOF (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">4-Azaindazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of a 4-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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Method for producing benzazoloquinolium (BQs) salts and using the biological activity of the composition (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">Disclosed is the synthesis procedure for benzazolo[3,2-a]quinolinium chloride salts and the inclusion of chloro-substituent, amino-substituent, and nitro-substituent resulting in several compounds. The compounds are further used as markers due to their fluorescent properties including in hypoxic environments.</p> <p id="p-0002" num="0000">This disclosure further describes anti-cancer screening of two BQS, namely, 7-benzyl-3-aminobenzimidazo[3,2-a]quinolinium chloride (ABQ-48: NSC D-763307) and the corresponding 7-benzyl-3-nitrobenzimidazo[3,2-a]quinolinium chloride (NBQ 48: NSC D-763303).</p>
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NOVEL COMPOUND HAVING BLT INHIBITORY ACTIVITY AND COMPOSITION, FOR PREVENTING OR TREATING INFLAMMATORY DISEASES, COMPRISING SAME AS ACTIVE INGREDIENT (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to a novel compound showing leukotriene B4 receptor 2 (BLT2) inhibitory activity and a pharmaceutical composition, for preventing or treating inflammatory diseases, having same as an active ingredient. The inventors identified a novel compound containing BTL2 inhibitory activity, and experimentally confirmed that the present novel compound had an excellent effect on the enhancement of the cancer cell death, on the inhibition of the metastasis and chemotactic mobility, and on the anti-asthma activity. Therefore, the present novel compound can be used as a very effective pharmaceutical component for treating the inflammatory-related diseases.</p>
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TYPE III DEIODINASE INHIBITORS AND USES THEREOF (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to compounds that inhibit the activity of Type III deiodinase (DIO3). The present invention further relates to methods for treating or preventing depression, depression associated with other psychiatric or general medical diseases or conditions, condition amenable to treatment with known anti-depressants and cancer, particularly by using the compounds of the invention.</p>
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SMALL MOLECULE ANDROGEN RECEPTOR INHIBITORS AND METHODS OF USE THEREOF (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">Small molecule carbazole compounds for use as androgen receptor inhibitors are provided herein. Also provided herein are methods for using the carbazole compounds in treating prostate cancer, including castration-resistant prostate cancer and enzalutamide-resistant prostate cancer. The methods include administering to a subject an effective amount of a compound or composition as described herein.</p>
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TEAD TRANSCRIPTION FACTOR AUTOPALMITOYLATION INHIBITORS (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">The present disclosure compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the TEAD transcription factor, and are useful in the treatment of diseases related to the activity of TEAD transcription factor including, e.g., cancer and other diseases.</p>
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Substituted Hydrophobic Benzene Sulfonamide Thiazole Compounds for Use in Treating Cancer (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to compound of general formula (I) R<sub>1 </sub>is selected from H, aryl and alkyl, R<sub>2 </sub>is selected from H, alkyl, aryl and CO—R<sub>6</sub>; R<sub>3 </sub>is selected from H, halogen, alkyl, alkenyl, alkynyl, aryl, NHR<sub>7</sub>, NR<sub>7</sub>R<sub>8</sub>, OR<sub>7 </sub>and SR<sub>7</sub>; R<sub>4 </sub>is selected from (C<sub>6</sub>-C<sub>12</sub>) alkyl, (C<sub>2</sub>-C<sub>12</sub>) alkenyl, (C<sub>2</sub>-C<sub>12</sub>) alkynyl and (C<sub>6</sub>-C<sub>10</sub>) aryl, R<sub>5 </sub>represents H, R<sub>6</sub>, aryl, OH, OR<sub>6</sub>, O-aryl, SH, SR<sub>6</sub>, S-aryl, CN, NO<sub>2</sub>, CF<sub>3</sub>, COOR<sub>6</sub>, SO<sub>2</sub>NR<sub>6</sub>R<sub>7</sub>, CONR<sub>6</sub>R<sub>7</sub>, NH<sub>2</sub>, NHR<sub>6</sub>, NH-aryl, NR<sub>6</sub>R<sub>7</sub>, NHCOR<sub>6 </sub>or aminoacyl; R<sub>6 </sub>is alkyl optionally substituted with halogen, OH, SH, NH<sub>2</sub>, O-alkyl, S-alkyl, NH-alkyl or NH-di(alkyl); R<sub>7 </sub>and R<sub>8 </sub>identical or different are H or alkyl optionally substituted with halogen, OH, SH, NH<sub>2</sub>, O-alkyl, S-alkyl, NH-alkyl or NH-di (alkyl), their pharmaceutically acceptable salts and/or isomers, tautomers, solvates or isotopic variations thereof. The compounds are useful for the treatment of cancers.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.94mm" wi="71.37mm" file="US20180215723A1-20180802-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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POLYMORPHS OF SELINEXOR (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">The present invention relates to crystalline forms of the compound represented by Structural Formula I, and compositions comprising crystalline forms of the compound represented by Structural Formula I described herein. The crystalline forms of the compound of Structural Formula I and compositions comprising the crystalline forms of the compound of Structural Formula I provided herein, in particular, single crystalline Form A, can be incorporated into pharmaceutical compositions, which can be used to treat various disorders associated with CRM1 activity, including cancer. Also described herein are methods for preparing the compound of Structural Formula I and its single crystalline forms.</p>
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2-(1H-INDAZOL-3-YL)-1H-IMIDAZO[4,5-C]PYRIDINE AND THERAPEUTIC USES THEREOF (Fri, 03 Aug 2018)
<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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TGF BETA RECEPTOR ANTAGONISTS (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">The invention relates generally to compounds that modulate the activity of TGFβR-1 and TGFβR-2, pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="40.64mm" wi="61.04mm" file="US20180215762A1-20180802-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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TGF BETA RECEPTOR ANTAGONISTS (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">The invention relates generally to compounds that modulate the activity of TGFβR-1 and TGFβ R-2, pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.</p>
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CONJUGATES THAT ARE CONFIGURED FOR TARGETED DELIVERY OF THERAPEUTIC COMPOUNDS TO SENESCENT CELLS (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">Disclosed are agents (e.g., peptides, polypeptides, proteins, small molecules, antibodies, and antibody fragments that target senescent cells) and methods of their use for imaging senescent cells in vivo and for treating or preventing cancer, age-related disease, tobacco-related disease, or other diseases and disorders related to or caused by cellular senescence in a mammal. The methods include administering one or more of the agents of the invention to a mammal, e.g., a human. The agents, which specifically bind to senescent cells, can be labeled with a radioactive label or a therapeutic label, e.g., a cytotoxic agent.</p>
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COMPOSITIONS OF ADENOSINE DEAMINASE-2 (ADA2), VARIANTS THEREOF AND METHODS OF USING SAME (Fri, 03 Aug 2018)
<p id="p-0001" num="0000">Provided are variant adenosine deaminase 2 (ADA2) proteins, conjugates thereof and compositions containing the proteins and/or conjugates. Also provided are methods and uses of the ADA2 proteins or conjugates for treating diseases and conditions, such as a tumor or cancer, and in particular any disease or condition associated with elevated adenosine or other associated marker.</p>
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TUMOR TARGETING CONJUGATES AND METHODS OF USE THEREOF (Fri, 03 Aug 2018)
Various compositions are disclosed. The compositions of conjugates comprising immune-stimulatory compounds are also provided. Additionally provided are the methods of preparation and use of the conjugates. This includes methods for treating disorders, such as cancer.
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SUBSTITUTED BICYCLIC PYRIMIDINE-BASED COMPOUNDS AND COMPOSITIONS AND USES THEREOF (Fri, 03 Aug 2018)
Novel C-2-substituted bicyclic compounds of Formula I have been prepared and found to be useful as potent inhibitors of hGGPPS by inhibiting geranylgeranylation of proteins and inhibiting the biosynthesis of GGPP. The application is directed to these compounds, to compositions comprising these compounds, and to their use, in particular as medicaments for use in the treatment of cancer and other conditions which are treatable by inhibiting human geranylgeranylation pyrophosphate hGGPPS activity.
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ALKOXY BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION (Fri, 03 Aug 2018)
The present invention relates to certain bis-heteroaryl compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer including melanoma.
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BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION (Fri, 03 Aug 2018)
The present invention relates to bis-heteroaryl compounds of formula (I), pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer including melanoma.
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BICYCLIC BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION (Fri, 03 Aug 2018)
The present invention relates to certain bicyclic bis-heteroaryl compounds of Formula (I), pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer including melanoma.
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NOVEL IGFR-LIKE 2 RECEPTOR AND USES THEREOF (Fri, 03 Aug 2018)
The present invention provides a novel IGFR-like receptor 2 and antagonists and agonists for targeting said receptor. Said antagonists and agonists are envisaged for use as a medicament, and in particular for treatment of cancer or diabetes.
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CALICHEAMICIN DERIVATIVES AND ANTIBODY DRUG CONJUGATES THEREOF (Fri, 03 Aug 2018)
The present invention is directed to novel calicheamicin derivatives useful as payloads in antibody-drug-conjugates (ADC's), and to payload-linker compounds and ADC compounds comprising the same; to pharmaceutical compositions comprising the same and to methods for using the same to treat pathological conditions such as cancer.
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1-(6-(3-HYDROXYNAPHTHALEN-1-YL)QUINAZOLIN-2-YL)AZETIDIN-1-YL)PROP-2-EN-1-ONE DERIVATIVES AND SIMILAR COMPOUNDS AS KRAS G12C INHIBITORS FOR THE TREATMENT OF CANCER (Fri, 03 Aug 2018)
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): (Formula (I)) or a pharmaceutically acceptable salt, stereoisomer thereof, wherein G, Y, R, R1, R2a, R2b, R2c, L, L1 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. Preferred compounds are quinazoline and quinazolinone derivatives and in particular 1-(6-(3-hydroxynaphthalen-1-yl)quinazolin-2-yl)azetidin-1-yl)prop-2-en-1-one derivatives and similar compounds.
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SYSTEMS AND METHODS FOR HEMATOPOIETIC CELL EXPANSION UTILIZING HYDROGELS (Fri, 03 Aug 2018)
Systems and methods to expand hematopoietic stem cell (HSC) using zwitterionic hydrogels (ZTG) are described. Expansion using the disclosed systems and methods results in HSC populations with (i) an increased proportion of HSC versus partially or fully differentiated cells, (ii) proportionally lower cell surface expression levels of differentiation/maturation markers, (iii) reduced metabolic rates following expansion, and/or (iv) a greater proportion of quiescent cells following expansion, as compared to currently available clinical expansion methods.
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PYRROLOPYRIMIDINE ITK INHIBITORS FOR TREATING INFLAMMATION AND CANCER (Fri, 03 Aug 2018)
Disclosed herein are arylpyridinone compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structure of Formula (I) wherein R1, R2, and X are as defined in the detailed description. Methods of inhibition of ITK activity in a human or animal subject are also provided.
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CD28 COMPOSITIONS AND METHODS FOR CHIMERIC ANTIGEN RECEPTOR THERAPY (Fri, 03 Aug 2018)
The invention provides compositions and methods for treating diseases associated with expression of a cancer associated antigen as described herein. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen as described herein, vectors encoding the same, and recombinant T cells comprising the CARs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a cancer associated antigen as described herein. The CAR may comprise a mutant CD28 costimulatory domain.
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THIENOPYRANONES AND FURANOPYRANONES AS KINASE, BROMODOMAIN, AND CHECKPOINT INHIBITORS (Fri, 03 Aug 2018)
The invention relates to compounds and methods of treating diseases including but not limited to, cancer, non-cancer proliferative disease, sepsis, autoimmune disease, viral infaction, atheroscleosis. Type 1 or 2 diabetes, obesity, inflammatory disease, or Myc-depenent disorder including by modulating biological processes by the inhibition of cell cycle checkpoint targets CDKs, and/or PI3 kinase, and/or bromodomain protein binding to substrates, comprising the administration of a compound(s) of Formula 1 -Vl (or pharmaceutically acceptable salts thereof) as defined herein.
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INHIBITORS OF HIV-1 INTEGRASE MULTIMERIZATION (Fri, 03 Aug 2018)
The disclosure generally relates to compounds of formulas (I) and (ll)7 including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV-1 integrase, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.
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METHODS OF TREATING CANCER (Fri, 03 Aug 2018)
Methods of regulating disorders and diseases by reducing tumor generated L-lactate in an environment surrounding a tumor, include administration of a fenoterol analogue, such as for example, MNF. The method may increase a cancer patient's response to an immune checkpoint blockade therapy.
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Inhibitors of histone demethylases (Fri, 03 Aug 2018)
Compounds of the form in which Q is selected from -CH=NR 12 , -W, -CH= 2NHR13 , -CH=O and -CH(OR 17 )2 capable of modulating the activity of histone demethylases (HDMEs), which are useful for prevention and/or treatment of diseases in which genomic dysregulation is involved in the pathogenesis, such as e.g. cancer and formulations and methods of use of such compounds.
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PIPERIDIN-4-YL AZETIDINE DERIVATIVES AS JAK1 INHIBITORS (Thu, 02 Aug 2018)
The present invention provides piperidin-4-yl azetidine derivative, shown below, (or the adipc acid salt thereof) which modulates the activity of Janus kinase 1 (JAK1) and is useful in the treatment of diseases related to the activity of JAK1 including, for example, inflammatory disorders, autoimmune disorders, cancer, and other diseases.
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MEANS AND METHODS FOR DIAGNOSING PANCREATIC CANCER IN A SUBJECT (Thu, 02 Aug 2018)
The present invention relates to the field of diagnostic methods. Specifically, the present invention contemplates a method for diagnosing pancreatic cancer in a subject, a method for identifying whether a subject is in need for a therapy of pancreatic cancer or a method for determining whether a pancreatic cancer therapy is successful. The invention also relates to tools for carrying out the aforementioned methods, such as diagnostic devices.
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ISOINDOLINE COMPOUNDS FOR USE IN THE TREATMENT OF CANCER (Thu, 02 Aug 2018)
Provided herein are isoindoline compounds of formula (III), pharmaceutical compositions comprising one or more of such compounds, and their use for treating, preventing, or managing various diseases, including cancer.
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Phenothiazine derivatives having CaM inhibitory activity (Wed, 01 Aug 2018)
<p id="p-0001" num="0000">The present invention provides a phenothiazine derivative or a pharmaceutically acceptable salt thereof, a method of preparing a compound selected therefrom and a pharmaceutical composition containing the compound as an active ingredient. The phenothiazine derivative according to the present invention has an effect of inhibiting calmodulin (CaM; calcium-modulated protein) and thus helps cell death by maintaining the intracellular level of calcium in lung cancer cells at high concentration. Accordingly, the phenothiazine derivative according to the present invention can be usefully used to prevent or treat malignant tumors such as lung cancer.</p>
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METHODS OF QUANTIFYING N2-(1-CARBOXYETHYL)-2'-DEOXY-GUANOSINE (CEDG) AND SYNTHESIS OF OLIGONUCLEOTIDES CONTAINING CEDG (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">Methods of quantifying N<sup>2</sup>-carboxyethyl-2′-deoxyguanosine (CEdG) levels in biological samples and comparing those levels to known normal levels can diagnose a number of disorders, including diabetes and cancer. Methods can also determine whether therapies for disorders are effective by measuring CEdG levels before and after treatment. Measurement of CEdG levels occurs using liquid chromatography electrospray ionization tandem mass spectrometry.</p>
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CERAMIDE DERIVATIVES AS ANTICANCER AGENTS (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">The invention provides a compound of formula (I): (I) wherein R<sup>1</sup>-R<sup>4 </sup>have any of the values defined in the specification, as well as compositions comprising a compound of formula (I) and methods for treating diseases (e.g. cancer).</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="62.74mm" file="US20180207123A1-20180726-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPOUNDS AND ANTI-TUMOR NQO1 SUBSTRATES (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">Compositions comprising Formula (I) can be selectively lethal toward a variety of different cancer cell types. The compositions are useful for the management, treatment, control, or adjunct treatment of diseases, where the selective lethality is beneficial in chemotherapeutic therapy.</p>
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Therapeutic Combinations of a BTK Inhibitor, a PI3K Inhibitor and/or a JAK-2 Inhibitor (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">Therapeutic combinations of a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms, are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of (1) a PI3K-δinhibitor and a BTK inhibitor, (2) a JAK-2 inhibitor and a BTK inhibitor, or (3) a JAK-2 inhibitor, PI3K-δ inhibitor, and BTK inhibitor, and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.</p>
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CRYSTALLINE FORM OF (S)-N-(5-((R)-2-(2,5-DIFLUOROPHENYL)-PYRROLIDIN-1-YL)-PYRAZOLO[1,5-A]PYRIMIDIN-3-YL)-3-HYDROXYPYRROLIDINE-1-CARBOXAMIDE HYDROGEN SULFATE (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">A novel crystalline form of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutical compositions containing said crystalline form and the use of said crystalline form in the treatment of pain, cancer, inflammation, neurodegenerative disease or <i>Trypanosoma cruzi </i>infection are disclosed. In some embodiments, the novel crystalline form comprises a stable polymorph of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate. The present invention is further directed to a process for the preparation of the novel crystalline form.</p>
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Methods and compositions for treating solid tumors and other malignancies (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">A combination of a CDK4/6 inhibitor and an mTOR inhibitor for the treatment of cancer.</p>
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POLYFLUORINATED COMPOUNDS ACTING AS BRUTON TYROSINE KINASE INHIBITORS (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">Described herein is a novel series of multi-fluoro-substituted pyrazolopyrimidine compounds or salts thereof. These compounds are Bruton's tyrosine kinase (BTK) inhibitors. These compounds may possess better BTK inhibition selectivity and pharmacokinetic properties. Disclosed herein are the synthesis methods of these compounds. Disclosed herein are novel synthesis methods of the multi-fluoro-substituted benzophenone and substituted phenoxy benzene. Also disclosed are pharmaceutical compositions comprising the BTK inhibitors described herein. The present invention also relates to pharmaceutical formulations comprising the compounds described herein as active ingredients. The present invention also includes the therapeutic methods by administering the BTK inhibitors and their formulations to treat and inhibit autoimmune disease, hypersensitivity disease, inflammatory diseases and cancer.</p>
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METHODS AND COMPOSITIONS USEFUL FOR TREATING DISEASES INVOLVING BCL-2 FAMILY PROTEINS WITH ISOQUINOLINE AND QUINOLINE DERIVATIVES (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">The present invention relates to a compositions for and methods for cancer treatment, for example, hematopoietic cancers (e.g. B-cell Lymphoma). In other aspects, the invention provides methods for treating particular types of hematopoietic cancers, such as B-cell lymphoma, using a combination of one or more of the disclosed compounds and, for example, 26S proteasome inhibitors, such as, for example, Bortezomib. In another aspect the present invention relates to autoimmune treatment with the disclosed compounds. In another aspect, this invention relates to methods for identifying compounds, for example, compounds of the BH3 mimic class, that have unique in vitro properties that predict in vivo efficacy against B-cell lymphoma tumors and other cancers as well as autoimmune disease.</p>
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ADMINISTRATION OF AURORA KINASE INHIBITOR AND CHEMOTHERAPEUTIC AGENTS (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">Disclosed are methods for the treatment of cancer in patients in need of such treatment. The methods comprise administering to such a patient an Aurora kinase inhibitor such as 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino}-2-methoxybenzoic acid or a pharmaceutically acceptable salt in combination with a platin. Also disclosed are medicaments for use in the treatment of cancer.</p>
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CARBAMATE COMPOUNDS AND METHODS OF MAKING AND USING SAME (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from indications such as pain, solid tumor cancer and/or obesity comprising administering a disclosed compound or composition.</p>
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Compounds and Methods of Use (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">This disclosure provides compounds and compositions and methods of using those compounds and compositions to treat diseases and disorders associated with excessive transforming growth factor-beta (TGFβ) activity. This disclosure also provides methods of using the compounds in combination with one or more cancer immunotherapies.</p>
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BICYCLIC HETEROCYCLIC DERIVATIVES AS MNK1 AND MNK2 MODULATORS AND USES THEREOF (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), inflammatory diseases, Alzheimer's disease), as well as methods of treating these diseases.</p>
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HETEROCYCLIC SPIRO COMPOUNDS AS MAGL INHIBITORS (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">The present invention provides, in part, heterocyclic spiro compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.70mm" wi="58.93mm" file="US20180208608A1-20180726-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating MAGL-mediated diseases and disorders including, e.g., pain, an inflammatory disorder, depression, anxiety, Alzheimer's disease, a metabolic disorder, stroke, or cancer.</p>
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NUCLEOTIDES FOR THE TREATMENT OF CANCER (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">The present application relates to novel nucleoside derivatives of formula (I) as claimed in claim <b>1,</b> pharmaceutical compositions comprising the compounds, processes of preparation thereof, and methods of use thereof for treating cancer.</p>
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3-(1H-PYRROLO[2,3-B]PYRIDIN-2-YL)-1H-INDAZOLES AND THERAPEUTIC USES THEREOF (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">Indazole compounds for treating various diseases and pathologies are disclosed. More particularly, the present disclosure concerns the use of an indazole compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, 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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Chelated PSMA Inhibitors (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">Compounds as defined herein are provided which are useful in (1) diagnostic methods for detecting and/or identifying cells presenting PSMA; (2) compositions comprising a compound of the invention together with a pharmaceutically acceptable diluent; and (3) methods for imaging prostate cancer cells.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.90mm" wi="72.73mm" file="US20180207298A1-20180726-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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INDENYL COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND MEDICAL USES THEREOF (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">Disclosed are compounds, for example, compounds of formula (I), (Formula (I) wherein R, R<sub>0</sub>, R<sub>1</sub>-R<sub>8</sub>, n, X, Y, Y′, and E are as described herein, pharmaceutical compositions containing such compounds, and methods of treating or preventing a disease or condition, for example, cancer.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.76mm" wi="59.52mm" file="US20180208573A1-20180726-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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ISOQUINOLIN-3-YL CARBOXAMIDES AND PREPARATION AND USE THEREOF (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">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.</p>
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2-ARYLAMINO PYRIDINE, PYRIMIDINE OR TRIAZINE DERIVATIVES, PREPARATION METHOD AND USE THEREOF (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">The present disclosure relates to 2-arylamino pyridine, pyrimidine, or triazine derivatives, and the preparation method and use thereof. The 2-arylamino pyridine, pyrimidine, or triazine derivatives may act on certain mutated forms of epidermal growth factor receptor, for example the L858R activating mutant, the delE746_A750 mutant, the Exon19 deletion activating mutant, and the T790M resistance mutant, so as to be used for treatment and prevention of diseases and medical conditions. The 2-arylamino pyridine, pyrimidine, or triazine derivatives may be used for treatment and prevention of cancer. The present disclosure also relates to a pharmaceutical composition comprising 2-arylamino pyridine, pyrimidine, or triazine derivatives, intermediates useful in the manufacture of 2-arylamino pyridine, pyrimidine, or triazine derivatives, and to methods of treatment of diseases mediated by various different forms of EGFR using 2-arylamino pyridine, pyrimidine, or triazine derivatives.</p>
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HTS Assay for Identifying Small Molecule Inhibitors of RAD52 and Uses of Identified Small Molecule Inhibitors for Treatment and Prevention of BRCA-Deficient Malignancies (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">Disclosed are methods, compositions, kits, and systems for identifying small-molecule drugs for treating cancer in a subject. The disclosed methods, compositions, kits, and systems may be utilized to identify small-molecule inhibitors of radiation sensitive protein 52 (RAD52) in order to treat cancer in a subject, such as breast cancer in a subject having a BRCA1-deficient, BRCA2-deficient, and/or PALB2-deficient phenotype by administering the identified small-molecule inhibitors to the subject.</p>
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HETEROCYCLIC COMPOUNDS AND USE THEREOF (Fri, 27 Jul 2018)
<p id="p-0001" num="0000">Heterocyclic compounds of Formula (I) shown herein. Also disclosed is a pharmaceutical composition containing one of the heterocyclic compounds. Further disclosed are methods of using one of the heterocyclic compounds for mobilizing hematopoietic stem cells and endothelial progenitor cells into the peripheral circulation, and for treating tissue injury, cancer, inflammatory disease, and autoimmune disease.</p>
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