Abstract: The present invention is directed to modulators of indoleamine 2,3-dioxygenase (IDO), as well as compositions and pharmaceutical methods thereof.

Abstract: Compounds that inhibit PI3K? activity, including compounds that selectively inhibit PI3K? activity, are disclosed. Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3K?) activity, and methods of treating diseases, such as disorders of immunity and inflammation in which PI3K? plays a role in leukocyte function, using the compounds also are disclosed.

Abstract: The invention provides compounds of the formula (0) or salts or tautomers or N-oxides or solvates thereof for use in the prophylaxis or treatment of disease states and conditions such as cancers mediated by cyclin-dependent kinase and glycogen synthase kinase-3. In formula (0): X is a group R1-A-NR4— or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO2, C?O, NRg(C?O) or O(C?O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g.

Abstract: A method for treating a neoplasm in a subject, comprising co-administering to the subject a therapeutically effective amount of an anticancer agent and a substituted 6,7-methylenedioxy-4-amino-quinoline, or a pharmaceutically acceptable salt or ester thereof.

Abstract: Compounds according to Formula I and Formula II are potent inhibitors of Arginase I and II activity: where R1, R2, R3, R4, R5, R6, R7, R8, R9, D, M, X, and Y are defined as set forth in the specification. The invention also provides pharmaceutical compositions of the compounds and methods of their use for treating or preventing a disease or a condition associated with arginase activity.

Abstract: The present invention relates to quinazolin-4-one compounds of formula (I?), their process of preparation and uses thereof. These compounds are useful as selective and reversible inhibitors of ubiquitin specific proteases, particularly USP7, for treating e.g. cancer, neurodegenerative diseases, inflammatory disorders and viral infections.

Abstract: The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. The compounds of this invention have formula I: or a pharmaceutically acceptable salt, wherein the variables are as defined herein.

Abstract: The present invention relates to dual delta (?) and gamma (?) PI3K protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of Pi3K kinase mediated diseases or disorders with them.

Abstract: The present disclosure relates to 2,4-pyrimidinediamines substituted with tricyclic carbamates and the compositions and methods using these compounds in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, such as JAK2 or JAK3, is therapeutically useful.

Abstract: This disclosure is directed to methods and compositions to inhibit MASP protein activity using small molecule inhibitors. In one aspect, the disclosure is directed to methods for identifying inhibitors of MASP protein activity, including methods of screening capable of inhibiting MASP protein activity.

Abstract: The present invention relates to compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising those compounds and methods of using the compounds and compositions in the treatment of various disease, conditions, and disorders. The invention also provides processes for preparing compounds of the invention.

Abstract: This invention relates to compounds that inhibit protein tyrosine kinase activity. In particular the invention relates to compounds that inhibit the protein tyrosine kinase activity of growth factor receptors, resulting in the inhibition of receptor signaling, for example, the inhibition of VEGF receptor signaling. The invention also provides compounds, compositions and methods for treating cell proliferative diseases and conditions and ophthalmic diseases, disorders and conditions.

Abstract: The invention relates to a new polynucleotide which encodes a polypeptide expressed in the salivary glands of ticks, more particularly the Ixodes ricinus arthropod tick, during the slow-feeding phase of the blood meal have, said polynucleotide and related polypeptide may be used in different constructions and for different applications which are also included in the present invention.

Abstract: The present invention relates to compounds that exhibit vasodilatory and anti-inflammatory effects by inhibiting the activity of soluble epoxide hydrolase (sEH). The present invention is also directed to methods of identifying such compounds, and use of such compounds for the treatment of diseases related to dysfunction of vasodilation, inflammation, and/or endothelial cells. In particular non-limiting embodiments, components of the invention may be used to treat hypertension.

Abstract: The present invention relates to novel neuraminidase activity inhibitors and use thereof for prophylaxis and treatment of influenza infection, that is to fluorosubstituted4-acetamido-5-guanidino-3-(pentan-3-yloxy)cyclohex-1-enecarboxylic acids and their esters of the general formula 1, pharmaceutically acceptable salts and/or hydrates thereof, wherein R is hydrogen, an optionally substituted C1-C5alkyl, C2-C5alkenyl or C2-C5alkynyl; Rf is CH2F or CHF2. A pharmaceutical composition is provided, a method for its preparation, as well as a method for prophylaxis and treatment of viral diseases.

Abstract: The present invention relates to kinase inhibiting compositions and uses thereof. The invention further provides isolated kinase inhibiting peptides and uses thereof for inhibiting hyperplasia, for inhibiting the growth of neoplasms, and for inducing programmed cell death in a cell population.

Abstract: The inventive compounds are small molecule therapeutics that are potent inhibitors of Arginase I and II activity. The invention also provides pharmaceutical compositions of the inventive compounds and methods for using the inventive compounds for treating or preventing a disease or a condition associated with arginase activity.

Abstract: Methods of inhibiting cytochrome P450 2D6 enzymes are provided that can be used for improving the treatment of diseases by preventing degradation of drugs or other molecules by cytochrome P450 2D6. Pharmaceutical compositions are provided that can act as boosters to improve the pharmacokinetics, enhance the bioavailability, and enhance the therapeutic effect of drugs that undergo in vivo degradation by cytochrome P450 2D6 enzymes.

Abstract: The present invention relates, for example, to a liposome, which can be a basic liposome, a transferrin-conjugated liposome, or a pH-sensitive liposome, which encapsulates a compound that specifically inhibits the activity of a protein prenyltransferase, such as a RabGGTase and/or a GGTase I. The liposomes can be used as anti-cancer therapeutics including as part of methods for treating cancer, in assays, and in kits.

Abstract: The present invention provides compounds of Formula I: or pharmaceutically acceptable salts thereof, as well as their compositions and methods of use, that inhibit the activity of Janus kinase (JAK) and are useful in the treatment of diseases related to the activity of JAK including, for example, inflammatory disorders, autoimmune disorders, cancer, and other diseases.

Abstract: The present invention provides active metabolites of 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl) -1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.

Abstract: The present invention relates to compounds useful as inhibitors of protein kinases, particularly of JAK family kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

Abstract: The present invention relates to compounds that exhibit vasodilatory and anti-inflammatory effects by inhibiting the activity of soluble epoxide hydrolase (sEH). The present invention is also directed to methods of identifying such compounds, and use of such compounds for the treatment of diseases related to dysfunction of vasodilation, inflammation, and/or endothelial cells. In particular non-limiting embodiments, components of the invention may be used to treat hypertension.

Abstract: The present invention is based on the seminal discovery that several kinases play important roles in barrier pathways in somatic cell reprogramming. The present invention provides that modulating expression or activity of these kinases can significantly promote or enhance cell reprogramming efficiency. Key kinases are identified and key regulation networks involving such kinases are also identified that may be advantageously targeted to significantly increase reprogramming efficiency as well as direct differentiation of induced pluripotent stem (iPS) cells.

Abstract: The present invention includes a crystal comprising a complex of the pro form of a matrix metalloprotease (proMMP) and a small-molecule allosteric processing inhibitor that inhibits that activation of the proMMP, methods for identifying small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP, and methods of treatment using small-molecule allosteric processing inhibitors that inhibit the activation of a proMMP. The present invention relates to the crystal structure of a complex of proMMP9 bound to a small-molecule allosteric processing inhibitor that inhibits activation of proMMP9. The invention further relates to the use of the methods and the crystal and related structural information for designing, selecting and/or optimizing small-molecule allosteric processing inhibitors that inhibit activation of proMMP9 and proMMP9 homologues.

Abstract: Inhibitors of saporin-L1 are disclosed, as are related compositions and uses thereof, in particular in cancer therapy that employs saporin-L1-linked immunotoxins.

Abstract: This disclosure concerns compounds which are useful as inhibitors of protein kinase C (PKC) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC. This disclosure also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

Abstract: The present embodiments provide for compositions and methods that regulate microRNA-binding protein-mediated miRNA biogensis; for example Lin28-mediated biogenesis of let-7; and in particular Lin28A-recruited 3? terminal uridylyl transferase (TUTase) uridylation of pre-let-7. A particular embodiment provide compositions and methods for screening for agents that inhibit TUTase-dependent Lin28A-mediated repression of let-7 miRNA.

Abstract: Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

Abstract: The invention provides novel guanylate cyclase-C agonist peptides and their use in the treatment of human diseases including gastrointestinal disorders, inflammation or cancer (e.g., a gastrointestinal cancer). The peptides can be administered either alone or in combination with an inhibitor of cGMP-dependent phosphodiesterase. The gastrointestinal disorder may be classified as either irritable bowel syndrome, constipation, or excessive acidity etc. The gastrointestinal disease may be classified as either inflammatory bowel disease or other GI condition, including Crohn's disease and ulcerative colitis, and cancer.

Abstract: The invention is directed to compounds of Formula I: wherein Z, X, J, R2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase. Methods of treating autoimmune diseases; and diseases with an inflammatory component; treating metastasis from ovarian cancer, uterine cancer, breast cancer, prostate cancer, lung cancer, colon cancer, stomach cancer, hairy cell leukemia; and treating pain, including skeletal pain caused by tumor metastasis or osteoarthritis, or visceral, inflammatory, and neurogenic pain; as well as osteoporosis, Paget's disease, and other diseases in which bone resorption mediates morbidity including rheumatoid arthritis, and other forms of inflammatory arthritis, osteoarthritis, prosthesis failure, osteolytic sarcoma, myeloma, and tumor metastasis to bone with the compounds of Formula I, are also provided.

Abstract: The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Abstract: Provided are pyrimidine compounds for inhibiting of Syk kinase, intermediates used in making such compounds, methods for their preparation, pharmaceutical compositions thereof, methods for inhibition Syk kinase activity, and methods for treating conditions mediated at least in part by Syk kinase activity.

Abstract: This invention relates to, among other items, benzoxaborole compounds and their use for treating bacterial infections.

Abstract: The present invention relates to compounds useful as inhibitors of protein kinases, particularly of JAK family kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

Abstract: Provided herein are methods for treating or preventing chronic lymphocytic leukemia, comprising administering an effective amount of a Dihydropyrazino-Pyrazine Compound to a patient having chronic lymphocytic leukemia.

Abstract: Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds described herein are useful for inhibiting arginine methyltransferase activity. Methods of using the compounds for treating arginine methyltransferase-mediated disorders are also described.

Abstract: Provided herein are methods for treating or preventing glioblastoma multiforme (GBM) characterized by O6-methylguanine-DNA methyltransferase (MGMT) expression and/or promoter methylation status, comprising administering an effective amount of a Dihydropyrazino-Pyrazine Compound to a patient having glioblastoma multiforme (GBM) characterized by O6-methylguanine-DNA methyltransferase (MGMT) expression and/or promoter methylation status.

Abstract: Provided herein are methods for treating or preventing head and neck squamous cell carcinoma characterized by deletion of chromosome 11q22 or loss of ataxia telangiectasia mutated expression, comprising administering an effective amount of a dihydropyrazino-pyrazine to a patient having head and neck squamous cell carcinoma characterized by deletion of chromosome 11q22 or loss of ataxia telangiectasia mutated expression.

Abstract: We describe a nucleic acid comprising the sequence RNNWCAAA, in which R is independently G or A, N is independently T, C, G or A and W is independently T or A, suitable for the treatment or prevention of hepatitis B or cancer. N at position 3 may be C, A or T, preferably A or T, more preferably T; N at position 2 may be C; W at position 4 may be T; and R at position 1 may be A. The nucleic acid may have the sequence ACATCAAA or ACTTCAAA.

Abstract: The present invention provides compounds useful as inhibitors of Btk, compositions thereof, and methods of using the same.

Abstract: Provided are pyrazine compounds for inhibiting of Syk kinase, intermediates used in making such compounds, methods for their preparation, pharmaceutical compositions thereof, methods for inhibition Syk kinase activity, and methods for treating conditions mediated at least in part by Syk kinase activity.

Abstract: The present invention relates to compounds of Formula I: as well as pharmaceutically acceptable salts, hydrates, isomers, or solvates thereof, wherein the variables are described herein. The present invention further relates to pharmaceutical compositions which comprise the compounds of Formula I, and to methods for inhibiting protein kinase and methods of treating diseases, such as cancers, inflammation.

Abstract: Compounds having methyltransferase inhibitory activity are disclosed. The compounds have the structure and are useful in the treatment of cancer and similar diseases associated with inappropriate methyltransferase activity.

Abstract: The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Abstract: The present disclosure provides methods of reducing immunodeficiency virus transcription, involving use of diflunisal or an active ester thereof. The disclosure also provides methods of treating an immunodeficiency virus infection in an individual, the method generally involving administering to the individual an effective amount of diflunisal or an active ester thereof.

Abstract: This invention relates to compounds that inhibit E1 activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia.

Abstract: The present invention is directed to methods and compositions for suppressing lymphangiogenesis, angiogenesis and/or tumor growth. The methods comprise contacting the tumor with a compound that (i) stabilizes a protein kinase in the inactive state and (ii) is not an ATP competitive inhibitor of the protein kinase in the active state.

Abstract: The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Abstract: The invention provides methods for inducing, enhancing or increasing satellite cell proliferation, and an assay for screening for a candidate compound for inducing, enhancing or increasing satellite cell proliferation. Also provided is a method for repairing or regenerating a damaged muscle tissue of a subject.