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

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

Abstract: The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3,3-disubstituted-(8-aza-bicyclo[3.2.1]oct-8-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, 3,3-disubstituted-(6-aza-bicyclo[3.1.1]hept-6-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, and 4,4-disubstituted piperidin-1-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone compounds of the following formula that, inter alia, inhibit 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1).

Abstract: Certain compounds and pharmaceutically acceptable salts are provided herein. Also provided are pharmaceutical compositions comprising at least one compound or pharmaceutically acceptable salt therein and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain disease states responsive to the inhibition of transglutaminase TG2 activity are described. These disease states include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one compound or pharmaceutically acceptable salt thereof as a single active agent or administering at least one compound or pharmaceutically acceptable salt thereof in combination with one or more other therapeutic agents.

Abstract: Provided herein are compounds used to inhibit the deamination enzyme responsible for the inactivation of therapeutic compounds, and methods of using them.

Abstract: Compounds which directly inhibit IRE-1? activity in vitro, prodrugs, and pharmaceutically acceptable salts there-of. Such compounds and prodrugs are useful for treating diseases associated with the unfolded protein response or with regulated IRE1-dependent decay (RIDD) and can be used as single agents or in combination therapies.

Abstract: The present invention relates to compounds that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention. The invention further relates to processes for preparing these compounds.

Abstract: The present invention relates to compounds and methods which may be useful as inhibitors of phosphodiesterase 4 (PDE4) for the treatment or prevention of inflammatory diseases and other diseases involving elevated levels of cytokines and proinflammatory mediators.

Abstract: This invention relates to novel 2-{6-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-2-methyl-pyrimidin-4-ylamino}-thiazole-5-carboxylic acid (2-chloro-6-methyl-phenyl)-amide derivatives, and pharmaceutically acceptable acid addition salts thereof. The invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions beneficially treated by the inhibition of kinases including Src-kinase and Bcr-Abl kinase.

Abstract: Compounds represented by formula: Wherein X, Y and Z are as defined herein, pharmaceutically acceptable salts thereof, and related compounds, are suitable for use in treating or preventing a Flaviviridae viral infection in a host.

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: wherein the variables are as defined herein.

Abstract: Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I): where V, W, R1, R2, R3 and R4 are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.

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 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; solid forms 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-1: wherein the variables are as defined herein. Additionally, the compounds of this invention have formula II: or a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

Abstract: In accordance with certain embodiments of the present disclosure, a protein arginine methyltransferase inhibitor is provided. The inhibitor comprises an amino acid peptide joined to a chloroacetamidine warhead.

Abstract: The invention provides inhibitors of influenza endonuclease activity and tools for their discovery.

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: wherein the variables are as defined herein. Additionally, the present invention also relates to novel processes for the production of various morpoholine based intermediates.

Abstract: The present invention relates to antibodies including human antibodies and antigen-binding portions thereof that specifically bind to ErbB2, preferably human ErbB2. In another embodiment, the antibodies or antigen-binding portions thereof inhibit ErbB2. The invention also relates to antibodies that are chimeric, bispecific, derivatized, single chain antibodies or portions of fusion proteins. The invention also relates to isolated heavy and light chain immunoglobulins or portions thereof derived from human anti-ErbB2 antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of using the antibodies and compositions for diagnosis and treatment. The invention also provides gene therapy methods using nucleic acid molecules encoding the heavy and/or light immunoglobulin molecules that comprise the human anti-ErbB2 antibodies.

Abstract: Disclosed are compounds of formula I, compositions containing them, and methods of use for the compounds and compositions in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK 2 and JAK3, are therapeutically useful. Also disclosed are methods of making the compounds.

Abstract: Dipeptidyl peptidase IV (DPP-IV)-inhibiting compounds are provided that have formula I: wherein n is 1 to 3; X is CH2; S; O; CF2 or C(CH3)2; Z is H; halogen; hydroxyl; (C1-6)alkoxy; (C1-12)alkyl; (C3-12)cycloalkyl; phenyl; or heteroaryl; where the phenyl and heteroaryl groups are optionally mono- or independently plurisubstituted with R7; optionally, X together with an adjacent ring carbon and Z form a fused cyclopropyl; and optionally, one of the bonds in the ring containing X is a double bond; and CriRii, R1, R1, R3, R4 and R5 are as described herein. Methods for preparing these compounds, and methods for treating diabetes, especially Type II diabetes, and other related diseases are described using the compounds of formula I in pharmaceutical compositions which contain these compounds. Pharmaceutical compositions which contain combinations of these compounds with other antidiabetic agents are also described herein.

Abstract: The disclosure relates to a compound of formula (I): and salts thereof; wherein Ar, L, A, X, R1, R2, R3, R4a, R4b, and R5 are as defined in the disclosure; compositions comprising said compounds, methods for their preparation, intermediates thereto, and the use thereof, particularly as drugs.

Abstract: The invention provides methods for treating hepatitis C viral infections and related viral infections, as well as compounds and compositions that are useful for treating such infections.

Abstract: Inhibitors of the enzyme beta-lactamase are provided. The compounds are adapted to inhibit beta-lactamase as produced by beta-lactam resistant bacterial strains. Methods of treatment of beta-lactam resistant bacterial infections in patients are provided.

Abstract: Methods of treating an SCD-mediated disease or condition in a mammal, preferably a human, are disclosed, wherein the methods comprise administering to a mammal in need thereof a compound of formula (I): wherein W, V, x, y, R1, R2, R3, R4, R5, R6, R7, R7a, R8, R8a, R9, R9a, R10 and R10a are defined herein. Pharmaceutical compositions comprising the compounds of formula (I) are also disclosed.

Abstract: The present invention provides ?-hydroxy-?-aminophosphonates, ?-amino-?-aminophosphonates, and analogs thereof that inhibit carnitine acyltransferases. The invention also provides compositions comprising these ?-hydroxy-?-aminophosphonates, ?-amino-?-aminophosphonates, and analogs, and methods of the use of such compounds and compositions in the treatment, amelioration or prevention of pathological conditions, diseases or disorders that are linked with fatty acid metabolism, such as non-insulin dependent diabetes or obesity. The invention also provides processes for the preparation of such compounds and compositions.

Abstract: The present invention relates to an inhibitor of glycogen synthase kinase 3 (GSK-3) for use in a method of treating or preventing emphysema, a method of activating an emphysema cell, an activated emphysema cell obtained by this method for use in a method of treating or preventing emphysema, and a method of screening for a substance for treating or preventing emphysema.

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

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

Abstract: Compounds comprising an oligonucleotide moiety covalently linked to a lipid moiety are disclosed. The oligonucleotide moiety comprises a sequence that is complementary to the RNA component of human telomerase. The compounds inhibit telomerase activity in cells with a high potency and have superior cellular uptake characteristics.

Abstract: Described herein are novel beta-secretase inhibitors and methods for their use, including methods of treating Alzheimer's disease.

Abstract: Compounds that modulate, for example, that inhibit, syk kinase, and, optionally other kinases. The compounds can be used to treat a variety of disorders, including inflammatory disorders and autoimmune disorders.

Abstract: 4-(2,2-Difluoro-benzo[1,3]dioxol-5-ylmethyl)-piperazine-1-carboxylic acid (4-chloro-pyridin-3-yl)-amide is described, which is useful as a FAAH modulator. 4-(2,2-Difluoro-benzo[1,3]dioxol-5-ylmethyl)-piperazine-1-carboxylic acid (4-chloro-pyridin-3-yl)-amide may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity, such as anxiety, pain, inflammation, sleep disorders, eating disorders, energy metabolism disorders, and movement disorders (e.g., multiple sclerosis). A method of synthesizing 4-(2,2-difluoro-benzo[1,3]dioxol-5-ylmethyl)-piperazine-1-carboxylic acid (4-chloro-pyridin-3-yl)-amide is also disclosed.

Abstract: Disclosed are quinoline compounds having the formula: wherein R1, R2 and A are as defined herein, and methods of making and using the same.

Abstract: Provided are compounds of the formula (I): or a stereoisomer, tautomer, salt, hydrate or prodrug thereof that modulate tyrosine kinase activity, compositions comprising the compounds and methods of their use.

Abstract: Compounds which are sulfonamido 3,4-diarylpyrazole derivatives, or pharmaceutically acceptable salts thereof, their preparation process and pharmaceutical compositions comprising them are disclosed; these compounds are useful in the treatment of diseases caused by and/or associated with an altered protein kinase activity such as cancer, viral infection, prevention of AIDS development in HIV-infected individuals, cell proliferative disorders, autoimmune and neurodegenerative disorders; also disclosed is their use as prodrugs.

Abstract: Proteinopathies result from the proteasome not acting efficiently enough to eliminate harmful proteins and prevent the formation of the pathogenic aggregates. As described herein, inhibition of proteasome-associated deubiquitinase Usp 14 results in increased proteasome efficiency. The present invention therefore provides novel compositions and methods for inhibition of Usp14, enhancement of proteasome activity and treatment of proteinopathies.

Abstract: The present invention provides cyclohexyl azetidine derivatives, as well as their compositions and methods of use, that modulate 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 invention relates to new triazines (G=Q=U are N), pyrimidines (two out of G, Q and U are N), and pyridopyrimidines (one of G and U together with R2 forms an anullated pyridine ring) of formula (I) carrying a spirocyclic substituent, wherein E1 is CR4 or N; X1 is CHR4, CH2CH2, NR4, NR4?0, or O; and the other substituents are as defined in the specification. The compounds inhibit phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), DNA-PK and ATM kinase, and may be used as therapeutic agents or diagnostic probes. The invention also relates to methods of using the compounds for treatment of associated pathological conditions.

Abstract: A mechanism of monoamine oxidases (MAOs) driven epithelium-to-mesenchymal transition (EMT) is disclosed. Also disclosed are methods for treating cancer by inhibiting or suppressing MAOs in cancer cells. Novel MAOs inhibitors, such as small molecules, siRNA, shRNA, antisense oligonucleotides, aptamers, decoys, and pharmaceutical compositions useful for treating cancer by disrupting the workings of MAOs are provided. In particular, a class of conjugates formed by covalently conjugating near infrared dye 783, IR-780, and MHI-148 to a MAO inhibitor, such as clorgyline, with and without encapsulation it in a nanoparticle is provided. Other aspects of the invention include methods for forming the nano-conjugates, method for monitoring treatment progress in a cancer patient by monitoring the changes in MAO activity, methods for screening patients who are at risk of cancer or differentiating different forms of cancer by assaying the level and location of MAO activity.

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: Nitric oxide synthase (NOS) inhibitor compounds comprising bi-terminal aromatic ring moieties, and related methods of NOS inhibition.

Abstract: The present invention relates to human serine/threonine kinase ULK3 and its ability to regulate GLI transcription factors; mediators of SHH signaling. This disclosure demonstrates that ULK3 enhances endogenous and over-expressed GLI1 and GLI2 transcriptional activity in cultured cells, and ULK3 alters subcellular localization of GLI1. According to this disclosure ULK3 is an autophosphorylated kinase and phosphorylates GLI proteins in vitro. A peptide sequence in GLI1 C-terminus that is phosphorylated by ULK3 is provided in this disclosure. ULK3 catalytical activity is shown to be crucial for its function in SHH pathway. This disclosure shows that serine/threonine kinase ULK3 is involved in the SHH pathway as a positive regulator of GLI proteins. Furthermore, a therapeutic method in SHH dependent human disorders is disclosed by pharmacological inhibition of ULK3 kinase activity. Identification of ULK3 substrate sequence in GLI1 allows the design of peptide-based modulators of its kinase activity.

Abstract: A convenient and scalable synthesis of DGJNAc ID from D-glucuronolactone in an overall yield of 20% is provided. DGJNAc is the first highly potent and specific competitive inhibitor of GalNAcases. DGJNAc ID is also a competitive inhibitor of -hexosaminidases. Synthesis and activity of L-DGJNAc IL is also shown. The use of DGJNAc as a potent and specific inhibitor of GalNAcases will allow useful investigation and treatment of a number of diseases, including Schindler Disease.

Abstract: Described herein are compounds, pharmaceutical compositions and methods for the inhibition of RAF kinae mediated signaling. Said compounds, pharmaceutical compositions and methods have utility in the treatment of human disease and disorders.

Abstract: The present invention relates to methods for inhibiting subacute thrombosis and/or intimal hyperplasia following an interventional vascular procedure by contacting a blood vessel or a synthetic material with a mitogen-activated protein kinase (MAPK) pathway inhibitor. The present invention further relates to vascular devices comprising a MAPK pathway inhibitor.

Abstract: Methods of inhibiting kinases using kinase inhibitors having olefin moieties are disclosed.

Abstract: Heterocyclic entities that modulate PI3 kinase activity, pharmaceutical compositions containing the heterocyclic entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.

Abstract: Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of CNS disorders such as neuropsychiatric disorders.

Abstract: There are provided, inter alia, acyclic nucleoside phosphonate compounds having reduced toxicity and enhanced antiviral activity, and pharmaceutically accepted salts and solvates thereof. There are also provided methods of using the disclosed compounds for inhibiting viral RNA-dependent RNA polymerase, inhibiting viral reverse transcriptase, inhibiting replication of virus, including hepatitis C virus or a human retrovirus, and treating a subject infected with a virus, including hepatitis C virus or a human retrovirus.

Abstract: Pyridazinyl compounds, compositions and related methods of use.