Abstract: The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated TRK kinase activity.

Abstract: The present invention provides 2,4-pyrimidinediamine compounds that inhibit the IgE and/or IgG receptor signaling cascades that lead to the release of chemical mediators, intermediates and methods of synthesizing the compounds and methods of using the compounds in a variety of contexts, including in the treatment and prevention of diseases characterized by, caused by or associated with the release of chemical mediators via degranulation and other processes effected by activation of the IgE and/or IgG receptor signaling cascades.

Abstract: Thiazolylphenyl-benzenesulfonamido derivatives of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.

Abstract: The invention provides pyrazolyl guanidine compounds that inhibit F1Fo-ATPase, and methods of using pyrazolyl guanidine compounds as therapeutic agents to treat medical disorders, such as an immune disorder, inflammatory condition, or cancer.

Abstract: A composition for preventing or treating inflammatory arthritis wherein the composition comprises an innate defence regulatory peptide named IDR-1002, said peptide comprising an amino acid sequence listing of VQRWLIVWRIRK, and/or a derivative thereof and/or an analog thereof. Use of the IDR-1002 peptide and/or a derivative thereof and/or an analog or a composition comprising the peptide and/or a derivative and/or analog to modulate the expression and/or function of an inflammatory cytokine and/or a matrix metallopeptidase-3 and/or a cell-signalling pathway.

Abstract: This invention relates to generally inhibiting histone deacetylase (“HDAC”) enzymes (e.g., HDAC1, HDAC2, and HDAC3).

Abstract: The present invention relates to compounds of formula I: or a pharmaceutically acceptable salts thereof 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 useful as antiviral agents. The invention further relates to pharmaceutically acceptable compositions comprising said compounds either for ex vivo use or for administration to a patient suffering from HCV infection and to processes for preparing the compounds. The invention also relates to methods of treating an HCV infection in a patient by administering a pharmaceutical composition comprising a compound of this invention.

Abstract: Provided is a plant derived extract including inhibitory activity against one or more extracellular proteases which degrade human tissue matrix. Moreover, the amount of inhibitory activity in an extract can be increased by stressing the plant prior to forming an extract. These extracts are each prepared by a process and demonstrate the ability to inhibit one or more extracellular proteases which degrade human tissue matrix. Libraries of extracts can be prepared from stressed and non-stressed plants, where each of the extracts demonstrate inhibitory activity against on or more extracellular protease inhibitors. Alternatively, semi-purified and purified inhibitory compounds can be isolated from the extracts.

Abstract: The present invention is directed to compounds of formula (I) and tautomers thereof or pharmaceutically acceptable salts, esters, and prodrugs thereof which arc inhibitor of Syk kinase. The present invention is also directed to intermediates used in making such compounds, the preparation of such a compound, pharmaceutical compositions containing such a compound, methods of inhibition Syk kinase activity, methods of inhibition the platelet aggregation, and methods to prevent or treat a number of conditions mediated at least in part by Syk kinase activity, such as undesired thrombosis and Non Hodgkin's Lymphoma.

Abstract: According to the embodiments described herein, a SUMOylation inhibitor compound comprising a singleton scaffold is provided. In some embodiments, a method for inhibiting a SUMOylation enzyme in a cell is provided. Such a method may include administering a SUMOylation inhibitor compound to the cell. In some aspects, the SUMOylation enzyme is SUMO E1 or SUMO E2. In some aspects, the method may be used to inhibit a cancer cell in vitro (e.g., grown in culture) or in vivo (e.g., as part of a tumor in a subject). In other embodiments, a method for treating a cancer, degenerative diseases and viral infection is provided. Such a method may include administering an effective amount of a pharmaceutical composition to a subject having the cancer. The pharmaceutical composition may include a singleton SUMOylation inhibitor compound.

Abstract: Novel compounds of formula 1 or a pharmaceutically acceptable salt thereof inhibit cytochrome P450 monooxygenase.

Abstract: The present invention relates to methods of modulating (for example, inhibiting) activity of JAK3, comprising contacting the JAK3 with a compound of Formula I: or pharmaceutically acceptable salt thereof, wherein constituent members are provided hereinwith. The present invention further provides novel compounds and compositions as well as their methods of preparation and use of the same as JAK3 inhibitors in the treatment of JAK3-associated diseases including, for example, inflammatory and autoimmune disorders.

Abstract: The present invention discloses a compound separated from Monascus-fermented rice, the preparation method and uses thereof. Specifically, the present invention discloses a compound represented by the Formula I, or a pharmaceutically acceptable salt thereof, wherein, R1 is selected from the group consisting of hydrogen, hydroxyl, C1-6 straight or branched alkoxyl, (II), (III) and (IV); R2 is hydrogen or C1-6 alkyl; R3 is selected from the group consisting of hydrogen, hydroxyl and C1-6 straight or branched alkoxyl. The present invention further discloses a pharmaceutical composition containing the compound. The compound of the present invention has HMG-CoA reductase inhibition effects.

Abstract: Novel peptide inhibitors of GSK-3, compositions containing same and uses thereof are disclosed. The novel peptide inhibitors are substrate-competitive inhibitors and have an amino acid sequence designed so as to bind to a defined binding site subunit in GSK-3. Also disclosed are GSK-3 substrate competitive inhibitors which bind to the defined binding site subunit in the enzyme. Also disclosed are mutants of GSK-3 and uses thereof for identifying a putative GSK-3 substrate competitive inhibitor.

Abstract: The present invention relates to novel acridine derivatives of formula (I), or pharmaceutically acceptable salts thereof, which are inhibitors of the telomerase enzyme function. These compounds are useful for the treatment cellular proliferation disorders, such as cancer.

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

Abstract: The present invention is directed towards methods of culturing non-keratinocyte epithelial cells, with the methods comprising culturing non-keratinocyte epithelial cells in the presence of feeder cells and a calcium-containing medium while inhibiting the activity of Rho kinase (ROCK) in the feeder cell, the non-keratinocyte epithelial cells or both during culturing.

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.

Abstract: Novel peptide inhibitors of GSK-3, compositions containing same and uses thereof are disclosed. The novel peptide inhibitors are substrate-competitive inhibitors and have an amino acid sequence designed so as to bind to a defined binding site subunit in GSK-3.

Abstract: The invention provides a method of inhibiting the catalytic activity of a protein kinase comprising contacting said protein kinase with a compound of formula (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing the same, and also provides a method of treating a protein kinase related disorder comprising a step of administering to a patient in need thereof a therapeutically effective amount of the compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing the same, wherein each substituent in formula (I) is same as defined in the description.

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 a novel use of naturally occurring plants, mushroom, extracts thereof that exhibit properties as HCV NS5B polymerase inhibitors.

Abstract: Small molecule inhibitors of bacterial ribonuclease (e.g., RnpA) and methods for their synthesis and use are described herein. The methods of using the compounds include treating and preventing microbial infections and inhibiting bacterial ribonuclease. Also described herein are methods of identifying compounds for treating or preventing a microbial infection.

Abstract: Compounds and pharmaceutical compositions are provided that inhibit the activity of poly ADP-ribose synthetase (PARP). Such compounds are useful in the treatment of various diseases, conditions and injuries such as stroke, myocardial infarction, ischemia-perfusion injury in various organs, traumatic brain injury, atherosclerosis, inflammatory diseases and cancer.

Abstract: The present invention relates to [1,2,4]triazolo[1,5-c]pyrimidine derivatives of formula (I) which inhibit the activity of Heat Shock Protein Hsp90. The compounds of the invention are therefore useful in treating proliferative diseases such as cancer and neurodegenerative diseases. The present invention also provides processes for preparing these compounds, methods of treating diseases and the pharmaceutical compositions comprising these compounds.

Abstract: Compounds of formula (I) in which R3 is chosen from hydrogen, cyano, nitro, acetyl and C(?O)NH2, and Ar is optionally substituted monocyclic or bicyclic aryl or heteroaryl, are useful as antitumor agents.

Abstract: Small molecule inhibitors of bacterial ribonuclease (e.g., RnpA) and methods for their synthesis and use are described herein. The methods of using the compounds include treating and preventing microbial infections and inhibiting bacterial ribonuclease.

Abstract: The invention relates to substituted imidazo- and triazolopyrimidines, imidazo- and pyrazolopyrazines and imidazotriazines and processes for their preparation, and their use for the manufacture of medicaments for the treatment and/or prophylaxis of diseases, in particular of hematological disorders, preferably of leukopenias and neutropenias.

Abstract: The invention provides a compound of formula (I): or a salt thereof, wherein R1-R4 have any of the values described in the specification, as well as compositions comprising a compound of formula (I). The compounds are useful as antibacterial agents.

Abstract: The present invention relates to tricyclic pyrrolo derivatives of Formula (I), which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing such these compounds or the pharmaceutical compositions containing them.

Abstract: Targeting metabolic enzymes in human cancer Abstract Lung cancer is a devastating disease and a major therapeutic burden with poor prognosis. The functional heterogeneity of lung cancer (different tumor formation ability in bulk of tumor) is highly related with clinical chemoresistance and relapse. Here we find that, glycine dehydrogenase (GLDC), one of the metabolic enzyme involved in glycine metabolism, is overexpressed in various subtypes of human lung cancer and possibly several other types of cancers. GLDC was found to be highly expressed in tumor-initiating subpopulation of human lung cancer cells compared with non-tumorigenic subpopulation. By array studies we showed that normal lung cells express low levels of GLDC compared to xenograft and primary tumor. Functional studies showed that RNAi inhibition of GLDC inhibits significantly the clonal growth of tumor-initiating cells in vitro and tumor formation in immunodeficient mice.

Abstract: Provided herein are pyrimidinyl and 1,3,5-triazinyl benzimidazole sulfonamides, e.g., compounds of Formulae IA, IB, and IC, and their pharmaceutical compositions, preparation, and use as agents or drugs for cancer therapy, either alone or in combination with radiation and/or other anticancer drugs.

Abstract: Compositions and methods are provided for preventing or attenuating cancer progression or blocking metastasis in prostate cancer and other cancers (e.g., ovarian carcinoma, endometrial cancer, renal cell carcinoma) that are characterized by overexpression of the type II cell surface serine protease hepsin, based on the discovery of multiple disclosed compounds having activity as specific hepsin inhibitors.

Abstract: The present invention relates to uses of agents that inhibit Jun kinases and/or FOXO4 in treating cancer and/or removing senescent cells in an individual.

Abstract: Isoxazoles of formula (A) or (B) are inhibitors of HSP90 activity, and useful for treatment of, for example cancers: wherein R1, is a group of formula (IA): —Ar1-(Alk1)p-(Z)r-(Alk2)s-Q, wherein in any compatible combination Ar1 is an optionally substituted aryl or heteroaryl radical, Alk1 and Alk2 are optionally substituted divalent C1-C6 alkylene or C2-C6 alkenylene radicals, p, r and s are independently 0 or 1, Z is -0-, —S—, —(C?O)—, —(C?S)—, —SO.sub.

Abstract: The invention provides a compound of formula (I): or a salt thereof, wherein R1-R5 have any of the values described in the specification, as well as compositions comprising a compound of formula (I). The compounds are useful as RNA polymerase inhibitors and antibacterial agents.

Abstract: This invention provides, among other things, novel compounds useful for treating inflammatory conditions, pharmaceutical compositions containing such compounds, as well as combinations of these compounds with at least one additional therapeutically effective agent.

Abstract: Provided herein are compounds and methods of using same for the perturbation and/or inhibition of protein-protein interactions. Also provided herein is a data mining method useful for the identification of protein-protein interactions that may be inhibited by these compounds.

Abstract: The present invention is directed to dihydrochloric acid and dibenzenesulfonic acid salts of the c-Met kinase inhibitor 2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)-imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide, and pharmaceutical compositions thereof, useful in the treatment of cancer and other diseases related to the dysregulation of kinase pathways. The present invention further relates to processes and intermediates for preparing 2-fluoro-N-methyl-4-[7-(quinolin-6-ylmethyl)imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide, and salts thereof.

Abstract: Disclosed herein are compounds of formula (I) and methods of inhibiting IKK? and the NF-?B signaling and mTOR pathways.

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: Compounds of formula (I) modulate JNK wherein X1 and X2 are each simultaneously N or CH; X3 is CH—R2 Or N—SO2R, where R is lower alkyl; R1 is aryl or heteroaryl, substituted with 0-3 lower alkyl radicals; R2 is (II), where R3 is H, lower acyl, or an amino acid, or a pharmaceutically acceptable salt thereof.

Abstract: Serine hydrolases are implicated in malconditions such as cancer, central nervous system disorders, cardiovascular disorders, obesity, and metabolic disorders. Many serine hydrolases expressed in proteomic libraries are of unknown function in vivo. Compounds identified through library versus library screening can be used for treatment of malconditions associated with the specific serine hydrolase KIAA1363 (also known as AADACL1). A library of inhibitors of KIAA1363 was prepared and candidate compounds were identified as a potent inhibitors having submicromolar IC50 values. An exemplary compound of the invention was shown to be an effective inhibitor of prostate cancer pathogenesis. Other inhibitory compounds of the invention comprising fluorophore groups are shown to be effective in spatial and temporal localization of the serine hydrolase in cells and tissues.

Abstract: The present invention relates to compounds useful as inhibitors of choline kinase. 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. The invention also provides processes for preparing compounds of the inventions.

Abstract: The invention provides a peptide comprising or consisting of SEQ ID NO: 1 and variants thereof, particularly comprising of consisting of the sequence FTY, nucleic acids encoding said peptides and pharmaceutical and nutraceutical compositions comprising said peptide(s) and/or nucleic acids. Also provided is the use of such a peptide in therapy and in vitro methods of ACE-inhibition.

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: Topoisomerase II alpha (topo II?) is exported from the cell nucleus in human myeloma cells by a chromosome-maintenance protein-1 (CRM1)-dependent mechanism, resulting in topo II inhibitor resistance. The nuclear export signal (NES) of topo II? is unique, making it a potential target for small molecule inhibitors. Small molecules NES inhibitors were identified, which inhibited binding of topo II? to the export receptor CRM1. Inhibition was specific to topo II? as p53 trafficking was unaffected along with topo II? protein expression and function (decatenation). These topo II?-specific nuclear export inhibitors may potentially lead to a new approach in circumventing drug resistance in multiple myeloma. The compounds provide a protocol for treating multiple myeloma or an oncogenic disease. Further, the topoisomerase II nuclear export signal inhibitor may be combined with a topoisomerase II inhibitor.

Abstract: The invention provides inhibitors of focal adhesion kinase, an enzyme involved in the attachment of the cytoskeleton of a cell to an extracellular matrix, which has been implicated in processes such as cell migration, cell proliferation, and cell survival. The inhibitors are derivatives of a 5-substituted 2,4-diaminopyridine wherein the substituents are as defined herein. The invention also provides a method of using the inhibitors in treatment of cancer, and methods of preparation of the inhibitors by use of coupling reactions.

Abstract: The invention relates to a novel class of 2,4-diamino-6,7-dihydro-5H-pyrrolo[2,3]pyrimidine derivatives as a FAK and/or Pyk2 inhibitor, to a process for their preparation, and to a composition thereof, as well as to use of the compounds for the inhibiting FAK and/or Pyk2 and method for the treatment of a FAK and/or Pyk2 mediated disorder or disease.

Abstract: Provided herein are conformationally stabilized ubiquitin proteins and methods for using the same to identify agents that bind to the stabilized ubiquitin protein or that bind to a protein that interacts with or processes the stabilized form of the ubiquitin protein. Also provided herein are methods for screening for conformationally stabilized proteins having increased binding affinity to a binding partner in comparison to the binding affinity of the wildtype form of the protein to the binding partner.