Abstract: The invention provides substrate specificity profiles for serine protease prostasin. Optimal prostasin substrate sequences, both to the prime side and non-prime side of the prostasin recognition site, are disclosed herein. The prostasin substrate sequences are used in designing substrates, inhibitors, and prodrugs. Prostasin inhibitors based on substrate specificity are also provided.

Abstract: The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of the Abl, BCR-Abl, Bmx, c-Raf, Csk, Fes, FGFR, Flt3, Ikk, IR, JNK, Lck, Mkk, PKC, PKD, Rsk, SAPK, Syk, Trk, BTK, Src, EGFR, IGF, Mek, Ros and Tie2 kinases.

Abstract: Methods and/or systems for modeling molecular systems and/or other physical systems using scaling optimization.

Abstract: The invention provides general methods for preparing 2,9-, 2,6,9-, O6-aryl- and O6-alkyl-substituted purines in a combinatorial and traceless fashion. The methods involve, in some embodiments, Mitsunobu alkylation of 2-fluoro-6-phenylsulfenylpurine at N9 with alcohols in solution, followed by C2-capture of the purine core with a resin-bound amine and subsequent oxidation and displacement of the C6 sulfonyl group with amines and anilines. In one aspect, the present invention provides a method of preparing a 2,6,9-substituded purine compounds of Formula I: the method comprising: a) oxidizing a resin-bound compound of Formula II: to provide a resin-bound compound of Formula III: b) reacting the compound of Formula III with an amine of Formula IV NR3R4??IV, to provide a resin-bound compound of Formula V c) cleaving the resin-bound compound of Formula V from the resin to provide the substituted purine compounds of Formula I.

Abstract: The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of the Abl, BCR-Abl, PDGF-R, lck, SAPK2?, p38, TGF?, KDR, c-Kit, b-RAF, c-RAF, FLT1 and FLT4 kinases.

Abstract: The present invention provides methods of identifying circadian rhythm modulators and methods of modulating circadian rhythm in animals.

Abstract: The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of the Abl, BCR-Abl, CSK, JNK1, JNK2, PDGF-R, p38, p70S6K, TGF?, SRC, EGFR, c-Kit, trkB, FGFR3, Fes, Lck, Syk, RAF, MKK4, MKK6 and SAPK2? kinases.

Abstract: The present invention provides grasping mechanisms, gripper apparatus/systems, and related methods. Grasping mechanisms that include stops, support surfaces, and height adjusting surfaces to determine three translational axis positions of a grasped object are provided. In addition, grasping mechanisms that are resiliently coupled to other gripper apparatus components are also provided.

Abstract: The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of the Abl, BCR-Abl, EGF-R, c-erbB2 kinase (HER-2), CHK2, FGFR3, p70S6K, PKC, PDGF-R, p38, TGF?, KDR, c-Kit, b-RAF, c-RAF, FLT1 and/or FLT4 kinases.

Abstract: This invention provides material conveying systems that are configured to convey substantially uniform quantities of material to and/or from the material sites and to minimize periodic variation among the conveyed quantities of material. Related computer program products and methods are also provided.

Abstract: The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of the Abl, BCR-Abl, Bmx, CSK, TrkB, FGFR3, Fes, Lck, B-RAF, C-RAF, MKK6, SAPK2? and SAPK2? kinases.

Abstract: The present invention provides universal G protein-coupled receptor (GPCR) reporter constructs. The constructs comprise a serum response element, a cAMP response element, and a multiple response element. These reporter constructs are able to detect activities of all GPCRs examined. Further provided by the present invention are host cells harboring a universal GPCR reporter construct of the invention, as well as assays for detecting modulators of GPCRs using the host cells.

Abstract: The present invention provides, inter alia, fluorogenic enzyme substrates, such as fluorogenic polypeptide substrates, libraries of fluorogenic enzyme substrates and methods for assaying for enzymatically active enzymes, such as hydrolases (e.g., proteases), in biological samples.

Abstract: The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases and disorders associated with kinase activity, particularly diseases associated with the activity of CDK1, CDK2, CDK4, CDK5, GSK3?, Bcr-ab1, Flt-3, c-Kit, PDGFR?, Src, Mek1 and CK1.

Abstract: The present invention provides a transgenic non-human animals comprising a disruption in the melanopsin gene as well as methods for using the animals to identify agents useful for modulating circadian rhythm in animals.

Abstract: This invention describes gene targets for the development of therapeutics to treat drug addiction. Animal models of drug craving and relapse have been developed and used to find gene expression changes in key brain regions implicated in cocaine addiction. The genes whose expression levels are altered serve as pharmacological targets with the purpose of preventing or inhibiting cocaine craving and relapse in human cocaine addicts.

Abstract: The present invention provides compounds, compositions and methods for the selective inhibition of cathepsin S. In a preferred aspect, cathepsin S is selectively inhibited in the presence of at least one other cathepsin isozyme. The present invention also provides methods for treating a disease state in a subject by selectively inhibiting cathepsin S.

Abstract: This invention provides novel methods for synthesis of narrow polydispersity oxazolone-containing polymers via nitroxide-mediated living free radical polymerization, as well as the products and derivatives thereof.

Abstract: The present invention provides, compounds, methods and compositions of biologically important indoles. In addition, the present invention provides synthesis methods for substituting leaving groups at positions 4 and 7 of the indole ring as diversity generating elements.

Abstract: The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with cSRC, Lck, FGFR3, Flt3, TrkB, Bmx, and/or PFGFR? kinase activity.