Abstract: Human PSMC genes are identified as modulators of the RB pathway, and thus are therapeutic targets for disorders associated with defective RB function. Methods for identifying modulators of RB, comprising screening for agents that modulate the activity of PSMC are provided.

Abstract: A compound according to Formula I: or a pharmaceutically acceptable salt thereof, wherein R1, R2, R11, L1 and X are as defined in the specification, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: Human MARK genes are identified as modulators of the p53 pathway, and thus are therapeutic targets for disorders associated with defective p53 function. Methods for identifying modulators of p53, comprising screening for agents that modulate the activity of MARK are provided.

Abstract: Disclosed are methods of treating cancer by administering a compound of Formula I, or a pharmaceutically acceptable salt thereof, in combination with gemcitabine (GEM), or a pharmaceutically acceptable salt thereof, and optionally one or more additional treatments, wherein: R1 is halo; R2 is halo; R3 is (C1-C6)alkyl; R4 is (C1-C6)alkyl; and Q is CH or N.

Abstract: Compounds, pharmaceutical compositions and methods for modulating the activity of nuclear receptors are provided. In particular, quinazolinones are provided for modulating the activity of farnesoid X receptor (FXR) and/or orphan nuclear receptors.

Abstract: Compounds, compositions and methods for modulating the activity of receptors are provided. In particular compounds and compositions are provided for modulating the activity of receptors and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder directly or indirectly related to the activity of the receptors.

Abstract: Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N?-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N?-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N?-(4-ffluorophenyl)cyclopropane-1,1-dicarboxamide.

Abstract: Human MYLK genes are identified as modulators of branching morphogenesis, and thus are therapeutic targets for disorders associated with defective branching morphogenesis function. Methods for identifying modulators of branching morphogenesis, comprising screening for agents that modulate the activity of MYLK are provided.

Abstract: The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. More specifically, the invention provides quinazolines and quinolines which inhibit, regulate, and/or modulate kinase receptor, particularly c-Met, KDF, c-Kit, flt-3 and flt-4, signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. The present invention also provides methods for making compounds as mentioned above, and compositions which contain these compounds.

Abstract: A compound having Formula (I) or a pharmaceutically acceptable salt thereof, wherein X, R1 and R2 are defined in the specification; pharmaceutical compositions thereof; and methods of use thereof.

Abstract: The invention is directed to Compounds of Formula I: optionally as a single stereoisomer or mixture of stereoisomers thereof, and additionally optionally as a pharmaceutically acceptable salt thereof; as well as methods of making and using the compounds.

Abstract: This invention relates to the field of protein tyrosine kinases and inhibitors thereof. In particular, the invention relates to inhibitors of JAK-2, pharmaceutical compositions of the compounds for inhibiting JAK-2, methods of inhibiting JAK-2 in a cell, comprising contacting a cell in which inhibition of JAK-2 is desired with a compound or pharmaceutical composition comprising a compound according to the invention. The also comprises methods of treating a disease or condition that involves JAK-2 comprising administering to a patient a pharmaceutical composition comprising a compound according to the invention.

Abstract: The present invention relates to compounds of the Formula (I) and (II) wherein R, R21, R25-R33, m, n, X21-X23, and Q1 are defined herein. The compounds modulate protein kinase enzymatic activity to modulate cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinases, particularly p70S6 and/or Akt kinases. Methods of using and preparing the compounds, and pharmaceutical compositions thereof, to treat kinase-dependent diseases and conditions are also an aspect of the invention.

Abstract: Compounds, compositions and methods for modulating the activity of receptors are provided. In particular compounds and compositions are provided for modulating the activity of receptors and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder directly or indirectly related to the activity of the receptors.

Abstract: This invention is based on the discovery that the administration of a sphingosine-1-phosphate receptor antagonist (S1P) and at least one chemotherapeutic agent selected from the the group of antimicrotubule agents provides an unexpectedly superior treatment for cancer. Antimicrobial agents such as the taxane compounds are known in the art, for example, paclitaxel (available as TAXOL® from Bristol-Myers Squibb, Princeton, N.J.), docetaxel (available as TAXOTERE® from Sanofi-aventis, Bridgewater, N.J.) and the like and other compounds that act as antimicrotubule agents, such as Vincristine (ONCOVIN®, VINCASAR PFS®, VCR), Vinblastin (VELBAN®, VELSAR®) and Vinorelbine, and similar compounds. The present invention also provides methods of modulating the growth of selected cell populations, such as cancer cells, by administering a therapeutically effective amount of at least one sphingosine-1-phosphate 1 (S1P1R) receptor antagonists, and at least one antimicrotubule agent.

Abstract: The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. More specifically, the invention provides quinazolines and quinolines which inhibit, regulate, and/or modulate kinase receptor, particularly c-Met, KDF, c-Kit, flt-3 and flt-4, signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. The present invention also provides methods for making compounds as mentioned above, and compositions which contain these compounds.

Abstract: Human MELK genes are identified as modulators of the RAC pathway, and thus are therapeutic targets for disorders associated with defective RAC function. Methods for identifying modulators of RAC, comprising screening for agents that modulate the activity of MELK are provided.

Abstract: Human MAPK genes are identified as modulators of the Rac, axin, and beta-catenin pathways, and thus are therapeutic targets for disorders associated with defective Rac, axin, and beta-catenin function. Methods for identifying modulators of Rac, axin, and beta-catenin, comprising screening for agents that modulate the activity of MAPK are provided.

Abstract: This disclosure relates to sphingosine-1-phosphate (S1P) receptor antagonists, compositions comprising the S1P receptor antagonists and methods for using and processes for making the S1P receptor antagonists. In particularly, this disclosure relates to sphingosine-1-phosphate 1 (S1P1) receptor antagonists, compositions comprising the S1P1 receptor antagonist and methods for using the S1P1 receptor antagonist, such as in the treatment of cancer, and processes for making the S1P1 receptor antagonists.

Abstract: Compounds of formula (I), useful for inhibiting PIM-I and/or PIM-3: and pharmaceutically acceptable salts thereof, wherein Y, Z, R1, R3, Q, X and R4 are as defined above. Pharmaceutical compositions and methods of treating diseases and conditions, such as cancer, are also disclosed.