Abstract: Compounds of Formula 1, as shown below and defined herein: and pharmaceutically acceptable salts, synthesis, intermediates, formulations, and methods of disease treatment therewith, including cancers mediated at least in part by FAK.

Abstract: The present invention provides tumor cell preparations for use as models of the EMT process for use in the identification of anti-cancer agents, wherein said tumor cell preparations comprise cells of the epithelial tumor cell line H358, which are stimulated by receptor ligands to induce EMT, or which have been engineered to inducibly express a protein that stimulates EMT. The present invention also provides methods of identifying potential anti-cancer agents by using such tumor cell preparations to identify agents that inhibit EMT, stimulate MET, or inhibit the growth of mesenchymal-like cells. Such agents should be particularly useful when used in conjunction with other anti-cancer drugs such as EGFR and IGF-1R kinase inhibitors, which appear to be less effective at inhibiting tumor cells that have undergone an EMT.

Abstract: Compounds represented by Formula (I) or a pharmaceutically acceptable salt thereof, are inhibitors of mTOR and useful in the treatment of cancer.

Abstract: The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an IGF-1R kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an IGF-1R kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and/or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by IGF-1R kinase inhibitors. Improved methods for treating cancer patients with IGF-1R kinase inhibitors that incorporate the above methodology are also provided. Additionally, methods are provided for the identification of new biomarkers that are predictive of responsiveness of tumors to IGF-1R kinase inhibitors.

Abstract: Compounds represented by Formula (I) or a pharmaceutically acceptable salt thereof, are inhibitors of mTOR and useful in the treatment of cancer.

Abstract: This invention relates to the identification of LPA as a ligand for the G-protein coupled receptors OSGPR114 and OSGPR78. The invention is directed to new methods for screening candidate drugs for their ability to modulate the activity of OSGPR114 or OSGPR78, and new pharmaceutical agents identified by these methods. It is also directed to the use of such agents in the manufacture of medicaments for the treatment of OSGPR114 or OSGPR78 mediated diseases, and methods of treating diseases such as cancers by administering to an individual a therapeutic amount of a modulator of OSGPR114 or OSGPR78 identified by these methods.

Abstract: Salt forms of mTOR inhibitors of the Formula (I): and methods of preparation, formulation, and use in treating disease.

Abstract: A method of treating adrenocortical carcinoma with OSI-906.

Abstract: Compounds represented by Formula (I): or a pharmaceutically acceptable salt or N-oxide thereof, wherein A, Q, Y, R5, m and J are defined herein, are useful in the treatment of tumors and cancers such as mastocytosis/mast cell leukemia, gastrointestinal stromal tumors (GIST), germ cell tumors, small cell lung carcinoma (SCLC), sinonasal natural killer/T-cell lymphoma, testicular cancer (seminoma), thyroid carcinoma, malignant melanoma, ovarian carcinoma, adenoid cystic carcinoma, acute myelogenous leukemia (AML), breast carcinoma, pediatric T-cell acute lymphoblastic leukemia, neuroblastoma, mast cell leukemia, angiosarcoma, anaplastic large cell lymphoma, endometrial carcinoma, and prostate carcinoma.

Abstract: Compounds of the formula and pharmaceutically acceptable salts thereof, wherein X1, X2, X3, X4, X5, X6, X7, R1, and Q1 are defined herein, inhibit the IGF-1R enzyme and are useful for the treatment and/or prevention of hyperproliferative diseases such as cancer, inflammation, psoriasis, allergy/asthma, disease and conditions of the immune system, disease and conditions of the central nervous system.

Abstract: The present application relates to the secondary binding site of dipeptidyl peptidase IV, its relationship amongst substrates and to the modulation of substrate specificity of dipeptidyl peptidase IV (DP IV, synonym: DPP IV, CD26, EC 3.4.14.5). The application relates further to compounds that bind to the secondary binding site of DP IV and their use to modulate the substrate specificity of DP IV; methods of treatment of various DP IV mediated disorders; and screening methods for the identification of secondary binding sites on DP IV and DP IV-like enzymes.

Abstract: The present invention relates to compounds of the formula 1 and to pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein X1, R1, R2 and R3 are as defined herein. The invention also relates to pharmaceutical compositions containing the above compounds and to methods treating hyperproliferative disorders in mammals by administering the above compounds.

Abstract: Compounds represented by Formula (I): or a pharmaceutically acceptable salt or N-Oxide thereof, are useful in the treatment of cancer.

Abstract: Compounds of the formula and pharmaceuticaly acceptable salts thereof, wherein Q1 and R1 are defined herein, inhibit the IGF-1R enzyme and are useful for the treatment and/or prevention of various diseases and conditions that respond to treatment by inhibition of tyrosine kinases.

Abstract: Compounds represented by Formula (I) or a pharmaceutically acceptable salt thereof, are inhibitors of mTOR and useful in the treatment of cancer.

Abstract: Amidoaryl/amidoheteroaryl substituted thiophenes, further substituted with a heteroarylmethylamino group, are useful in the treatment of cancer.

Abstract: Compounds of the formula and pharmaceutically acceptable salts thereof, wherein n1, n2, n3, n4, G1, Q1, Z, R1, R2, R3, R4a, R4b, R5a, and R5b are defined herein, inhibit the cytochrome P450RAI enzyme and are useful for the treatment and/or prevention of various diseases and conditions which respond to treatment by retinoids and by naturally occurring retinoic acid.

Abstract: Compounds represented by Formula (I) or a pharmaceutically acceptable salt thereof, are inhibitors of mTOR and useful in the treatment of cancer.

Abstract: The present invention provides a method for treating NSCL, pancreatic, colon or breast cancer tumors or tumor metastases in a patient, comprising administering to the patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein the agent is an mTOR inhibitor, with or without additional agents or treatments, such as other anti-cancer drugs or radiation therapy. The present invention also provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein said agent is an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases.

Abstract: Compounds of the Formula and pharmaceutically acceptable salts thereof, wherein X1, X2, X3, X4, X5, X6, X7, R1, and Q1 are defined herein, inhibit protein kinase enzymes and are useful for the treatment and/or prevention of hyperproliferative diseases such as cancer, inflammation, psoriasis, allergy/asthma, disease and conditions of the immune system, disease and conditions of the central nervous system.