Abstract: The invention provides methods and compositions for screening for pharmacological agents which regulate gene expression in mammals. An exemplary assay involves (a) contacting a mammalian cell comprising a knock-in mutant of a targeted native allele encoding a reporter of gene expression, wherein the expression of the reporter is under the control of the gene expression regulatory sequences of the native allele, with a candidate agent under conditions whereby but for the presence of the agent, the reporter is expressed at a first expression level; and, (b) measuring the expression of the reporter to obtain a second expression level, wherein a difference between the first and second expression levels indicates that the candidate agent modulates gene expression.

Abstract: Modulators of PPAR&ggr; activity are provided which are useful in pharmaceutical compositions and methods for the treatment of conditions such as type II diabetes and obesity.

Abstract: The invention provides isolated nucleic acid and amino acid sequences of novel receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of the receptors.

Abstract: Methods for identifying modulators of nuclear hormone receptor function comprise the steps of (a) forming a mixture comprising a nuclear hormone receptor, a peptide sensor and a candidate agent, but not a natural coactivator protein of the receptor, wherein the sensor provides direct, in vitro binding to the receptor under assay conditions; (b) measuring an agent-biased binding of the sensor to the receptor; and (c) comparing the agent-biased binding with a corresponding unbiased binding of the sensor to the receptor. In particular embodiments, the sensor comprises an amphipathic alpha helix nuclear hormone interacting domain comprising a recited nuclear hormone transcriptional coactivator motif sequence, the sensor is present at sub-micromolar concentration, the binding reaction occurs in solution, the sensor comprises a fluorescent label and the measuring step comprises detecting fluorescence polarization of the label.

Abstract: Compounds, compositions and methods that are useful in the treatment of inflammatory and immune conditions and diseases are provided herein. In particular, the invention provides compounds which modulate the expression and/or function of a chemokine receptor. The subject methods are useful for the treatment of inflammatory and immunoregulatory disorders and diseases, such as multiple sclerosis, rheumatoid arthritis and type I diabetes.

Abstract: Salts of pyrimidine derivatives are provided having the formula: 1

Abstract: The present invention provides nucleic acid and protein sequences for a novel protein, PRC17, and methods, reagents, and kits for diagnosing and treating cancer in a mammal, e.g., a human. This invention is based upon the discovery that the novel PRC17 is overexpressed and/or amplified in cancer. Methods to detect cancer or a propensity to develop cancer, to monitor the efficacy of a cancer treatment, and to treat cancer, by inhibiting the expression and/or activity of PRC17 in a cancer cell are included.

Abstract: The invention provides isolated nucleic acid and amino acid sequences of novel receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of the receptors.

Abstract: Compounds and compositions are provided which are useful for the treatment of viral infections, particularly human Cytomegalovirus infection. The compounds include novel pyrimidine-based derivatives.

Abstract: The invention provides isolated nucleic acid and amino acid sequences of novel G-protein coupled receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of G-protein coupled receptors.

Abstract: Compounds, compositions and methods are provided that are useful in the treatment and/or prevention of a condition or disorder mediated by a G-protein coupled receptor. In particular, the compounds of the invention are useful in the treatment and/or prevention of eating disorders, obesity, anxiety disorders and mood disorders.

Abstract: Compounds, compositions and methods are provided that are useful in the treatment of chemokine receptor-mediated conditions and diseases. In particular, the invention provides compounds which modulate CCR4 function or a CCR4-mediated response. The subject compounds and compositions are useful for the treatment or prevention of inflammatory conditions and diseases.

Abstract: The present application provides methods of assaying for compounds that inhibit premature translation termination and nonsense mediated RNA decay in cells.

Abstract: This invention provides methods and compositions that are useful for modulating cholesterol levels in a cell, and for identifying compounds that can tested for ability to modulate cholesterol levels in mammals. In vitro assays for prescreening to identify candidate therapeutic agents for modulation of cholesterol metabolism are provided. These methods involve analyzing the effect of a test compound on the binding of FXR to a ligand for FXR. Such ligands include, for example, bile acids, coactivators, and corepressors. The methods and compositions involve modulating FXR-mediated expression of genes involved in cholesterol metabolism.

Abstract: The present invention provides nucleic acid and protein sequences for a Th-1 cell-specific protein, Chandra. The herein-disclosed sequences can be used for any of a number of purposes, including for the specific detection of Th1 lymphocytes, for the identification of molecules that associate with and/or modulate the activity of Chandra, to diagnose any of a number of conditions associated with Th1 or Th2 cell activity, or to modulate the number and/or activity of Th1 or Th2 lymphocytes in a mammal.

Abstract: Combination therapies are provided for the treatment of proliferative disorders which use a pentafluorobenzenesulfonamide of formula I and an antineoplastic agent such as gemcitabine or paclitaxel.

Abstract: Compounds and compositions are provided that bind to the CCR4 chemokine receptor and which are useful for treating diseases associated with CCR4 activity, such as contact hypersensitivity.

Abstract: The invention provides methods and compositions relating to novel pentafluorophenylsulfonamide derivatives and analogs and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, vascular restenosis, microbial infections, and psoriasis, or as lead compounds for the development of such agents.

Abstract: Compounds, compositions and methods that are useful in the treatment of inflammatory and immune conditions and diseases are provided herein. In particular, the invention provides compounds which modulate the expression and/or function of a chemokine receptor. The subject methods are useful for the treatment of inflammatory and immunoregulatory disorders and diseases, such as multiple sclerosis, rheumatoid arthritis and type I diabetes.

Abstract: The invention provides methods and compositions relating to an I&kgr;B kinase, IKK-&agr;, and related nucleic acids. The polypeptides may be produced recombinantly from transformed host cells from the disclosed IKK-&agr; encoding nucleic acids or purified from human cells. The invention provides isolated IKK-&agr; hybridization probes and primers capable of specifically hybridizing with the disclosed IKK-&agr; genes, IKK-&agr;-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.