Arena Pharmaceuticals, Inc.

Merck + Co., Inc.

Neurocrine Biosciences, Inc.

Sibia Neurosciences, Inc.

The Salk Institute Biotechnology Industrial Associates, Inc.

Tripos, Inc.

Chen Wang Liaw

Derek T Chalmers

Dominic P Behan

Steven B Ellis

Lorrie P Daggett

William J Thomsen

Joseph F Russo

I-Lin Lin

Ruoping Chen

Tilman Oltersdorf

Aaron Pontsler

Errol B DeSouza

Timothy W Lovenberg

Chin-Chun Lu

Dimitri Emil Grigoriadis

Edwin Carl Johnson

Stephen D Hess

Qian Liu

Kevin P Lowitz

Robert C Glen

Richard J Foster

Michael S Lawless

Julian R Smith

Karin Lehmann-Bruinsma

Huong T Dang

James N Leonard

David J Unett

Yaron Hakak

Didier Jc Bagnol

Nigel R Beeley

Daniel T Connolly

Sonia Villegas

Jeremy G Richman

Joel Gatlin

Daniel Ortuño

I Lin-Lin

Dominique Maciejewski-Lenior

Michael R Lerner

William R Clevenger

Bryan J Choi

The present invention relates to methods of using a G protein-coupled receptor (GPCR) to screen one or more candidate compounds as a modulator of body mass or of adiposity or of percentage body fat in a subject or as a pharmaceutical agent for obesity and conditions related thereto. Inverse agonists and antagonists of the invention are useful as therapeutic agents for the prevention or treatment of obesity and conditions related thereto, including hypertension, insulin resistance, metabolic syndrome, Type 2 diabetes, dyslipidemia, atherosclerosis, coronary heart disease, and stroke. Agonists and partial agonists of the invention are useful as therapeutic agents for the prevention or treatment of disorders ameliorated by increasing body mass including, but not limited to, cachexia.

Methods of identifying candidate compounds of the human G protein-coupled receptor, GPR50, as modulators of body mass or adiposity

The present invention relates to methods of using a G protein-coupled receptor (GPCR) to identify whether a candidate compound is a modulator of atherogenesis. In certain embodiments, the GPCR couples to Gi. In certain embodiments, the GPCR is human. Agonists of the invention are useful as therapeutic agents for the prevention or treatment of atherosclerosis and atherosclerotic disease, including coronary artery disease, myocardial infarction, peripheral arterial disease, and ischemic stroke. Agonists of the invention are additionally useful as therapeutic agents for the prevention or treatment of conditions related to MCP-1 expression, including but not limited to rheumatoid arthritis, Crohn's disease, and multiple sclerosis.

Methods of screening for a compound that reduces atherogenesis

The invention disclosed in this patent document relates to transmembrane receptors, more particularly to a human G protein-coupled receptor for which the endogenous ligand is unknown ('orphan GPCR receptors'), and most particularly to mutated (non-endogenous) versions of the human GPCRs for evidence of constitutive activity.

Constitutively activated human G protein coupled receptors

The invention disclosed in this patent document relates to transmembrane receptors, more particularly to endogenous, human orphan G protein-coupled receptors.

Nucleic acids encoding RUP3 and methods of using same

Nucleic acids encoding the GPCR, RUP3, and methods of use thereof

The present invention relates to methods of identifying whether a candidate compound is a modulator of a G protein-coupled receptor (GPCR). In preferred embodiments, the GPCR is human. In other preferred embodiments, the GPCR is coupled to Gi and lowers the level of intracellular cAMP. In other preferred embodiments, the GPCR is expressed endogenously by adipocytes. In further preferred embodiments, the GPCR inhibits intracellular lipolysis. In other further preferred embodiments, the GPCR is a nicotinic acid receptor. The present invention also relates to methods of using a modulator of said GPCR. Preferred modulator is agonist. Agonists of the invention are useful as therapeutic agents for the prevention or treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, stroke, insulin resistance, and type 2 diabetes.

Human G protein-coupled receptors for metabolic-related disorders

Disclosed herein are non-endogenous, constitutively activated forms of the human 5-HTand human 5-HTreceptors and uses of such receptors to screen candidate compounds. Further disclosed herein are candidate compounds identified by the screening method which act at the 5HTreceptors. Yet further disclosed is a new class of compounds which act at the 5HTreceptors.

Non-endogenous, constitutively activated human serotonin receptors and small molecule modulators thereof

The invention disclosed in this patent document relates to transmembrane receptors, particularly to a human G protein-coupled receptor, more particularly to a CXC chemokine receptor subtype 3 (CXCR3), and most particularly to mutated (non-endogenous) version of the human CXCR3 for evidence of constitutive activity and uses thereof. In some embodiments the altered versions of CXCR3 are used, inter alia, for the direct identification of candidate compounds such as receptor agonists, inverse agonists, partial agonist or antagonist for use in, for example and not limitation, graft rejection; inflammatory skin disease; inflammatory bowel disease; allergic inflammation, allergic pulmonary inflammation, inflammatory demyelinating neuropathy, CNS inflammation; rheumatoid arthritis, bronchiolitis obliterans syndrome, periodontal disease and neurodegenerative disease.

Constitutively active CXCR3 G protein-coupled chemokine receptor and modulators thereof for the treatment of inflammatory disorders

Disclosed herein are constitutively activated, non-endogenous versions of endogenous human G protein-coupled receptors comprising (a) the following amino acid sequence region (C-terminus to N-terminus orientation) and/or (b) the following nucleic acid sequence region (3' to 5&#x2032; orientation) transversing the transmembrane-6 (TM6) and intracellular loop-3 (IC3) regions of the GPCR:

Non-endogenous, constitutively activated human G protein-coupled receptors

The invention disclosed in this patent document relates to transmembrane receptors, more particularly to a human G protein-coupled receptor for which the endogenous ligand is known ('known GPCRs'), and most particularly to mutated (non-endogenous) versions of the known GPCRs for use, most preferably in screening assays for the direct identification of candidate compounds as inverse agonists, agonists and partial agonists.

Non-endogenous, constitutively activated known G protein-coupled receptors

The invention disclosed in this patent document relates to transmembrane receptors, more particularly to a human G protein-coupled receptor and to mutated (non-endogenous) versions of the human GPCRs for evidence of constitutive activity.

Endogenous and non-endogenous versions of human G protein-coupled receptors

The present invention provides isolated nucleic acid molecules encoding CRFreceptors, recombinant expression vectors and host cells suitable for expressing such receptors, as well as compositions and methods which utilize such receptors.

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Growing community of inventors

San Diego, CA, United States of America

Chen Wang Liaw