Arena Pharmaceuticals, Inc.

Kevin P Lowitz

Derek T Chalmers

Chen Wang Liaw

Dominic P Behan

Ruoping Chen

James N Leonard

David J Unett

Yaron Hakak

Daniel T Connolly

Huong T Dang

Jeremy G Richman

Bryan J Choi

Michael R Lerner

I Lin-Lin

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 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 techniques for directly identifying candidate compounds as agonists, partial agonists and/or, most preferably, inverse agonists, to endogenous, constitutively activated orphan G protein-coupled receptors. Such directly identified compounds can be utilized, most preferably, in pharmaceutical compositions

Endogenous constitutively activated G protein-coupled orphan receptors

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San Diego, CA, United States of America

Kevin P Lowitz