Arena Pharmaceuticals, Inc.

The Salk Institute for Biological Studies

The Salk Institute of Biological Studies

Ruoping Chen

Wylie W Vale, Jr

Marilyn H Perrin

Kathy A Lewis

Cynthia J Donaldson

Chen Wang Liaw

James N Leonard

Paul Sawchenko

Derek T Chalmers

Dominic P Behan

Kevin P Lowitz

Huong T Dang

David J Unett

I-Lin Lin

Daniel T Connolly

Yaron Hakak

Jeremy G Richman

I Lin-Lin

Bryan J Choi

Michael R Lerner

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

Human orphan G protein-coupled receptors

Method of identifying a compound for inhibiting or stimulating human G protein-coupled receptors

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

Human G protein-coupled receptors

In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of &#xa3; 10 nM of CRF occupy50% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. Invention CRF-Rs can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.

Cloning and recombinant production of CRF receptor(s)

Human G protein-coupled receptors and modulators thereof for the treatment of 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

In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of 10 nM of CRF occupy 50% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. Invention CRF-Rs can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.

Cloning and recombinant production of CFR receptor(s)

In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of &lE;10 nM of CRF occupy &gE;50% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. Invention CRF-Rs can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.

Cloning and recombinant production of CRF receptor(S)

Screening assays using cloned CRF receptors

Growing community of inventors

San Diego, CA, United States of America

Ruoping Chen