Daniel O Connolly

US Patent:

6902902, Jun 7, 2005

Filed:

Dec 6, 2002

Appl. No.:

10/314048

Inventors:

David J. Unett - San Diego CA, US
Ruoping Chen - San Diego CA, US
Jeremy G. Richman - San Diego CA, US
Daniel T. Connolly - Carlsbad CA, US
Yaron Hakak - San Diego CA, US
Dominic P. Behan - San Diego CA, US
Derek T. Chalmers - Cardiff CA, US

Assignee:

Arena Pharmaceuticals, Inc. - San Diego CA

International Classification:

G01N033/53
C07K014/00
C07H021/04

US Classification:

435 71, 435 72, 435 721, 435 691, 4352351, 4353201, 435375, 530300, 530350, 536 231

Abstract:

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.

US Patent:

7611832, Nov 3, 2009

Filed:

Jul 25, 2003

Appl. No.:

10/523100

Inventors:

John W. Adams - San Diego CA, US
Daniel T. Connolly - Solana Beach CA, US

Assignee:

Arena Pharmaceuticals, Inc. - San Diego CA

International Classification:

C12Q 1/00
C07K 14/705

US Classification:

435 4, 530350

Abstract:

The present invention relates to methods of identifying whether a candidate compound is a modulator of an orphan G protein-coupled receptor (GPCR). Preferably the GPCR is human. In some embodiments, the GPCR is expressed endogenously by cardiomyocytes. In some embodiments, the GPCR is coupled to Gi and lowers the level of intracellular cAMP. In some embodiments, overexpression of the GPCR promotes survival of cardiomyocytes. In some embodiments, overexpression of the GPCR rescues cardiomyoctes from hypoxia/reoxygenation induced apoptosis. In some embodiments, the GPCR is down-regulated in individuals with congestive heart failure. Agonists of the invention are envisioned to be useful as therapeutic agents for the treatment of ischemic heart disease, including myocardial infarction, post-myocardial infarction remodeling, and congestive heart failure.

US Patent:

7829298, Nov 9, 2010

Filed:

Aug 31, 2004

Appl. No.:

10/930662

Inventors:

David J. Unett - San Diego CA, US
Ruoping Chen - San Diego CA, US
Jeremy G. Richman - San Diego CA, US
Daniel T. Connolly - Solana Beach CA, US
Huong T. Dang - San Diego CA, US
Bryan J. Choi - Bonita CA, US
James N. Leonard - San Diego CA, US
Yaron Hakak - San Diego CA, US
Chen W. Liaw - San Diego CA, US
Dominic P. Behan - San Diego CA, US
Derek T. Chalmers - Cardiff CA, US
Michael R. Lerner - Rancho Santa Fe CA, US
Kevin P. Lowitz - Sunnyvale CA, US

Assignee:

Arena Pharmaceuticals, Inc. - San Diego CA

International Classification:

G01N 33/53

US Classification:

435 72

Abstract:

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.

US Patent:

8017313, Sep 13, 2011

Filed:

Jun 17, 2004

Appl. No.:

10/561132

Inventors:

John W. Adams - San Diego CA, US
Daniel T. Connolly - San Diego CA, US

Assignee:

Arena Pharmaceuticals, Inc. - San Diego CA

International Classification:

C12Q 1/00
C07K 14/705

US Classification:

435 4, 530350

Abstract:

The present invention relates to methods of identifying whether a candidate compound is a modulator of a G protein-coupled receptor (GPCR). In some embodiments, the GPCR is mammalian, preferably human. In some embodiments, the GPCR is expressed endogenously by cardiomyocytes. In some embodiments, the GPCR is coupled to Gq. In some embodiments, the GPCR increases the intracellular level of inositol 1,4,5-triphosphate (IP3). In some embodiments, a modulator of the GPCR is a modulator of cardiomyocyte hypertrophy. The present invention further relates to methods of using a modulator of the GPCR. Preferred modulators are inverse agonists and antagonists. Inverse agonists and antagonists of the invention are useful as therapeutic agents for the prevention or treatment of heart disease, including hypertrophic cardiomyopathy and congestive heart failure, in particular hypertrophic cardiomyopathy resulting from post-myocardial infarction remodeling, cardiac valve disease, sustained cardiac afterload, myocarditis, and familial hypertrophic cardiomyopathy.

US Patent:

20050004178, Jan 6, 2005

Filed:

Jul 23, 2004

Appl. No.:

10/897815

Inventors:

David Unett - San Diego CA, US
Ruoping Chen - San Diego CA, US
Jeremy Richman - San Diego CA, US
Daniel Connolly - Carlsbad CA, US
Chen Liaw - San Diego CA, US
Dominic Behan - San Diego CA, US
Derek Chalmers - Cardiff CA, US
Michael Lerner - Rancho Santa Fe CA, US
Huong Dang - San Diego CA, US
Bryan Choi - Bonita CA, US
James Leonard - San Diego CA, US
Yaron Hakak - San Diego CA, US
Kevin Lowitz - Sunnyvale CA, US

Assignee:

Arena Pharmaceuticals, Inc. - San Diego CA

International Classification:

A61K031/4439
G01N033/53

US Classification:

514341000, 435007100

Abstract:

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.

US Patent:

20070079392, Apr 5, 2007

Filed:

Nov 22, 2006

Appl. No.:

11/603625

Inventors:

Chen Liaw - San Diego CA, US
Dominic Behan - San Diego CA, US
Derek Chalmers - Cardiff CA, US
Michael Lerner - Rancho Santa Fe CA, US
Huong Dang - San Diego CA, US
Bryan Choi - Bonita CA, US
James Leonard - San Diego CA, US
Yaron Hakak - San Diego CA, US
Kevin Lowitz - Sunnyvale CA, US
David Unett - San Diego CA, US
Ruoping Chen - San Diego CA, US
Jeremy Richman - San Diego CA, US
Daniel Connolly - Carlsbad CA, US

Assignee:

Arena Pharmaceuticals, Inc. - San Diego CA

International Classification:

A01K 67/027
G01N 33/53
C12P 21/06
C07D 403/02
C07K 14/705

US Classification:

800014000, 435007100, 800018000, 435069100, 435320100, 435325000, 546268100, 514341000

Abstract:

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.

US Patent:

20070224127, Sep 27, 2007

Filed:

Nov 22, 2006

Appl. No.:

11/604179

Inventors:

John Adams - San Diego CA, US
Daniel Connolly - Solana Beach CA, US

International Classification:

A61K 49/00
A01K 67/027
C12N 5/10
G01N 33/53
G01N 33/567
G01N 33/569

US Classification:

424009200, 435325000, 435007200, 435007210, 435007310, 800008000

Abstract:

The present invention relates to methods of identifying whether a candidate compound is a modulator of an orphan G protein-coupled receptor (GPCR). Preferably the GPCR is human. In some embodiments, the GPCR is expressed endogenously by cardiomyocytes. In some embodiments, the GPCR is coupled to Gi and lowers the level of intracellular cAMP. In some embodiments, overexpression of the GPCR promotes survival of cardiomyocytes. In some embodiments, overexpression of the GPCR rescues cardiomyoctes from hypoxia/reoxygenation induced apoptosis. In some embodiments, the GPCR is down-regulated in individuals with congestive heart failure. Agonists of the invention are envisioned to be useful as therapeutic agents for the treatment of ischemic heart disease, including myocardial infarction, post-myocardial infarction remodeling, and congestive heart failure.

US Patent:

20070231263, Oct 4, 2007

Filed:

Nov 22, 2006

Appl. No.:

11/604178

Inventors:

Jun Qiu - San Diego CA, US
Robert Webb - San Diego CA, US
David Unett - San Deigo CA, US
Joel Gatlin - San Diego CA, US
Daniel Connolly - Solana Beach CA, US

International Classification:

A61K 48/00
A61K 31/44
A61K 49/00
C07D 417/00
C07K 14/00
C12N 5/06

US Classification:

424009100, 435366000, 514002000, 514336000, 530350000, 546268700

Abstract:

The present invention relates to methods of identifying whether one or more candidate compounds is a modulator of a G protein-coupled receptor (GPCR) or a modulator of blood glucose concentration. In certain embodiments, the GPCR is human. The present invention also relates to methods of using a modulator of the GPCR. A preferred modulator is agonist. Agonists of the invention are useful as therapeutic agents for lowering blood glucose concentration, for preventing or treating certain metabolic disorders, such as insulin resistance, impaired glucose tolerance, and diabetes, and for preventing or treating a complication of an elevated blood glucose concentration, such as atherosclerosis, heart disease, stroke, hypertension and peripheral vascular disease.