Drug Discovery for Orphan G Protein-Coupled Receptors

Focus: 

To identify compounds that interact with “orphan” G protein-coupled receptors and develop those compounds into new drug candidates

Anticipated Impact: 

New drugs for major medical conditions such as cancer, obesity, and neurological disorders. A new non-profit initiative to advance the life sciences sector and improve health and economic growth in Washington.

Abstract: 

G protein-coupled receptors (GPCRs) are a family of proteins that are involved in many biological processes, with 30 to 40% of current drugs having their effect by binding to these targets. There are approximately 120 GPCRs (termed orphan GPCRs) with no known ligands. Given the importance of GPCRs in health and disease, discovery of ligands for the orphans is expected to create potential new drug candidates. Using a proprietary screening technology, Omeros will identify compounds that interact with orphan GPCRs, modify their structures as needed to improve their function as drugs, and test their activity in laboratory studies. Omeros’ GPCR platform technology could result in new therapeutics to treat conditions as diverse as cancer, obesity, and neurological disorders.

In the event that the Omeros GPCR program achieves commercial success, a portion of the resulting proceeds payable under the grant award agreement will be used to fund a non-profit organization to enhance the competitiveness of Washington’s life sciences sector, improve health and healthcare across the state and beyond, and provide statewide economic returns.  This new life sciences initiative, with a mission complementary to LSDF’s, would have close working relationships with LSDF and other entities focused on promoting the life sciences in Washington. 

As currently anticipated, the life sciences initiative will take the form of a new non-profit entity that is expected to make grants to non-profit life science entities in Washington to both support cutting-edge research and accelerate the translation of such research to public benefit. The organization could also provide investment capital for Washington-based, early-stage companies seeking to move research results into the commercial marketplace.

 See also:
     • 2011 LSDF/WBBA Open House Poster
     • Presentation by Gregory Demopulos, Omeros Corporation, Drug Discovery for Orphan G Protein-Coupled Receptors (PDF)
 

Drug Discovery for Orphan G Protein-Coupled Receptors

Grant Update

Principal Investigator:
Gregory A. Demopulos
Grantee Organization:
Omeros Corporation
Grant Title:
Drug Discovery for Orphan G Protein-Coupled Receptors
Grant Cohort and Year:
2010 Opportunity (05)
Grant Period:
10/21/2010 - 10/20/2012 (Completed)
Grant Amount:
$5,000,000
Omeros is screening orphan GPCRs against its small-molecule chemical libraries using its proprietary, high-throughput cellular redistribution assay (CRA). The CRA detects receptor antagonists, agonists and inverse agonists. Omeros has announced that it has identified and confirmed sets of compounds that interact selectively with 46 orphan receptors linked to metastatic melanoma (GPR19), esophageal squamous cell carcinoma and obesity-related type-2 diabetes (GPR39), hepatocellular carcinoma (GPR80), several types of cancer (GPR65/TDAG8), squamous cell carcinoma (GPR87), ovarian cancer (GPR150), pancreatic cancer (GPR182), acute lymphoblastic leukemia (P2Y8/P2RY8), ovarian and prostate cancer (OGR1), arterial stiffness (GPR25), sleep disorders (OPN4), cognitive disorders (GPR12), torpor or “suspended animation” and bipolar disorder (GPR50), anxiety disorders (GPR31), schizophrenia (GPR52, GPR153), autism (GPR63), bipolar disorder and schizophrenia (GPR78), memory and inflammatory conditions (GPR83), psychotic and metabolic disorders (GPR27, GPR85, GPR173), cognition (GPR151), cognitive impairments (MAS1), inflammatory responses (GPR32), obesity and diabetes (GPR21), appetite control (GPR82, GPR101), immunological disorders (CCRL2), rheumatoid arthritis and HIV-mediated enteropathy (GPR15), respiratory and immune disorders (GPR141), humoral immunity (GPR183), multiple sclerosis (GPR17), osteoarthritis (GPR22), motor control (GPR139), congenital cataracts and birth defects of the brain and spinal cord (GPR161), regulation of hematopoietic stem cell differentiation (GPR171), cancer stem cells and the self-renewal and maintenance of adult stem cells (LGR4), long-term wound repair, including the formation of new hair follicles (LGR6) and pain (MRGE). In addition, Omeros has unlocked GPR20, GPR45, GPR135, GPR162, MRGF and OPN5, which have not yet been definitively tied to any specific indications but are expressed preferentially in the gastrointestinal tract (GPR20), brain (GPR45, GPR135 and GPR162) and eye, brain, testes, spinal cord (OPN5) and dorsal root ganglia (MRGF).

Impact in Washington

Location of LSDF Grantee
Locations of Collaborations/Areas of Impact
Seattle

Legislative Districts:
11, 34, 36, 37, 43, 46

Health Impacts

Drug Discovery for Orphan G Protein-Coupled Receptors