Omeros Unlocks Orphan GPCRs Linked to Pancreatic Cancer and Cognitive Disorders
Press Release Source: Omeros Corporation On Wednesday March 2, 2011, 7:00 am EST
SEATTLE, March 2, 2011 /PRNewswire/ -- Omeros Corporation (Nasdaq:OMER - News) today announced that it has identified compounds that interact selectively with two orphan G protein-coupled receptors (GPCRs) linked to pancreatic cancer (GPR182) and cognitive disorders (GPR12). Together with the three previously unlocked orphans linked to squamous cell carcinoma (GPR87), obesity (GPR85) and appetite control (GPR101), Omeros has now successfully unlocked five orphan GPCRs.
GPCRs represent the premier family of drug targets, with more than 30 percent of currently marketed drugs targeting only 46 GPCRs. There are approximately 120 orphan GPCRs, and Omeros expects to unlock a large percentage of these for drug development. Omeros also announced today that it has cloned approximately 90 percent of the 81 Class A orphan GPCRs into the vector of its proprietary cellular redistribution assay (CRA). The Company is advancing these receptors toward screening in its CRA.
"The progress in our GPCR program has been rapid and we remain on track to screen all of the Class A orphan GPCRs by mid-2012," stated Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros. "Out of the seven receptors screened against only a portion of our compound libraries, we have so far identified multiple small molecules for each of five orphans, demonstrating the power of our proprietary assay to open orphan GPCRs to drug development. We have nearly completed the preparatory steps for large-scale throughput, including generation of clones and constructs as well as integrating our automation capabilities, and we expect that we will soon reach our full screening rate."
Ongoing GPCR Program
Omeros has begun screening orphan GPCRs against its small-molecule chemical libraries using its proprietary, high-throughput CRA. Omeros has announced that it has identified and confirmed sets of compounds that interact selectively with five orphan receptors linked to squamous cell carcinoma (GPR87), pancreatic cancer (GPR182), obesity (GPR85), appetite control (GPR101) and cognitive disorders (GPR12). The CRA detects receptor antagonists and agonists. Antagonists comprise the majority of marketed drugs, and all of the compounds identified so far by Omeros are antagonists.
About G Protein-Coupled Receptors
GPCRs, which mediate key physiological processes in the body, are one of the most valuable families of drug targets. According to Insight Pharma Reports, GPCR-targeting drugs represent 30 to 40 percent of marketed pharmaceuticals. Examples include Claritin® (allergy), Zantac® (ulcers and reflux), OxyContin® (pain), Lopressor® (high blood pressure), Imitrex® (migraine headache), Reglan® (nausea) and Abilify® (schizophrenia, bipolar disease and depression) as well as all other antihistamines, opioids, alpha and beta blockers, serotonergics and dopaminergics.
The industry focuses its GPCR drug discovery efforts mostly on non-sensory GPCRs. Of the 363 total non-sensory GPCRs, approximately 240 have known ligands (molecules that bind the receptors) with nearly half of those targeted either by marketed drugs (46 GPCRs) or by drugs in development (about 70 GPCRs). There are approximately 120 GPCRs with no known ligands, which are termed "orphan GPCRs." Without a known ligand, drug development for a given receptor is extremely difficult.
Omeros uses its proprietary high-throughput CRA to identify small-molecule agonists and antagonists for orphan GPCRs, unlocking them to drug development. Omeros believes that it is the first to possess the capability to unlock orphan GPCRs in high-throughput, and that currently there is no other comparable technology. Unlocking these receptors could lead to the development of drugs that act at these new targets. There is a broad range of indications linked to orphan GPCRs including cardiovascular disease, asthma, diabetes, pain, obesity, Alzheimer's disease, Parkinson's disease, multiple sclerosis, schizophrenia, learning and cognitive disorders, autism, osteoporosis, osteoarthritis and several forms of cancer.