Omeros Announces it has Unlocked 30 Percent of Class A Orphan GPCRs Five Additional Orphans Unlocked by Omeros Linked to Liver Cancer, Cognitive Impairments, Cardiovascular and Inflammatory Disorders--
SEATTLE, Jan. 10, 2012 /PRNewswire via COMTEX/ -- Omeros Corporation /quotes/zigman/109048/quotes/nls/omer OMER -1.43% today reported that it has identified compounds that interact selectively with each of GPR25, GPR32, GPR80, GPR135 and MAS1, bringing the total number of orphan G protein-coupled receptors (GPCRs) unlocked by Omeros to 23, representing 30 percent of the Class A orphan GPCRs. To date, the number of orphans unlocked by Omeros for drug development equals half of the total number of GPCRs currently targeted by more than 30 percent of all marketed drugs. There are approximately 120 orphan GPCRs and Omeros expects to unlock a large percentage of them, focusing first on Class A orphan GPCRs.
GPR25 is linked to arterial stiffness, which is associated with atherosclerosis, myocardial infarction and stroke. GPR32 is tied to acute inflammation. GPR80 is linked to hepatocellular carcinoma and MAS1 to cognitive impairment, a central component of debilitating disorders such as Alzheimer's and other dementias. No potential indications have yet been linked to GPR135, although it is expressed throughout the body and widely, and preferentially, in the brain. Omeros is in the process of filing broad patent applications around its unlocked orphan GPCRs and compound optimization efforts are underway.
"Using our proprietary high-throughput assay, we are moving rapidly through the 77 Class A orphans and expect to complete screening of them all in 2012," said Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros. "We believe the compounds that we have uniquely identified for our unlocked orphan GPCRs enable the development of drug candidates selectively targeting each of those receptors, and we are working diligently to advance, protect and capitalize on our discoveries."
Ongoing GPCR Program
Omeros has begun screening orphan GPCRs against its small-molecule chemical libraries using its proprietary, high-throughput cellular redistribution assay (CRA). Omeros has announced that it has identified and confirmed sets of compounds that interact selectively with 23 orphan receptors linked to metastatic melanoma (GPR19), esophageal squamous cell carcinoma and obesity-related type-2 diabetes (GPR39), hepatocellular carcinoma (GPR80), squamous cell carcinoma (GPR87), pancreatic cancer (GPR182), acute lymphoblastic leukemia (P2Y8/P2RY8), arterial stiffness (GPR25), sleep disorders (OPN4), cognitive disorders (GPR12), anxiety disorders (GPR31), bipolar disorder and schizophrenia (GPR78), psychotic and metabolic disorders (GPR27, GPR85, GPR173), cognitive impairments (MAS1), inflammatory responses (GPR32), appetite control (GPR101), rheumatoid arthritis and HIV-mediated enteropathy (GPR15), respiratory and immune disorders (GPR141), motor control (GPR139) and congenital cataracts and birth defects of the brain and spinal cord (GPR161). In addition, Omeros has unlocked GPR 20 and GPR135, which have not yet been tied to any indications but are expressed preferentially in the gastrointestinal tract and brain, respectively. The CRA detects receptor antagonists and agonists. Antagonists comprise the majority of marketed drugs, and all of the compounds characterized so far by Omeros are antagonists.
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.