Omeros Corporation reported that it has identified compounds that interact with orphan G Protein-Coupled Receptors (GPCRs) GPR27 and GPR173. These receptors, together with GPR85, an orphan GPCR that Omeros previously unlocked, form the SREB (Super Conserved Receptor Expressed in Brain) family, a unique and evolutionarily conserved family of orphan GPCRs thought to be critical in regulating neural integrity. The SREB family is linked to metabolic and psychotic disorders such as obesity and schizophrenia.

Omeros also announced that it has identified compounds that interact with GPR139, an orphan GPCR primarily located in the central nervous system that may play a role in motor control. In total, Omeros has already unlocked eight, or approximately 10 per cent, of the 81 Class A orphan GPCRs. GPCRs represent the premier family of drug targets, with more than 30 per cent of currently marketed drugs targeting only 46 GPCRs. There are approximately 120 orphan GPCRs, and Omeros, which expects to unlock a large percentage of these for drug development, is initially targeting Class A orphan GPCRs.

“We have now identified compounds for 10 per cent of the Class A orphan GPCRs,” said Gregory A Demopulos, MD, chairman and chief executive officer of Omeros. “This includes all of the known SREBs, one of the most highly conserved families of GPCRs - an achievement that could facilitate the development of new drugs targeting these receptors for the treatment of important metabolic and psychotic disorders.”

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 eight orphan receptors linked to squamous cell carcinoma (GPR87), pancreatic cancer (GPR182),metabolic and psychotic disorders(GPR27, GPR85, GPR173), appetite control (GPR101), cognitive disorders (GPR12) and motor control (GPR139). 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.

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.

Omeros is a clinical-stage biopharmaceutical company committed to discovering, developing and commercializing products focused on inflammation, coagulopathies and disorders of the central nervous system.