SEATTLE, Feb. 23, 2012 /PRNewswire/ -- Omeros Corporation (NASDAQ: OMER) today reported that it has identified compounds that interact selectively with each of OGR1, GPR21, GPR50 and GPR52, bringing the total number of orphan G protein-coupled receptors (GPCRs) unlocked by Omeros to 27, representing 35 percent of the Class A orphan GPCRs. There are approximately 120 orphan GPCRs, and Omeros expects to unlock a large percentage of them, focusing first on Class A orphan GPCRs.
OGR1, a proton-sensing receptor, is linked to ovarian and prostate cancer as well as osteoporosis and asthma. GPR21 is associated with obesity and diabetes. GPR50, a member of the melatonin receptor subfamily, is linked to the induction of torpor or "suspended animation" in mammals, greatly depressing physiologic processes such as respiration, cardiac function and metabolic rate to allow continued survival in harsh environments. Drugs targeting GPR50 could be used to alter whole-body metabolism for a wide range of medical indications. GPR52 is tied to schizophrenia. Omeros is in the process of filing broad patent applications around its unlocked orphan GPCRs and compound optimization efforts are underway.
"This latest series of unlocked orphans, connected to indications spanning cancer, torpor, diabetes and psychotic disorders, underscores the breadth of important therapeutic areas linked to orphan GPCRs," said Gregory A. Demopulos, M.D., chairman and chief executive officer of Omeros. "We are establishing intellectual property positions around these and all of our unlocked orphans. Our GPCR program remains on track, and we expect to complete the screening of all Class A orphan GPCRs in 2012."
Ongoing GPCR Program
Omeros is 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 27 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), ovarian and prostate cancer (OGR1), arterial stiffness (GPR25), sleep disorders (OPN4), cognitive disorders (GPR12), torpor or "suspended animation" (GPR50), anxiety disorders (GPR31), schizophrenia (GPR52), bipolar disorder and schizophrenia (GPR78), psychotic and metabolic disorders (GPR27, GPR85, GPR173), cognitive impairments (MAS1), inflammatory responses (GPR32), obesity and diabetes (GPR21), 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 GPR20 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.