Oct. 3, 2013
/PRNewswire/ -- Omeros Corporation (NASDAQ: OMER) today announced that it has identified compounds that functionally interact with each of six additional orphan G protein-coupled receptors (GPCRs) that have been linked to a wide range of diseases in the areas of neurologic disorders, cardiovascular disease and oncology. Identification of compounds that functionally interact with orphan GPCRs facilitates the development of drugs that target those receptors. Omeros has now unlocked 52 Class A orphan GPCRs, representing approximately 65 percent of these targets.
The six additional orphan GPCRs unlocked by Omeros are GPR37, GPR37L1, GPR132, GPR174, GPR176 and LGR5. GPR37 has been linked to Parkinson's disease. GPR37L1, GPR132 and GPR176 are associated with cardiovascular indications, specifically hypertension and cardiac hypertrophy (GPR37L1 and GPR132) and atherosclerosis (GPR176). GPR174 has been linked to melanoma and Grave's disease, while LGR5 is expressed in cancer stem cells and has been associated with esophageal adenocarcinoma.
In addition, using its proprietary Cellular Redistribution Assay (CRA) technology, which has already successfully "unlocked" 52 Class A orphan GPCRs, Omeros has identified small molecules that interact with two non-orphan Class B GPCRs; the glucagon-like peptide 1 receptor (GLP-1R) and the parathyroid hormone 1 receptor (PTH-1R). Both of these receptors are established drug targets—GLP-1R for diabetes and PTH-1R for osteoporosis. The marketed drugs currently available that target these receptors are all injectable, with 2012 annual sales of GLP-1R agents and PTH-1R agents exceeding
, respectively. Omeros' identification of small molecules targeting GLP-1R and PTH-1R could lead to the development of oral medications for these diseases that provide dosing advantages over the injectable agents on the market. Omeros is in the process of filing broad patent applications around its discoveries, and compound optimization efforts are in progress.
"Using our proprietary technology, we continue to add to the number of druggable Class A orphan GPCRs – now 52 and spanning a broad range of important disorders – that we believe Omeros exclusively controls," said
Gregory A. Demopulos
, M.D., chairman and chief executive officer of Omeros. "Our team has now also turned to Class B GPCRs, starting with two receptors that are commercially validated but whose corresponding marketed drugs are only peptides or proteins, requiring daily or weekly injections. By identifying small molecules that functionally interact with these receptors, Omeros is opening the door to new oral treatments for diabetes and bone loss."
Ongoing GPCR Program
Omeros is screening orphan GPCRs against its small-molecule chemical libraries using its proprietary, high-throughput CRA technology. 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 52 orphan receptors linked to metastatic melanoma and lung cancer (GPR19), renal cell carcinoma, ovarian cancer and inflammatory conditions (GPR65/TDAG8), ovarian cancer, prostate cancer, bone diseases and asthma (GPR68/OGR1), hepatocellular carcinoma (GPR80), squamous cell carcinomas, bladder carcinoma, hepatocellular carcinoma and lung cancer (GPR87), ovarian cancer (GPR150), metastatic epithelial cancers, congenital cataracts and birth defects of the brain and spinal cord (GPR161), melanoma and Grave's disease (GPR174), cancer stem cells and self-renewal and maintenance of adult stem cells (LGR4, LGR5), esophageal adenocarcinoma (LGR5), leukemia (P2Y8/P2RY8), arterial stiffness (GPR25), hypertension and cardiac hypertrophy (GPR37L1), atherosclerosis (GPR132 and GPR176), multiple sclerosis, spinal cord injury, traumatic brain injury (GPR17),anxiety disorders (GPR31), Parkinson's disease (GPR37), schizophrenia (GPR52, GPR153), autism (GPR63), bipolar disorder (GPR78), anxiety, post-traumatic stress disorder, body weight abnormalities and autoimmune diseases (GPR83), motor control (GPR139), schizophrenia, cognitive impairments and mood disorders (GPR151), cognitive impairments, blood pressure abnormalities and colon cancer (MAS1), pain (MRGE), circadian rhythm irregularities and sleep disorders (OPN4), obesity, cognitive impairments and motor disorders (GPR12), obesity and diabetes (GPR21), obesity-related type-2 diabetes (GPR39), obesity, metabolic disorders, thermoregulation, mood disorder and bipolar disorder (GPR50), appetite control (GPR82, GPR101), metabolic and psychotic disorders (SREB1/GPR27, SREB2/GPR85, SREB3/GPR173), rheumatoid arthritis (CCRL2), rheumatoid arthritis and HIV-mediated enteropathy (GPR15), osteoarthritis (GPR22), acute inflammatory responses (GPR32), humoral immunity (GPR183), regulation of hematopoietic stem cell differentiation (GPR171), long-term wound repair, including the formation of new hair follicles (LGR6). In addition, Omeros has unlocked GPR20, GPR45, GPR135, GPR141, GPR162, GPR182, MRGF and OPN5, which are expressed preferentially in the gastrointestinal tract (GPR20), brain (GPR45, GPR135, GPR162 and OPN5), dorsal root ganglia (MRGF), bone marrow, spleen, skin and lung (GPR141) and throughout the body (GPR182).
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, and compounds acting through serotonin and dopamine receptors.
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 82 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.