Discovery Technologies

Omeros’ research technologies enable
the discovery of next-generation
therapeutics to improve – and to
save – the lives of patients.

Let science lead the way

G Protein-coupled Receptor (GPCR) Deorphanization

We developed the first – and we believe the only – high-throughput system to identify synthetic ligands, including antagonists, agonists, and inverse agonists, that bind to and affect the function of orphan G protein-coupled receptors. This proprietary system has “unlocked” 54 orphan GPCRs to date. For comparison, in the same timeframe, the rest of the world collectively found synthetic ligands for only 4 orphan GPCRs.

Significance of GPCRs

GPCRs, which are cell surface membrane proteins involved in mediating both sensory and nonsensory functions, comprise one of the largest families of proteins in the genomes of multicellular organisms. The GPCR family represents an important source of drug discovery. GPCR-targeted drugs account for nearly 40% of all drugs sold worldwide.

Although GPCRs form a super-family of receptors, individual GPCRs display a high degree of specificity and affinity for the functionally active molecules, or ligands, that bind to a given receptor. When activated by its ligand, the GPCR interacts with intracellular G proteins, resulting in a cascade of signaling events inside the cell that ultimately leads to the particular function linked to the receptor. There are 370 non-sensory GPCRs with known ligands and 167 of them are drug targets – 108 for FDA approved medications and 66 for molecules in clinical trials.

Without a known ligand, there is no template for medicinal chemistry and no way to identify the GPCR’s signaling pathway. This means that drugs are very difficult to develop against orphan GPCRs. Only 7 of the 116 orphan GPCRs have had a drug developed against them. “Unlocking” an orphan GPCR by identifying one or more of its respective ligands can lead to the development of drugs that act at the previously undruggable receptor.

G protein-coupled receptor (GPCR) – cell surface membrane protein

GPCR deorphanization technology

GPCR Deorphanization Technology

Omeros developed a proprietary cellular redistribution assay (CRA) that enables high-throughput identification of synthetic ligands, including antagonists, agonists and inverse agonists, that bind to and affect the function of orphan GPCRs. We believe that ours is the first and only assay capable of finding synthetic ligands for GPCRs in high throughput. Using our CRA, we have successfully identified and confirmed sets of compounds that interact selectively with the orphan receptors listed below.

GPCR Targets for Discovery

Omeros has identified and confirmed sets of compounds that interact selectively with the following orphan receptors:

GPR12Obesity, cognitive impairments
GPR21Obesity, diabetes
GPR22Cardiovascular diseases, anxiety
GPR25Arterial stiffness
GPR50Metabolic disorders
GPR61Eating disorders
GPR82Appetite, body weight
GPR101Appetite, eating disorders
GPR146Dyslipidemia, diabetes
GPR171Eating disorders
GPR19Melanoma, lung cancer
GPR20Gastrointestinal stromal tumors, acute myeloid leukemia
GPR65Renal cell carcinoma, ovarian cancer, inflammation
GPR68Ovarian cancer, prostate cancer, osteoporosis
GPR80Hepatocellular carcinoma
GPR87Squamous cell carcinoma
GPR150Ovarian cancer
GPR161Triple-negative breast cancer, sarcomas
LGR4Cancer stem cells, bone diseases
LGR5Cancer stem cells, esophageal adenocarcinoma
P2Y8Leukemia lymphomas
GPR17Myelin disorders, multiple sclerosis
GPR31Anxiety disorders
GPR37Parkinson’s disease
GPR78Bipolar disorder, schizophrenia
GPR139Motor disorders
GPR151Schizophrenia, cognitive impairments
MAS1Cognitive impairments
OPN4Seasonal affective disorder, depression, jet lag, sleep disorders
SREB2/GPR85Schizophrenia, obesity
SREB3/GPR173Schizophrenia, obesity
GPR15Human immunodeficiency virus enteropathy, rheumatoid arthritis
GPR32Acute inflammatory responses
GPR83Autoimmune disease, post-traumatic stress disorder
GPR183Osteoporosis, Epstein-Barr virus infection
CCRL2Rheumatoid arthritis
LGR6Hair follicle stem cell dysfunction, wound healing

Antibody Development

Our proprietary ex vivo platform for the discovery of novel, high-affinity monoclonal antibodies utilizes a chicken B-cell lymphoma cell line. Using our platform and other know-how and techniques, we have generated antibodies against several clinically significant targets, including highly potent antibodies against MASP-2, MASP-3 and MASP-1. We continue to add antibodies to our development pipeline against these and other important targets.

Engineering antibodies - MASP-2, MASP-3, and MASP-1