77
GPR81 antagonist to treat Metabolic Diseases
Lead Discovery Center
Small molecule
Metabolic disease
Hit To Lead or Lead Optimization
G protein-coupled receptor 81 (GPR81), known as hydroxycarboxylic acid receptor 1 (HCA1), is expressed in adipocytes and mediates antilipolytic effects through inhibition of adenylyl cyclase. The primary endogenous agonist of GPR81 is lactic acid (and its conjugate base, lactate). Lactate is an important metabolic intermediate released by skeletal muscle and other organs including the adipose tissue, which converts glucose into
lactate under the influence of insulin. Lactate is produced from glucose by adipose tissue and is involved in the antilipolytic effect of insulin, providing a new link between fat and carbohydrate metabolism.