BPRPT0245

BPRPT0245 is a small molecule inhibitor of prostaglandin reductase 2 (PTGR2) being investigated for the treatment of type 2 diabetes and obesity. PTGR2 is an enzyme that metabolizes 15-keto-prostaglandin E2 (15-keto-PGE2), an endogenous covalent ligand for peroxisome proliferator-activated receptor γ (PPARγ). By inhibiting PTGR2, BPRPT0245 increases the levels of 15-keto-PGE2, which in turn activates PPARγ to improve systemic insulin sensitivity and glucose homeostasis. Preclinical studies in obese mice have demonstrated that BPRPT0245 can protect against diet-induced obesity, insulin resistance, and hepatic steatosis. Notably, this mechanism of increasing endogenous PPARγ ligands appears to avoid the common side effects associated with synthetic PPARγ agonists (thiazolidinediones), such as fluid retention, osteoporosis, and increased adiposity.