PF-05190457

PF-05190457 is a high-affinity, selective, and orally bioavailable small molecule inverse agonist of the ghrelin receptor (growth hormone secretagogue receptor type 1, GHSR). It exhibits strong selectivity for the ghrelin receptor over other targets and has demonstrated the ability to increase intracellular calcium concentration and insulin secretion from human islets in vitro. In clinical studies, it dose-dependently blocks ghrelin-induced growth hormone release, delays gastric emptying, increases heart rate transiently, and induces somnolence at higher doses. The drug was developed as a first-in-class agent with potential therapeutic applications in obesity, type 2 diabetes, alcohol use disorder, and centrally acting disorders such as insomnia. Its pharmacokinetic profile supports oral daily dosing[1][2][4][5].