Small molecule ghrelin O-acyltransferase inhibitors found using an assay to detect ghrelin O-acyltransferase activity using an acrylodan-labeled peptide mimic of ghrelin that provides for high-throughput screening for ghrelin O-acyltransferase inhibitors and detection via high performance liquid chromatography. The newly discovered class of synthetic triterpenoids efficiently inhibits ghrelin acylation by GOAT and function as covalent reversible inhibitors of GOAT. In cell studies, the most potent members of this family of compounds efficiently block ghrelin acylation at submicromolar concentrations and offer a foundation for continued development and evaluation of novel hGOAT inhibitors as therapeutics targeting disorders such obesity, type II diabetes, gastroparesis, and Prader-Willi syndrome.
