ML221

ML221 is a potent, selective small molecule antagonist of the apelin receptor (APJ, also known as APLNR). It inhibits apelin-13-mediated activation of the APJ receptor with an IC50 of approximately 0.70 μM in cAMP assays and 1.75 μM in β-arrestin assays[3][4][5][7]. ML221 displays over 37-fold selectivity for the apelin receptor compared to the closely related angiotensin II type 1 (AT1) receptor and shows no toxicity toward human hepatocytes at concentrations above 50 μM[2][7]. The compound has been used primarily as a research tool to study APJ signaling pathways, including roles in neuropathic pain and testicular function. In animal models, intrathecal administration of ML221 alleviated mechanical allodynia and heat hyperalgesia associated with chronic constriction injury-induced neuropathic pain[6], while systemic administration increased sperm concentration and testosterone levels by modulating gonadotropin release and testicular steroidogenesis[8].

Other names

4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate