DISCOVERY OF NOVEL LOW-MOLECULAR-WEIGHT GPR54 AGONISTS

摘要

Metastin (kisspeptin-54) is a product of the metastasis suppressor gene KiSS-1. This C-terminally amidated peptide was identified as the endogenous ligand for the G-protein coupled receptor GPR54 (hOT7T175, AXOR12) . The residues of metastin critical for GPR54 agonistic activity are located at the C-terminal decapeptide amide, kisspeptin-10/metastin(45-54). It has been reported that metastin-GPR54 signaling regulates gonadotropin secretion and negatively regulates cancer metastasis. Therefore, GPR54 agonists could be promising therapeutic agents for hypogonadotropic hypogonadism and metastatic cancers. In order to develop potent low-molecular-weight GPR54 agonists, structure-activity relationship (SAR) study on kisspeptin-10 was conducted.