1482500-76-4

ML-290 is a first-in-class and potent relaxin/insulin-like family peptide receptor (RXFP1) agonist and activator of anti-fibrotic genes, with an EC50 of 94 nM[1]. ML290 is a biased allosteric agonist at the relaxin receptor RXFP1.

RXFP1-Agonist-8 is a potent selective agonist of the G-protein-coupled receptor RXFP1, human relaxin/insulin-like family peptide receptor 1, with an EC50 of 94 nM in HEK293 cells and no activity with RXFP2 or RXFP3, other members of the relaxin family of receptors. RXFP1-Agonist-8 is believed to interact with an allosteric site at the ECL3 loop acting non-competitively with the natural hormone relaxin to activate RXFP1, and is the first bioavailable small-molecule agonist of human RXFP1 with good metabolic stability. Relaxin has long been known as a female hormone secreted by the corpus luteum th at helps soften the cervix and relax the pelvic ligaments in childbirth. However, Relaxin also has potent cardiovascular and renal effects, inducing a 20% increase in cardiac output, 30% decrease in systemic vascular resistance, 30% increase in global arterial compliance and 45% increase in renal blood flow during pregnancy, anti-fibrotic, vasodilatory and pro-angiogenic effects th at can be reproduced in both women and men with potential for treating various disorders including hypertensive diseases and acute heart failure.

[1] Wilson KJ, et al. Optimization of the first small-molecule relaxin/insulin-like family peptide receptor (RXFP1) agonists: Activation results in an antifibrotic gene expression profile. Eur J Med Chem. 2018 Aug 5;156:79-92. DOI:10.1016/j.ejmech.2018.06.008