ML290

ML290 is a small molecule, allosteric, biased agonist of the Relaxin family peptide receptor 1 (RXFP1). Discovered through the NIH Molecular Libraries Program and developed in collaboration with the National Center for Advancing Translational Sciences (NCATS), ML290 selectively activates the Gs-cAMP signaling pathway while exhibiting minimal recruitment of β-arrestin1 and reduced cGMP signaling compared to the native ligand, Relaxin-2. This biased signaling profile is designed to harness the vasodilatory, anti-inflammatory, and anti-fibrotic properties of RXFP1 activation while potentially improving the pharmacokinetic profile and reducing desensitization. ML290 has demonstrated efficacy in preclinical models of pulmonary hypertension, right ventricular hypertrophy, and heart failure, where it inhibits TGFβ-mediated fibrosis and vascular remodeling.