TRND8394

TRND8394 is a small molecule, biased agonist of the Relaxin Family Peptide Receptor 1 (RXFP1). Developed as a derivative of the ML290 scaffold, it selectively activates cAMP signaling while exhibiting significantly reduced recruitment of cGMP and β-arrestin1 compared to the native ligand, Relaxin-2 (RLN2). This biased signaling profile is intended to leverage the vasodilatory, anti-inflammatory, and anti-fibrotic effects of RXFP1 activation while potentially avoiding off-target or desensitization effects associated with full agonism. TRND8394 has demonstrated efficacy in experimental models of pulmonary hypertension (PH) and right ventricular (RV) hypertrophy, showing improvements in right ventricular systolic pressure and potent reductions in RV hypertrophy when administered orally. It is being investigated as a potential therapeutic for cardiopulmonary diseases, including pulmonary arterial hypertension and heart failure.