The receptor for H2 relaxin peptide, RXFP1, is a potential target for the treatment of fibrosis and related disorders. However, this peptide ligand has a complex insulin-like heterodimeric (A- and B-chain) structure that is difficult to modify to improve its pharmacokinetic properties (e.g. half-life). Thus it is highly desirable to develop synthetically simplified active ligands which are easier to synthesize. We have designed and synthesized a B-chain-only analogue, B7-33 which was shown to be potent in activating pERK1/2, MMPs, and cGMP in fibroblast cells and in reducing fibrosis in four animal models (Myocardial infarction-induced heart failure model, cardiomyopathy-related cardiac fibrosis model, ovalbumin-induced chronic allergic airways disease model; and unilateral ureteral obstruction). We have recently carried out structure-activity studies on B7-33 and our preliminary data suggest that we can further truncate the peptide and can significantly improve its half-life without altering its biological activity.