Table 3.

Examples of long-acting human relaxin analogues

Compound Name	Type	Relevant features
LY3540378	Peptide agonist of RXFP1 composed of a human relaxin analogue and a serum albumin-binding VHH domain	- Developed using novel half-life extension technology - Improved diastolic dysfunction in a preclinical model of cardiac hypertrophy [52] - Clinical trial ongoing to assess the efficacy and safety in adults with worsening HFpEF [53]
SA10SC‐RLX	Single chain lipidated peptide agonist of RXFP1	- Mimics relaxin activity in in vitro and in vivo models of acute RXFP1 engagement - Potentially suitable for once daily subcutaneous administration in patients [54]
CGEN25009	Peptide agonist of RXFP1	- Prevents preclinical bleomycin-induced pulmonary fibrosis - Relaxin-like effects are dependent upon RXFP1 expression IPF human lungs [59]
B7-33	Single chain peptide agonist of RXFP1	- Anti-fibrotic effects of RLX have been replicated in preclinical models of MI, chronic allergic airways disease and obstructive nephropathy - The vasodilatory effects of RLX have been reproduced by B7–33 in rats and mice [60]
ML290	Non-peptidic RXFP1 agonist	- Humanized RXFP1 mouse serves as an invaluable tool for testing of ML290 - Suppresses fibrotic phenotypes in human cardiac fibroblasts and hepatic stellate cells, and preclinical liver fibrosis - The higher potency for cGMP accumulation indicates that ML290 may be a direct vasodilator [61]

RXFP1 relaxin family peptide receptor 1, HFpEF heart failure with preserved ejection fraction, IPF idiopathic pulmonary fibrosis, RLX relaxin-2, MI myocardial infarction, cGMP cyclic GMP