Relaxin receptor (RXFP1) / relaxin

Class

Relaxin analog/fusion or relaxin-mimetic

Notes

original target text: Relaxin receptor (RXFP1) / relaxin pathway

The relaxin receptor, RXFP1, is a G protein-coupled receptor normally activated by relaxin-2, a peptide hormone best known for its role in pregnancy, where it promotes vasodilation and connective tissue remodeling to accommodate physiological changes. Binding of relaxin to RXFP1 triggers intracellular signaling that raises cyclic AMP and activates other downstream messengers, producing vasodilatory, anti-fibrotic, and mildly pro-angiogenic effects in blood vessels, kidney, heart, and lung tissue. Because these effects counteract processes central to fibrosis and impaired blood vessel function, RXFP1 has attracted interest as a target for diseases marked by tissue scarring and vascular stiffness, most notably heart failure and fibrotic organ disease. A challenge with using the natural hormone therapeutically is its very short duration of action in the bloodstream, which has motivated the development of alternative approaches: engineered fusion proteins that extend the peptide's presence in circulation, and small molecules or biologics designed to activate RXFP1 more directly and with greater selectivity than the natural hormone alone. All of these approaches share the same underlying rationale, namely sustained or more convenient activation of a receptor whose natural signaling favors vasodilation and reduced fibrosis, translated into a longer-lasting or more practical therapeutic effect than native relaxin can provide.