B7-33

B7-33 is a synthetic single-chain analogue of human relaxin-2, engineered to selectively activate the RXFP1 receptor while avoiding some of the complex off-target pharmacology of native relaxin. Relaxin is a peptide hormone naturally produced during pregnancy that remodels the cervix and relaxes pelvic ligaments, while also having systemic effects on the cardiovascular and renal systems. These systemic effects - particularly antifibrotic and vasodilatory properties - have attracted significant pharmaceutical interest.

Native relaxin is a two-chain peptide (A and B chains linked by disulfide bonds, similar in structure to insulin), which creates manufacturing complexity and stability challenges. B7-33 was developed as a single-chain simplification, retaining the key B-chain sequence (residues 7-33) that contains the receptor-binding epitope for RXFP1. By presenting this binding epitope in a single chain without the A-chain, B7-33 achieves selective RXFP1 agonism with a simpler, more stable molecule.

The antifibrotic properties of relaxin/RXFP1 signalling are mediated through multiple mechanisms: inhibition of TGF-beta-stimulated fibroblast differentiation (preventing the transformation of normal fibroblasts into myofibroblasts that deposit excess collagen), activation of matrix metalloproteinases (enzymes that degrade existing collagen), and reduced expression of profibrotic cytokines. Together, these actions both prevent new fibrosis and promote resolution of existing fibrous tissue.

In the cardiovascular context, cardiac fibrosis is a major component of heart failure progression - as the heart remodels in response to pressure overload or injury, cardiomyocytes are replaced by scar tissue that reduces contractile function. B7-33 and related relaxin analogues have shown promising results in reducing this fibrosis and improving cardiac function in heart failure models, driving interest from the cardiology research community.

B7-33 represents a newer generation of peptide research tools compared to native relaxin - more manufacturable, more stable, and potentially more receptor-selective. It is one of several anti-fibrotic peptide candidates being investigated as potential therapeutics for cardiac, renal, pulmonary, and hepatic fibrosis.