B7-33

Overview

B7-33 is a single-chain peptide analog of human relaxin-2 that selectively activates the relaxin family peptide receptor 1 (RXFP1). Unlike native relaxin-2, which requires a complex two-chain A/B structure connected by disulfide bonds, B7-33 achieves RXFP1 activation with a much simpler single-chain design. This makes it significantly easier and more cost-effective to synthesize. Preclinical research demonstrates potent anti-fibrotic, vasodilatory, and cardioprotective properties, positioning B7-33 as a promising therapeutic candidate for fibrotic diseases, heart failure, and vascular dysfunction.

Mechanism of action

Selectively activates RXFP1, the primary receptor for relaxin-2, triggering downstream signaling cascades that inhibit fibroblast activation and collagen deposition, promote extracellular matrix remodeling via increased matrix metalloproteinase (MMP) activity, enhance nitric oxide-mediated vasodilation, and reduce inflammatory cytokine expression. B7-33 appears to preferentially engage pERK1/2 signaling pathways while showing reduced cAMP activation compared to native relaxin-2, suggesting biased agonism at RXFP1.

Key research findings

• Potent anti-fibrotic activity across multiple organ systems
• Improved vasodilation and vascular compliance
• Cardioprotective effects and potential to attenuate cardiac remodeling
• Much simpler to synthesize than native two-chain relaxin-2
• Selective RXFP1 agonism with biased signaling profile
• Preclinical efficacy in models of heart failure and fibrosis

Research applications

Cardiovascular

• Cardiac Fibrosis — Reduces myocardial fibrosis and collagen deposition, attenuating adverse cardiac remodeling in preclinical heart failure models.
• Vasodilation — Enhances nitric oxide-mediated vasodilation, reducing vascular resistance and improving blood flow in preclinical studies.
• Heart Failure — Demonstrates cardioprotective effects in animal models of heart failure, improving cardiac function and reducing fibrotic burden.

Anti-Fibrotic

• Organ Fibrosis — Inhibits fibroblast differentiation into myofibroblasts and reduces extracellular matrix deposition in multiple organ systems.
• Renal Fibrosis — Shows protective effects against kidney fibrosis progression in preclinical disease models.