Overview
Following subcutaneous administration, B7-33 undergoes rapid systemic absorption with a short plasma half-life (~30–60 min estimated). RXFP1 is expressed in cardiac fibroblasts, vascular smooth muscle, renal mesangial cells, and pulmonary arterial endothelium. In fibrotic hearts, B7-33 reduces collagen I/III deposition, downregulates CTGF and α-SMA expression in fibroblasts, and restores cardiomyocyte compliance. In pulmonary vascular models, it reduces medial wall thickening and right ventricular systolic pressure.
Proposed mechanism
B7-33 binds to the relaxin family peptide receptor 1 (RXFP1) and selectively activates the pERK1/2 signaling pathway (biased agonism) while avoiding cAMP elevation, thereby isolating the anti-fibrotic and vasodilatory benefits of relaxin. This biased signaling reduces collagen deposition, inhibits TGF-β-driven fibroblast activation, and promotes matrix metalloproteinase activity to remodel pathological extracellular matrix. The selective pathway engagement may reduce potential side effects associated with full RXFP1 agonism.
What the evidence supports
Most data comes from preclinical animal studies. Human clinical trial evidence is limited or absent.
Graded Animal
Evidence drawn from in vivo animal models or in vitro systems. Mechanistically informative; translation to humans is unproven.
Key citations
Representative primary sources, including results that did not favour the compound.
- [1]
Design and characterization of a single-chain peptide analogue of human relaxin-2
· Journal of Pharmacology and Experimental Therapeutics — Hossain et al. · 2016
- [2]
The single-chain relaxin mimetic B7-33 achieves antifibrotic efficacy equivalent to relaxin-2 in a cardiac fibrosis model
· Basic Research in Cardiology — Nair et al. · 2019
- [3]
B7-33 reduces pulmonary arterial hypertension vascular remodeling in rodent models
· Cardiovascular Research — Samuel et al. (related group) · 2020
Citation records in this build are illustrative placeholders for the design.
Reference information for research purposes. Not medical advice, and not a recommendation to use any compound. Many entries describe substances that are not approved for human use.