B7-33

B7-33 is a synthetic single-chain peptide analogue of human relaxin-2 (H2 relaxin), a peptide hormone known for potent vasodilatory, anti-fibrotic, and cardioprotective properties. Native relaxin has a complex two-chain structure held together by three disulfide bridges, much like insulin, which makes it difficult and expensive to synthesize and gives it a short half-life; B7-33 was developed by Hossain, Bathgate, and colleagues at the Florey Institute in Australia as a minimized, single-chain derivative based on relaxin's B-chain that retains the hormone's beneficial activity in a far simpler molecule ^[1][3].

Mechanistically, B7-33 binds the relaxin family peptide receptor 1 (RXFP1), a G protein-coupled receptor, and acts as the first functionally selective (biased) agonist of that receptor. Where native relaxin strongly drives cyclic AMP signaling, which has been linked to tumor-promoting effects, B7-33 preferentially activates the extracellular signal-regulated kinase (ERK) pathway that mediates the anti-fibrotic response, and notably it did not promote prostate tumor growth in testing ^[1]. In preclinical rodent models of heart and lung disease, B7-33 prevented or reversed fibrosis and organ dysfunction with potency comparable to relaxin itself ^[1].

B7-33 is an investigational research peptide and has not been approved for any clinical use. A practical limitation is its very short circulating half-life, and later work has focused on stabilizing it through fatty-acid conjugation and nanoparticle delivery to enable prolonged activity and even oral administration in animal models of cardiomyopathy ^[2][4]. It is handled as a research chemical, and its human efficacy and safety remain uncharacterized.

B7-33 is a single-chain peptide agonist of the relaxin receptor (RXFP1) investigated preclinically for fibrosis and tissue remodeling; it has essentially no published human safety data and is sold as a research chemical. Because relaxin signaling affects blood vessels, the heart and collagen turnover, plausible effects include hemodynamic changes such as lowered blood pressure and increased heart rate, and its immunogenicity and long-term effects in humans are unknown.

B7-33 is a single-chain peptide derived from the B-chain of human relaxin-2, engineered by researchers at the Florey Institute in Melbourne, Australia, as a simplified and functionally selective agonist of the relaxin receptor RXFP1. It was described in a 2016 report in the journal Chemical Science, which showed that the single chain could reproduce relaxin's anti-fibrotic actions while biasing signaling toward the tissue-protective ERK pathway rather than the cAMP pathway linked to relaxin's tumor-promoting risk. Subsequent medicinal-chemistry work addressed the peptide's very short serum stability through fatty-acid and nanoparticle conjugation. It remains an investigational compound studied in preclinical models rather than an approved therapy.

B7-33 is viewed as a promising anti-fibrotic peptide, notable for capturing much of full-length relaxin's tissue-protective activity in a far simpler single-chain molecule. Interest centers on its functional selectivity, since biasing signaling toward the ERK pathway is thought to preserve the beneficial anti-fibrotic and cardioprotective effects while avoiding a signaling arm associated with tumor promotion. In multiple rodent models of heart and lung disease it prevented or reversed organ fibrosis with a potency similar to native relaxin, which has drawn attention to its therapeutic potential. Honest appraisal stresses that it remains investigational, that its native form has a serum half-life of only about six minutes, and that there are no human data. It is best regarded as an encouraging research peptide still early in its development.