B7-33

B7-33 is a synthetic 33-amino-acid linear peptide derived from the B-chain of human relaxin-2 (H2 relaxin). It was designed and developed by Mohammed Akhter Hossain, Ross Bathgate, and colleagues at the Florey Institute of Neuroscience and Mental Health, University of Melbourne. The compound functions as a functionally selective agonist of relaxin family peptide receptor 1 (RXFP1), the cognate receptor for native relaxin. CAS number: 1818415-56-3.

The development rationale targets a specific limitation of native relaxin. Human relaxin-2 is a two-chain peptide hormone (A-chain and B-chain) connected by three disulfide bridges, similar in overall architecture to insulin. The complex structure makes large-scale production expensive, limiting the practical accessibility of relaxin-based therapeutics. Native relaxin (as serelaxin, recombinant human relaxin-2) was tested in Phase 3 trials for acute heart failure with mixed results: the RELAX-AHF trial showed cardiovascular outcome benefit, but RELAX-AHF-2 did not confirm the survival benefit, ending the serelaxin development program for that indication.

B7-33 represents an alternative approach: a single-chain peptide containing the key RXFP1-binding residues from the relaxin B-chain (RB13, RB17, IB20), simpler to synthesize, and exhibiting biased agonism at RXFP1. Specifically, B7-33 activates ERK1/2 phosphorylation through RXFP1 without inducing the cAMP signaling that native relaxin also produces. This functional selectivity preserves the anti-fibrotic effects (which are predominantly ERK-mediated) while altering the broader signaling profile.

The Animal Evidence

Hossain et al., 2016 in Chemical Science. Original characterization of B7-33 demonstrating functionally selective RXFP1 activation (ERK without cAMP), high potency in MMP-2 induction in human cardiac fibroblasts, and lack of activity at RXFP2 (the related receptor for INSL3 peptide).

Myocardial infarction model (Devarakonda et al., 2020). B7-33 administration in mouse MI models reduced adverse cardiac remodeling, preserved cardiac function, and produced anti-fibrotic effects comparable to native relaxin.

Cardiomyopathy model (Alam et al., 2023). Isoprenaline-induced cardiomyopathy in mice was treated with B7-33, native relaxin, or the ACE inhibitor perindopril. B7-33 maintained the cardioprotective effects of relaxin and reduced left ventricular fibrosis more rapidly than perindopril.

Renal fibrosis models. B7-33 induces MMP-2 in renal myofibroblasts and reverses fibrosis in animal renal injury models.

Pulmonary fibrosis models. Anti-fibrotic effects have been documented in animal models of pulmonary fibrosis, supporting the broader anti-fibrotic positioning.

Vascular effects (Marshall et al., 2017). B7-33 produces endothelium-dependent vasodilation through endothelium-derived hyperpolarizing factor activation, paralleling native relaxin's vascular effects.

The animal dataset is substantial within the cardiovascular and renal fibrosis fields. The serelaxin development experience and the broader relaxin literature provide additional supporting context.

The Human Evidence

There is none.

No registered ClinicalTrials.gov trial exists for B7-33 specifically. No Phase 1 safety data has been published. The compound has not progressed to human dose-finding or proof-of-concept testing as of May 2026.

The serelaxin trial program provides some indirect insight into native relaxin's clinical effects, but B7-33's biased agonism profile means the effects may differ. Whether B7-33 would reproduce or improve on serelaxin's clinical outcomes is unknown and untested.

Regulatory and Legal Status

FDA. No approval. No IND filing visible in public records.

EMA. No approval.

Compounding. Not on FDA bulk drug substances list.

WADA. Not on 2026 Prohibited List.

Research-chemical availability. Some vendors offer B7-33-labeled product. Identity verification is the buyer's responsibility.

B7-33 is a functionally selective agonist of RXFP1, the cognate receptor for relaxin-2.

RXFP1 biology. Relaxin family peptide receptor 1 is a G-protein-coupled receptor with an unusual large extracellular domain containing leucine-rich repeats (LRRs) plus a low-density lipoprotein receptor class A module. Native relaxin engages both the LRR domain and the seven-transmembrane domain of RXFP1, activating Gs-cAMP signaling, Gi/o signaling, and ERK1/2 pathways.

B7-33 biased agonism. The single-chain peptide retains the key RXFP1-LRR binding residues (RB13, RB17, IB20) but lacks the additional structural elements required for full receptor engagement. The result is biased agonism: B7-33 activates ERK1/2 phosphorylation strongly but fails to engage cAMP signaling. This selective pathway activation preserves the anti-fibrotic effects (predominantly ERK-mediated) while altering the broader signaling profile.

Anti-fibrotic mechanism. RXFP1 activation in cardiac fibroblasts and renal myofibroblasts increases expression of MMP-2 (matrix metalloproteinase-2), a collagen-degrading enzyme. Increased MMP-2 activity counteracts the excessive collagen deposition that characterizes fibrosis. B7-33 also reduces TGF-beta1 production, a master regulator of fibrotic gene programs. The combined effect is reduction in fibrotic tissue accumulation and reversal of established fibrosis in animal models.

Cardiovascular effects. Beyond anti-fibrotic action, B7-33 produces endothelium-dependent vasodilation through endothelium-derived hyperpolarizing factor (EDH) pathways, paralleling native relaxin's vascular effects but distinct from nitric oxide-dependent mechanisms.

Pharmacokinetics. B7-33 has a short plasma half-life in vitro serum models (approximately 6 minutes). In vivo half-life is similarly short, suggesting frequent dosing or sustained-release formulations would be required for clinical applications. Research efforts have explored lipidated B7-33 analogs (palmitic acid conjugates) to improve stability while preserving activity.

Animal model effects documented in published preclinical work:

• Reduction in cardiac fibrosis in cardiomyopathy and myocardial infarction models
• Preservation of left ventricular function after cardiac injury
• Anti-fibrotic effects in renal myofibroblast cultures and animal renal injury models
• Anti-fibrotic effects in pulmonary fibrosis animal models
• Endothelium-dependent vasodilation
• Reduction in TGF-beta1 production in fibrotic tissue
• Increased MMP-2 production in cardiac and renal fibroblasts

Research-chemical user reports describe subjective improvements in cardiovascular markers (blood pressure, exercise tolerance), claimed effects on recovery from cardiac events, and possible effects on tissue stiffness in fibrosis-related conditions. Reports are anecdotal, uncontrolled, and not verified for vial identity. Self-treatment of cardiovascular disease with research chemicals carries substantial risk.

No standardized human dosing protocol exists for B7-33 because no human clinical trial has been published.

Animal studies have used subcutaneous administration at approximately 0.25 mg/kg/day in mouse cardiomyopathy and MI models. Translation to human equivalents requires pharmacokinetic scaling that has not been performed.

Research-chemical user protocols typically use subcutaneous administration at 200 to 500 mcg per day. These doses are extrapolated from rodent body-surface-area scaling and informal community experience. They are not supported by clinical pharmacokinetic data.

The short half-life (approximately 6 minutes in serum) suggests that practical clinical use would require either multiple daily doses or a sustained-release formulation. Lipidated B7-33 analogs developed for stability improvement are at earlier research stages.

Animal toxicology has not flagged dose-limiting toxicity in published preclinical work. Long-term human safety data does not exist because the compound has not entered human clinical testing.

Theoretical concerns based on mechanism and class:

• Effects on cardiac and vascular function with chronic systemic RXFP1 activation are uncharacterized
• The native relaxin trial program (serelaxin) provided some safety data; B7-33's biased agonism may produce different safety profile
• Drug-drug interactions with ACE inhibitors, ARBs, beta-blockers, antiplatelet agents, and anticoagulants have not been studied
• Effects in pregnancy require careful consideration; relaxin is a pregnancy hormone, and chronic exogenous RXFP1 activation could affect pregnancy outcomes in unpredictable ways
• The serelaxin program documented some adverse events in heart failure populations; whether B7-33 reproduces these is unknown

These concerns are mechanistic flags that Phase 1 safety studies would normally address. Those studies have not occurred.

Self-treatment of cardiovascular or fibrotic disease with research chemicals carries substantial risk. Patients with heart failure, cardiomyopathy, renal disease, or pulmonary fibrosis require evidence-based care under specialist supervision rather than research-chemical experimentation.

B7-33 is in the category of experimental anti-fibrotic peptides without an established research-chemical community for combination protocols. No widely circulated B7-33 stacks exist.

For broader tissue-healing and anti-fibrotic research-chemical category peers:

• BPC-157 and TB-500 for general tissue healing claims (different mechanisms)
• ARA-290 for anti-inflammatory and tissue-protective effects through the innate repair receptor

External pharmaceutical comparators for fibrosis in specific tissues have varied evidence bases:

• For cardiac fibrosis and heart failure: ACE inhibitors, ARBs, ARNI (sacubitril/valsartan), SGLT2 inhibitors, beta-blockers, MRAs (spironolactone, eplerenone) - all with substantial Phase 3 evidence and mortality benefit
• For renal fibrosis and CKD: ACE inhibitors, ARBs, SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin), finerenone - established evidence base
• For pulmonary fibrosis (idiopathic pulmonary fibrosis specifically): Pirfenidone, nintedanib - FDA-approved with substantial Phase 3 evidence

B7-33 has no comparable evidence base and is not a substitute for any of these established therapies in clinically significant fibrotic or heart failure disease. Its scientific interest is in the biased-agonism approach to relaxin pharmacology, which remains an active research area.

For informational and educational purposes only. Not medical advice. Not for human consumption unless prescribed by a licensed physician for an FDA-approved indication. Consult a qualified healthcare provider before using any peptide or pharmaceutical product.