B7-33
B7-33 research profile covering evidence quality, proposed mechanisms, safety considerations, regulatory status, and linked primary sources.
Evidence-led profile
Research snapshot
- Evidence stage
- Emerging research
- References
- 6 linked sources
- Research coverage
- 4 areas
- Editorial review
- Mar 8, 2026
Published by the PepGuide Editorial Team using our research methodology.
Overview
The relaxin family of peptides comprises four structurally related proteins -- relaxin, insulin-like peptide 3 (INSL3), H3-relaxin, and insulin-like peptide 5 (INSL5) -- that signal through two pairs of G protein-coupled receptors: RXFP1/2 and RXFP3/4. H2-relaxin, the primary endogenous ligand for RXFP1, exhibits vasodilatory, anti-inflammatory, antioxidant, and anti-fibrotic properties. It completed Phase II clinical trials for acute heart failure in 2012, representing the first new treatment approach for this condition in two decades.
However, full-length H2-relaxin presents significant limitations: complex disulfide-bonded two-chain structure making synthesis difficult, requirement for intravenous administration, and activation of the cAMP pathway linked to prostate cancer promotion. B7-33 was developed as a simplified, single-chain analogue that overcomes these drawbacks while preserving therapeutic efficacy.
Mechanism of Action
B7-33 binds RXFP1 with high affinity but acts as a biased agonist, preferentially activating the pERK1/2 signaling pathway over cAMP. This biased signaling produces distinct downstream effects:
- RXFP1-AT2R heterodimerization: B7-33 stimulates formation of RXFP1-angiotensin II type 2 receptor heterodimers, activating pERK1/2 signaling
- MMP-2 upregulation: Increased matrix metalloproteinase-2 expression promotes degradation of excess extracellular collagen
- Cell cycle modulation: pERK pathway activation arrests cell cycle progression at G1 phase in RXFP1-expressing cells
- No cAMP stimulation: Absence of cAMP activation eliminates the tumor-promoting effects observed with full-length H2-relaxin in prostate cancer models
The simplified single-chain structure also makes B7-33 substantially easier and less expensive to manufacture than the two-chain H2-relaxin protein.
Research
Anti-Fibrotic Effects
Fibrosis -- the pathological accumulation of extracellular matrix -- underlies organ failure in at least half of all chronic diseases. B7-33 has demonstrated approximately 50% reduction in cardiac fibrosis in rat models of myocardial infarction-induced heart failure, with concomitant improvements in cardiac function and survival. Similar anti-fibrotic efficacy has been observed in mouse models of asthma and lung fibrosis.
Critically, when administered to mice with prostate cancer at doses exceeding those required for anti-fibrotic effects, B7-33 did not promote tumor growth -- confirming that the selective pERK pathway activation avoids the oncogenic risks associated with full-length relaxin.
Preeclampsia
B7-33 acts at RXFP1 to increase VEGF production in cytotrophoblasts, cells critical for establishing maternal-fetal blood flow. By promoting angiogenesis at the maternal-fetal interface, B7-33 may improve placental perfusion in preeclampsia. Lipidated B7-33 derivatives demonstrate extended in vivo half-life without loss of biological activity, potentially enabling subcutaneous or oral administration for this indication.
Anti-Fibrotic Implant Coatings
B7-33 has been incorporated into coatings for implantable medical devices, where sustained release reduced fibrotic capsule thickness by approximately 50% over six weeks. This approach could eliminate the need for systemic anticoagulant or antiplatelet therapy (e.g., aspirin, clopidogrel) currently required with devices such as coronary stents, broadening the eligible patient population.
Vascular Protection
B7-33 replicates the vasoprotective effects of serelaxin (recombinant H2-relaxin) in male Wistar rats. It enhances bradykinin-mediated endothelium-dependent relaxation by boosting endothelium-derived hyperpolarization in specific vascular beds. This selective vasorelaxation profile positions B7-33 as a candidate therapeutic for endothelial dysfunction and hypertensive disorders.
Safety and Limitations
B7-33 has demonstrated a favorable preclinical safety profile in multiple animal models. Its biased agonism -- activating pERK but not cAMP -- eliminates the tumor-promoting effects observed with full-length H2-relaxin. No significant adverse effects have been reported in published rodent studies at therapeutic or supratherapeutic doses. Clinical safety data in humans are not yet available.
Common Side Effects
- Blood Pressure Drops:: Potential for hypotension due to its potent vasodilatory properties.
- Injection Site Reaction:: Possible redness, itching, or swelling at the site of administration.
- Hypoglycemia:: Minimal reports suggest potential interactions with glucose metabolism in sensitive users.
Research protocol summary
- Route
- Subcutaneous, Intravenous
These values summarize cataloged research protocols. They are not personal dosing instructions or medical guidance.
Reconstitution Calculator
Pharmacokinetic Profile
B7-33 — Pharmacokinetic Curve
Subcutaneous, IntravenousMolecular Structure
- PubChem CID
- 318164840
Research Protocols
subcutaneous Injection
Lipidated B7-33 derivatives demonstrate extended in vivo half-life without loss of biological activity, potentially enabling subcutaneous or oral administration for this indication.
intravenous Injection
However, full-length H2-relaxin presents significant limitations: complex disulfide-bonded two-chain structure making synthesis difficult, requirement for intravenous administration, and activation of the cAMP pathway linked to prostate cancer promotion.
oral
Lipidated B7-33 derivatives demonstrate extended in vivo half-life without loss of biological activity, potentially enabling subcutaneous or oral administration for this indication.
Quality Indicators
What to look for
- Multiple peer-reviewed studies available
- Oral administration available
Frequently Asked Questions
References (6)
- [1]Summers RJ. Recent progress in the understanding of relaxin family peptides and their receptors. Br J Pharmacol (2017)
- [2]Hossain MA et al. A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1. Chem Sci (2016)
- [4]Silvertown JD et al. H2 relaxin overexpression increases in vivo prostate xenograft tumor growth and angiogenesis. Int J Cancer (2006)
- [5]
- [1]B7-33, a Functionally Selective Relaxin Receptor 1 Agonist, Attenuates Myocardial Infarction-Related Adverse Cardiac Remodeling in Mice
→ This study found that B7-33 reduces heart damage and scarring after a heart attack by activating specific protective pathways without the side effects of traditional relaxin treatments.
- [2]B7-33 replicates the vasoprotective functions of human gene-2 relaxin
→ Research demonstrates that B7-33 effectively mimics the vascular benefits of human relaxin, promoting blood vessel health and reducing systemic vascular resistance.
Continue researching B7-33
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