B7-33
Also known as: H2 relaxin B-chain analog B7-33, single-chain relaxin mimetic, relaxin-2 B-chain (7-33) peptide
Preclinical research compound; not approved
4 notable studies · 4 references
TLDR
B7-33 is a lab-designed single-chain peptide based on the relaxin-2 B-chain that preferentially activates ERK signaling through the RXFP1 receptor; it reduced fibrosis and heart damage in rodent studies, but it has never been tested in humans and is not approved for any use.
At a Glance
Classification: Synthetic single-chain peptide derived from the B-chain of human relaxin-2 (H2 relaxin); functionally selective (biased) agonist of relaxin family peptide receptor 1 (RXFP1)
B7-33 is a lab-designed peptide made from part of the B-chain of human relaxin-2, a hormone with blood-vessel-widening and anti-scarring (anti-fibrotic) effects. Natural relaxin-2 is a complex two-chain molecule held together by disulfide bonds, which makes it hard and expensive to make. B7-33 is a simpler single chain. Its developers reported that it activates the relaxin receptor RXFP1 in a "biased" way, favoring the ERK pathway over cAMP. All published evidence is preclinical (rodent and cell studies). It has not been tested in humans and is not an approved drug.
What Is B7-33?
Human relaxin-2 (serelaxin as a recombinant drug) → two chains (A and B), three disulfide bonds → activates RXFP1 → cAMP and ERK signaling. B7-33 → single linear chain based on B-chain residues 7-33 → binds RXFP1 and preferentially activates pERK. The design goal was to keep the anti-fibrotic effects while avoiding the strong cAMP signaling that was linked to tumor-promoting effects in animal studies of full relaxin.
What Are Researchers Studying?
Organ fibrosis
In the original study, B7-33 prevented or reversed fibrosis and organ dysfunction in three rodent models of heart or lung disease with potency similar to relaxin-2, and unlike relaxin-2 it did not promote prostate tumor growth in mice.
Heart attack and cardiac remodeling
In mice with ischemia-reperfusion injury, B7-33 roughly halved infarct size (22% vs 45%) and preserved heart pumping function at 7 days. In a mouse model of drug-induced cardiomyopathy, B7-33 kept the heart-protective effects of relaxin and reduced left-ventricular fibrosis faster than the ACE inhibitor perindopril.
Blood vessel function
In rats, a single injection of B7-33 enhanced endothelium-dependent relaxation of mesenteric arteries similarly to serelaxin.
How Does It Work?
B7-33 ↓ RXFP1 (relaxin receptor), reported to act through RXFP1-angiotensin II type 2 receptor heterodimers in fibrosis models ↓ preferential pERK1/2 signaling over cAMP (biased agonism) ↓ increased MMP-2 (a collagen-degrading enzyme), less myofibroblast activity ↓ reduced fibrosis in rodent models.
What Does the Research Show?
Human research
NONE. No human studies of B7-33 were found in PubMed.
Animal research
MODERATE (preclinical): several rodent studies from a small number of collaborating groups show anti-fibrotic, cardioprotective and vascular effects.
In-vitro research
Receptor-signaling studies in RXFP1-expressing cells define its biased pERK signaling.
Notable Studies
A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1
animalJournal: Chemical Science. Design and testing of B7-33. It bound RXFP1 and preferentially activated pERK over cAMP in cells, prevented or reversed organ fibrosis in three rodent heart or lung disease models with potency similar to relaxin-2, worked through RXFP1-AT2R heterodimers and MMP-2, and did not promote prostate tumor growth in vivo.
Limitations: Developer-group study; rodent models; includes in-vitro signaling work; no human data.
View publication →B7-33 replicates the vasoprotective functions of human relaxin-2 (serelaxin)
animalJournal: European Journal of Pharmacology. In male rats, a single IV dose of B7-33 enhanced bradykinin-mediated endothelium-dependent relaxation in mesenteric arteries similar to serelaxin. It also protected mouse arteries ex vivo in a model of preeclampsia-like endothelial dysfunction.
Limitations: Acute vascular-function study; rodent and ex vivo tissue; short exposure.
View publication →B7-33, a Functionally Selective Relaxin Receptor 1 Agonist, Attenuates Myocardial Infarction-Related Adverse Cardiac Remodeling in Mice
animalJournal: Journal of the American Heart Association. In mice with cardiac ischemia-reperfusion, B7-33 reduced infarct size (21.99% vs 45.32%) and preserved fractional shortening at 24 hours and 7 days. In isolated cardiomyocytes it improved survival and reduced the ER-stress marker GRP78 via ERK1/2.
Limitations: Male mice only; short follow-up; preclinical.
View publication →The single-chain relaxin mimetic, B7-33, maintains the cardioprotective effects of relaxin and more rapidly reduces left ventricular fibrosis compared to perindopril in an experimental model of cardiomyopathy
animalJournal: Biomedicine & Pharmacotherapy. In mice with isoprenaline-induced cardiomyopathy, B7-33 given from days 7-14 retained relaxin's cardioprotective effects and reduced left-ventricular fibrosis more rapidly than perindopril.
Limitations: Single mouse model; short treatment window; preclinical.
View publication →What We Still Don't Know
• Any human safety, pharmacokinetic or efficacy data (none published) • Whether the rodent anti-fibrotic effects translate to human heart, lung, kidney or skin fibrosis • Long-term safety, including whether avoiding strong cAMP signaling truly avoids relaxin-associated tumor promotion • Stability and half-life in the body; later work has explored lipidated and nanoparticle versions to extend activity • Independent replication outside the developer collaboration
Related Compounds
Recent publications
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Sources & References
- Hossain MA et al. A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1. Chemical Science. 2016.
- Marshall SA et al. B7-33 replicates the vasoprotective functions of human relaxin-2 (serelaxin). European Journal of Pharmacology. 2017.
- Devarakonda T et al. B7-33, a Functionally Selective Relaxin Receptor 1 Agonist, Attenuates Myocardial Infarction-Related Adverse Cardiac Remodeling in Mice. Journal of the American Heart Association. 2020.
- Alam F et al. The single-chain relaxin mimetic, B7-33, maintains the cardioprotective effects of relaxin and more rapidly reduces left ventricular fibrosis compared to perindopril in an experimental model of cardiomyopathy. Biomedicine & Pharmacotherapy. 2023.
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