Overview
B7-33 is a single-chain peptide derived from the B-chain of human relaxin-2 (H2 relaxin), developed in 2016 as a synthetically tractable substitute for the native hormone.
The problem it solves is real. Native H2 relaxin is a two-chain, three-disulfide-bond peptide that is unstable in human serum and difficult and expensive to synthesise. Its recombinant form, serelaxin, attracted major interest for heart failure and fibrosis but is laborious and costly to produce. B7-33 is a single chain with no disulfide pairing problem.
Its pharmacology contains an instructive twist. In HEK cells engineered to overexpress the relaxin receptor RXFP1, B7-33 showed
poor affinity and potency. But in fibroblasts expressing RXFP1 natively, it was equipotent with H2 relaxin and reproduced the hormone's anti-fibrotic effects. A compound can therefore look weak in an overexpression screen and work in the physiologically relevant cell type — receptor density changes the answer.
In vivo, B7-33 has reversed organ fibrosis in numerous preclinical animal studies. A vascular comparison found that an acute bolus of B7-33 replicated serelaxin's effects: both selectively enhanced bradykinin-mediated endothelium-dependent relaxation in rat mesenteric artery by increasing endothelium-derived hyperpolarisation, with no overall effect in small renal artery or aorta. Both also prevented endothelial dysfunction induced by placental trophoblast conditioned media, a preeclampsia model.
No human trial of B7-33 has been published.
What the evidence shows
Separated by study type- HumanClinical trials and human studies
- No published human clinical trials of B7-33.
- AnimalRodent and other animal models
- Reversed organ fibrosis in numerous preclinical animal studies. A single 13.3 µg/kg tail-vein bolus in male Wistar rats enhanced bradykinin-mediated endothelium-dependent relaxation in mesenteric artery three hours later, matching serelaxin at 26.6 µg/kg.
- In vitroCell and tissue studies
- Equipotent with H2 relaxin in fibroblasts natively expressing RXFP1, reproducing anti-fibrotic effects, despite poor affinity and potency in HEK cells overexpressing RXFP1. Prevented endothelial dysfunction induced by placental trophoblast conditioned media in mouse mesenteric arteries at 15–30 nM.
Key studies & findings
2 studies- 1
B7-33 displayed poor affinity and potency in HEK cells overexpressing RXFP1 but was equipotent with H2 relaxin in fibroblasts natively expressing RXFP1, where it reproduced the hormone's anti-fibrotic effects; it reversed organ fibrosis in numerous preclinical animal studies.
- 2
Equimolar B7-33 replicated serelaxin's acute vascular effects in rat mesenteric artery, selectively enhancing bradykinin-mediated endothelium-dependent relaxation via endothelium-derived hyperpolarisation, and both prevented trophoblast-induced endothelial dysfunction.
Benefits & effects
4 documentedReversed organ fibrosis in multiple preclinical animal models
Anti-fibrotic activity equipotent with relaxin-2 in native-RXFP1 fibroblasts
Enhanced endothelium-dependent vasorelaxation in rat mesenteric artery
Prevented trophoblast-induced endothelial dysfunction in a preeclampsia model
Side effects & safety
1 reportedSafety noteResearch compound for laboratory use only. Not approved for human use; no established human safety database outside the trials cited here.
Recorded in the cited literature No human safety data published.
Vascular effects were artery-bed selective, not systemic
Limitations & open questions
No human data whatsoever. The parent molecule's history is a caution rather than an endorsement: recombinant relaxin-2 (serelaxin) attracted substantial clinical investment for acute heart failure, and B7-33's value proposition is largely that it is cheaper to make than a molecule whose own clinical case was not established. The vascular effects reported were selective to mesenteric artery, with no overall effect in renal artery or aorta, so 'vasoprotective' should not be read as a whole-body vasodilatory effect.
Pharmacology
B7-33 is a 33-residue single-chain peptide derived from the B-chain of human relaxin-2. No PubChem entry was retrievable under this name in this session and no human pharmacokinetic data exist. In rats, a single tail-vein bolus at 13.3 µg/kg produced measurable vascular effects three hours after injection, indicating activity persists beyond the plasma residence expected of a small unmodified peptide.
Frequently asked questions
Why does B7-33 look weak in some assays and potent in others?
Receptor density. In HEK cells engineered to overexpress RXFP1 it showed poor affinity and potency, but in fibroblasts expressing RXFP1 at native levels it matched H2 relaxin. Overexpression screens can misrank compounds like this.
Is B7-33 the same as serelaxin?
No. Serelaxin is recombinant human relaxin-2 — a two-chain, three-disulfide peptide. B7-33 is a single chain derived from just the B-chain, designed to be cheaper and easier to synthesise. In rat mesenteric artery, equimolar doses produced comparable vascular effects.
Has B7-33 been tested in people?
No published human trial exists. All evidence is preclinical.
Citations
2 sources- 1
- 2