B7-33 (Relaxin-2 Analog)

What Is B7-33?

B7-33 is a short, single-chain peptide derived from the B-chain of human relaxin-2 (H2 relaxin) that binds and activates the relaxin receptor RXFP1. Its developers described it as the first functionally selective agonist of RXFP1, a complex G protein-coupled receptor.^[1]

Native H2 relaxin is a two-chain (A and B) peptide hormone held together by three disulfide bonds. It has potent vasodilatory and anti-fibrotic effects, but it is unstable in human serum and difficult to synthesize efficiently.^[2] B7-33 was designed as a B-chain-only analog that keeps the hormone’s anti-fibrotic activity in a simpler molecule.^[1][3]

Published work on B7-33 covers receptor pharmacology, rodent models of heart, lung and vascular disease, biomaterial coatings for implants, central pain signaling and new delivery formats. Every study summarized on this page used cells, isolated tissues or animals; none reports data from human trials.

Chemical Structure and Molecular Identity

B7-33 is a linear peptide based on the H2 relaxin B-chain; it contains no A-chain and therefore none of the interchain disulfide bonds of the native hormone. It was synthesized chemically as a B-chain-only analog of H2 relaxin.^[1]

B7-33 has no PubChem record, so this page does not state a molecular formula, molecular weight or CAS number. Its exact residue sequence is also not given in the abstracts cited here, and it is not reproduced on this page.

Structural follow-up work has focused on two weaknesses of the single-chain design. One 2023 study explored a minimal H2 relaxin scaffold and tried to improve activity with Aib (aminoisobutyric acid) substitution and hydrocarbon stapling, aiming to re-create the helicity present in the native hormone.^[2] Another reported that B7-33 has an in vitro serum half-life of about 6 minutes, and that fatty-acid conjugation with a suitable spacer extended this to about 60 minutes without altering activity.^[4]

Identity at a glance

• Parent hormone: human relaxin-2 (H2 relaxin)
• Format: single chain, B-chain-derived^[1]
• Target receptor: relaxin family peptide receptor 1 (RXFP1)^[1]
• Related single-chain agonist: peptide 5^[3]
• Derivatives studied: lipidated B7-33 analogs^[4] and nanoparticle conjugates^[5]

Research History and Development

B7-33 was first reported in 2016 as the product of structure-activity work aimed at a simpler, more affordable RXFP1 agonist. The developers pointed to the complex insulin-like structure of H2 relaxin as a barrier to preparation and availability, and to its strong cAMP signaling as a possible driver of reported tumor-promoting actions.^[1]

A 2019 review traced the structure-activity relationships of H2 relaxin and human relaxin-3 that led to two single-B-chain agonists, B7-33 and peptide 5, and summarized their effects in cell and animal models.^[3] Later studies extended B7-33 into vascular, cardiac, biomaterial and neuroscience models, and into stabilized and orally delivered formats.

Mechanisms Studied in Research

B7-33 binds RXFP1 but preferentially activates ERK1/2 phosphorylation (pERK) over cAMP signaling in cells that naturally express the receptor, unlike native H2 relaxin, which drives both. This biased signaling profile is the basis for describing it as functionally selective.^[1]

Receptor context

Cell type strongly affects how B7-33 performs. It showed poor affinity and potency in HEK cells engineered to overexpress RXFP1, yet matched H2 relaxin’s potency in fibroblasts that express RXFP1 natively, where it also reproduced the hormone’s anti-fibrotic effects.^[2]

Anti-fibrotic signaling

The 2016 study linked B7-33’s anti-fibrotic actions to activation of RXFP1-angiotensin II type 2 receptor heterodimers. This led to selective downstream pERK1/2 signaling and induction of matrix metalloproteinase-2 (MMP-2), a collagen-degrading enzyme.^[1]

Cardiomyocyte stress pathways

In primary cardiomyocytes from adult mice exposed to simulated ischemia-reoxygenation, B7-33 improved cell survival and lowered GRP78, a marker of endoplasmic reticulum stress. Its reduction of tunicamycin-induced GRP78 depended on ERK1/2.^[8]

Vascular signaling

In rat mesenteric arteries, B7-33 enhanced bradykinin-mediated, endothelium-dependent relaxation by increasing endothelium-derived hyperpolarization, matching the effect of recombinant H2 relaxin (serelaxin).^[6]

Key Findings From Published Studies

In rodent studies, B7-33 reproduced several organ-protective effects of H2 relaxin, most consistently reduced fibrosis, along with cardiac, vascular and pain-related effects. All findings below come from preclinical models.

Organ fibrosis

In the original report, B7-33 prevented or reversed organ fibrosis and dysfunction in three preclinical rodent models of heart or lung disease, with potency similar to H2 relaxin. Unlike H2 relaxin, it did not promote prostate tumor growth in vivo.^[1]

In an isoprenaline-induced cardiomyopathy model in adult male 129sv mice, B7-33 and relaxin equally reduced left ventricular fibrosis, normalized left ventricular inflammation and cardiomyocyte hypertrophy, and restored blood vessel density and aortic contractility. The ACE inhibitor perindopril lowered blood pressure, inflammation and vascular rarefaction but did not reduce fibrosis or hypertrophy over the same period.^[10]

Myocardial ischemia-reperfusion

In adult male CD1 mice given 30 minutes of coronary artery ligation followed by reperfusion, B7-33 reduced infarct size compared with vehicle (21.99% versus 45.32%) and preserved fractional shortening (29% versus 23%). At 7 days the fractional shortening gap had widened to 29% versus 20%.^[8]

Vascular function

In male Wistar rats, B7-33 and serelaxin both enhanced endothelium-dependent relaxation in mesenteric arteries but had no overall effect in small renal arteries or the aorta. In isolated mouse mesenteric arteries exposed to placental trophoblast-conditioned media, a model of preeclampsia-like endothelial dysfunction, both peptides prevented the dysfunction.^[6]

Implant encapsulation

Biodegradable PLGA coatings releasing B7-33 retained RXFP1 activity in a reporter cell assay. Coated polypropylene implants placed under the skin of mice showed a 49.2% reduction in fibrous capsule thickness over 6 weeks compared with coatings without the peptide.^[7]

Central pain signaling

In mice with Complete Freund’s Adjuvant-induced inflammatory pain, delivery of H2 relaxin or B7-33 into the brain’s lateral ventricle briefly reduced mechanical and thermal sensitivity of the inflamed paw at 30 minutes. An RXFP1 antagonist blocked the mechanical but not the thermal effect.^[9]

Delivery formats

A 2025 mouse cardiomyopathy study conjugated relaxin and B7-33 to glycine-functionalized iron oxide nanoparticles and compared the longer-term anti-fibrotic effects of the orally delivered conjugates with perindopril.^[5]

Because B7-33 has no PubChem reference record, verifying each lot’s identity and purity against HPLC and mass spectrometry certificates of analysis is essential.

Because B7-33 has no PubChem reference record, verifying each lot's identity and purity against HPLC and mass spectrometry certificates of analysis is essential.

Regulatory and Research Status

B7-33 is an experimental research peptide. It is not approved by the FDA for any use, and no human clinical trial results for it appear in the literature summarized here.

Its parent hormone has reached clinical testing. A 2025 study noted that recombinant relaxin is being clinically evaluated for its cardioprotective effects, including anti-fibrotic effects, in patients with heart failure.^[5] That status applies to recombinant relaxin, not to B7-33.

Open questions for B7-33 remain basic. Its short serum half-life has prompted lipidated analogs, and their developers stated that the lead lipidated molecule still needs pharmacokinetic and pharmacodynamic testing in animals.^[4] Work on minimal, helix-stabilized scaffolds is also ongoing.^[2]