B7-33

What is B7-33?

B7-33 is a 33-residue single-chain peptide derivative of human relaxin-2 (the principal circulating relaxin in adults), designed by Mohammed Akhter Hossain's chemistry group at the Florey Institute of Neuroscience and Mental Health in Melbourne to address the synthesis and stability challenges that have limited native relaxin-2's translational development. Native human relaxin-2 is a two-chain peptide (~6 kDa) with three disulfide bonds (one intrachain in the A-chain plus two interchain A-B disulfides) — a structure that requires complex chemoselective synthesis and produces formulation challenges. The 2016 Hossain Chem Sci paper (PMID 30155023) reported B7-33 as a single-chain derivative retaining the principal RXFP1 receptor-binding pharmacophore in a much simpler chemical scaffold, with documented agonist activity at the relaxin/insulin family receptor RXFP1. The 2017 Marshall Eur J Pharmacol paper (PMID 28478069) reported that B7-33 replicates the vasoprotective functions of human relaxin-2 (serelaxin) in preclinical vascular and cardiac models — supporting B7-33 as a credible single-chain alternative to the two-chain serelaxin product. The 2019 Praveen Mol Cell Endocrinol review (PMID 30641102) consolidated the broader 'single chain peptide agonists of relaxin receptors' class concept that B7-33 anchors. B7-33 has not been clinically developed as a therapeutic. Native relaxin-2 (serelaxin) had its own complicated translational arc — the RELAX-AHF-2 Phase 3 trial in acute heart failure did not demonstrate efficacy on the primary mortality endpoint despite the earlier RELAX-AHF Phase 3 data showing benefit, leading to FDA non-approval of serelaxin for acute heart failure and to the Novartis program's discontinuation. B7-33 sits in research-tier development as a chemically tractable single-chain alternative for relaxin-pathway pharmacology, with applications being explored in fibrotic disease, cardiovascular pathology, and pregnancy-related vascular biology. The peptide is sold through some research-channel sources for laboratory use but has no FDA approval, no validated clinical dosing, and no human safety database. This page is the directory entry for B7-33 specifically; the related Relaxin peptide page covers the parent native peptide's biology and clinical history.

What B7-33 Is Investigated For

B7-33 is a research-peptide class topic, not a clinical therapy. The molecule was designed by Hossain and colleagues at the Florey Institute to address the chemoselective-synthesis and chemical-stability challenges that have constrained native relaxin-2 (serelaxin) drug development. The single-chain scaffold retains principal RXFP1 receptor-binding pharmacophore and replicates serelaxin's vasoprotective effects in preclinical models, while being substantially more tractable chemically. The clinical translation of B7-33 has not advanced — partly because the parent serelaxin program failed in the RELAX-AHF-2 Phase 3 acute heart failure trial, weakening the broader relaxin-pathway commercial rationale. B7-33 sits in research-tier development with potential applications in fibrotic disease (the relaxin pathway has antifibrotic effects in some preclinical contexts), cardiovascular pathology (vasodilation, vascular remodeling), and pregnancy-related vascular biology. The peptide is sold through some research-channel sources for laboratory use but has no FDA approval, no validated clinical dosing, no human safety database, and no consumer-research-channel positioning that makes practical sense given the limited evidence base.

History & Discovery

B7-33 was reported in the 2016 Hossain Chem Sci paper (PMID 30155023) from Mohammed Akhter Hossain's chemistry group at the Florey Institute of Neuroscience and Mental Health in Melbourne, in collaboration with John Wade's group and the broader Australian relaxin research community. The design rationale addressed a long-standing translational problem in relaxin drug development: native human relaxin-2 is a two-chain peptide with three disulfide bonds, requiring complex chemoselective synthesis or recombinant expression with careful folding control. The two-chain scaffold complicates pharmaceutical development, formulation, and manufacturing — limitations that contributed to the difficulties faced by the serelaxin (recombinant native relaxin-2) program at Corthera/Novartis. Hossain's single-chain design strategy aimed to retain the principal B-chain receptor-binding pharmacophore in a substantially simpler chemical scaffold that would be tractable for pharmaceutical development. The 2017 Marshall Eur J Pharmacol paper (PMID 28478069) extended the work by demonstrating that B7-33 replicates the vasoprotective functions of native relaxin-2 (serelaxin) in preclinical vascular models — establishing B7-33 as a credible functional alternative rather than just a novel scaffold. The 2019 Praveen Mol Cell Endocrinol review (PMID 30641102) consolidated the broader 'single-chain peptide agonists of relaxin receptors' class concept and characterized structural-activity relationships across single-chain relaxin analogs. The contemporary status (2026) is that B7-33 sits in research-tier development without clinical translation. The broader relaxin-pathway commercial landscape has been substantially complicated by the RELAX-AHF-2 Phase 3 failure of serelaxin in acute heart failure and the subsequent Novartis program discontinuation. Single-chain relaxin alternatives like B7-33 retain medicinal-chemistry interest but lack the commercial momentum that the parent serelaxin program had during its peak development phase. The peptide is sold through some research-channel sources for laboratory use but has no FDA approval, no clinical trials, and no validated consumer-research-channel positioning.

How It Works

B7-33 is a simplified version of human relaxin — a hormone that loosens up tissues and dilates blood vessels (it's why pregnancy involves so much relaxation of joints and ligaments). Native relaxin has two protein chains held together by disulfide bonds, which makes it complicated to manufacture as a drug. B7-33 stitches the relevant parts onto a single chain, making it much easier to make synthetically while still activating the same receptor (RXFP1) and producing the same vasodilation effects in animal studies. It's a research-tier peptide — there are no human trials, no FDA approval, and the parent relaxin drug (serelaxin) failed its Phase 3 heart-failure trial in 2017, which has dampened pharmaceutical interest in the relaxin pathway.

B7-33 is a 33-residue single-chain peptide designed by Hossain and colleagues at the Florey Institute to retain the principal RXFP1 receptor-binding pharmacophore of human relaxin-2 in a chemically tractable single-chain scaffold. Native human relaxin-2 is a two-chain peptide (~6 kDa) consisting of an A-chain (24 residues) and B-chain (29 residues) joined by two interchain disulfide bonds plus one intrachain A-chain disulfide — a structure homologous to insulin and the broader insulin/relaxin superfamily. The two-chain disulfide-bonded structure requires chemoselective synthesis or recombinant expression with proper folding, and produces formulation challenges that have limited pharmaceutical development of native relaxin-2 (commercialized as serelaxin by Corthera/Novartis with regulatory and clinical-trial complications culminating in the RELAX-AHF-2 Phase 3 failure and non-approval). B7-33's single-chain design retains the B-chain core that drives RXFP1 receptor engagement and incorporates an extended single-chain structure that substitutes for the intra/interchain disulfide bonds while preserving receptor-binding geometry. The 2016 Hossain Chem Sci paper (PMID 30155023) reported the single-chain design with documented agonist activity at RXFP1, including cAMP-elevating signaling consistent with native relaxin-2 pharmacology. The 2017 Marshall Eur J Pharmacol paper (PMID 28478069) reported that B7-33 replicates the vasoprotective functions of human relaxin-2 (serelaxin) in preclinical vascular models — supporting B7-33 as a credible single-chain alternative for the relaxin-pathway pharmacology. The 2019 Praveen Mol Cell Endocrinol review (PMID 30641102) consolidated the broader 'single-chain peptide agonists of relaxin receptors' class concept and characterized the structural-activity relationships across the family. Downstream pharmacology of RXFP1 agonism includes vasodilation through nitric oxide and other vasodilator pathways, antifibrotic signaling through modulation of TGF-β-driven fibrotic pathways, pregnancy-related vascular adaptations, and cardiac and vascular remodeling effects. The effects are receptor-mediated rather than direct mechanical; the relaxin name reflects the original observation that the hormone produces relaxation of pregnancy-related tissues (pubic ligament, cervix, uterus) rather than a generalized 'relaxation' of all tissues. The relaxin-pathway has been pursued for fibrotic disease (idiopathic pulmonary fibrosis, scleroderma-associated lung disease — with limited clinical success), acute heart failure (the RELAX-AHF and RELAX-AHF-2 trials of serelaxin — the latter not demonstrating mortality benefit), and various cardiovascular and pregnancy-related applications. The serelaxin program has been substantially discontinued, and B7-33 remains a research-tier peptide.

Evidence Snapshot

Research Gaps & Open Questions

What the current literature has not yet settled about B7-33:

• 01Whether B7-33 or related single-chain relaxin analogs can advance to clinical translation given the parent serelaxin program's RELAX-AHF-2 failure and the dampened commercial rationale for the relaxin-pathway broadly.
• 02Whether selective RXFP1 agonism via single-chain scaffolds produces clinically meaningful effects in fibrotic disease, cardiovascular pathology, or pregnancy-related vascular indications.
• 03Whether the chemistry advantages of single-chain over two-chain relaxin (synthesis tractability, formulation, stability) translate into pharmacokinetic or pharmacodynamic improvements beyond the manufacturing convenience.
• 04The long-term safety profile of chronic RXFP1 agonism — not characterized in any clinical setting because no relaxin-pathway agonist has reached approval.

Forms & Administration

B7-33 is not formulated or approved as a therapeutic in any jurisdiction. Research applications use synthetic B7-33 for in vitro RXFP1 receptor binding and signaling assays, ex vivo tissue pharmacology, and intraperitoneal or subcutaneous administration in animal vascular and fibrotic disease models. Compounded B7-33 in research-chemical channels has no validated clinical use.

Common Questions

Who B7-33 Is NOT For

Drug & Supplement Interactions

There is no validated human drug-interaction profile for B7-33. Theoretical interactions extrapolate from RXFP1 agonist pharmacology and the serelaxin clinical literature. Concurrent use with antihypertensive medications (diuretics, ACE inhibitors, ARBs, calcium channel blockers, beta-blockers) could produce additive blood-pressure-lowering effects through the vasodilatory mechanism. Concurrent use with antifibrotic drugs in fibrotic disease management could in principle interact through TGF-β-pathway modulation. None of these interactions has been characterized for B7-33 in controlled clinical studies.

Safety Profile

Legal Status

Regulatory status changes over time. Verify current local rules with a qualified professional.

Myths & Misconceptions