F tier · safety concern
B7-33 has never been tested in humans: searches of ClinicalTrials.gov and the EU Clinical Trials Register return zero registered studies of any phase, so the entire evidence base is rodent and in vitro. The full-length hormone it mimics failed its definitive 6,545-patient phase 3 (RELAX-AHF-2, both primary endpoints missed) and was refused marketing authorisation by the EMA.
b7-33
B7-33 is a 27-residue linear peptide corresponding to residues 7-29 of the human relaxin-2 (H2 relaxin) B-chain with the two cysteines replaced by serine and a C-terminal KRSL extension, developed at the University of Melbourne / Florey Institute by Hossain, Bathgate, Samuel and colleagues. It is a functionally selective (biased) agonist of the relaxin receptor RXFP1, activating pERK1/2 with only weak cAMP signalling, and reduced fibrosis in rodent cardiac and airway disease models. No human trial of B7-33 has ever been registered or published.
// we supply this one
available as a research reagent
≥ 98% HPLC · lyophilised powder · batch certificate published. Grade F above is our own and is not adjusted because we stock it.
the explanation
B7-33 is a short, simplified copy of part of the pregnancy hormone relaxin, made by Australian academic labs so that a single chain could be produced synthetically instead of the complex two-chain hormone. In mice and rats it reduced scarring (fibrosis) in the heart and lungs. It has never been given to a human being in any registered clinical trial, and the full hormone it copies failed a large heart-failure trial in 6,545 patients.
regulatory status
Unapproved worldwide; no human trial ever registered
B7-33 is not an authorised medicine in the UK, EU, US or any other jurisdiction, and no investigational application, phase 1 study or first-in-human protocol appears in ClinicalTrials.gov or the EU Clinical Trials Register. It exists only as a research reagent sold under research-use-only labelling; the FDA has repeatedly treated such labelling as non-determinative and issued warning letters (e.g. Gram Peptides, 31 March 2026) holding that website marketing establishes human drug intent, making the products unapproved new drugs. An injectable synthetic peptide of this kind cannot lawfully be sold as a dietary supplement or food supplement in the US or UK, and B7-33 has no documented status as a permitted dietary ingredient. For sport, B7-33 is not named individually on the WADA Prohibited List but falls squarely within category S0, which prohibits at all times 'any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use'.
how it works · proposed mechanism
Native H2 relaxin is a two-chain, three-disulfide hormone that is expensive and difficult to synthesise. B7-33 was engineered as the minimal single-chain fragment that still engages RXFP1, a class A GPCR, by truncating the B-chain N-terminus, substituting the two cysteines with isosteric serines to prevent dimerisation and aggregation, and adding a KRSL C-terminal extension. The resulting peptide is a biased agonist rather than a faithful relaxin substitute.
Minimal single-chain RXFP1 ligand
B7-33 corresponds to H2 relaxin B-chain residues 7-29 plus a KRSL extension at positions 30-33, giving 27 residues. Replacing Cys11 and Cys23 with serine removes the peptide's ability to form disulfides, so it is fully linear and disulfide-free. This makes routine solid-phase synthesis feasible where recombinant two-chain relaxin is not.
Biased signalling: pERK1/2 over cAMP
In HEK cells overexpressing RXFP1 B7-33 shows poor binding affinity and weak cAMP potency, yet in native human and rodent myofibroblasts it activates ERK1/2 phosphorylation with efficacy and potency similar to H2 relaxin. This dissociation of the ERK arm from the canonical Gs-cAMP arm is the defining pharmacological claim for the molecule.
Anti-fibrotic and anti-remodelling output
Across rodent models the pERK-biased signal translated into reduced collagen deposition and myofibroblast burden: three models in the 2016 founding paper (rat myocardial infarction, mouse isoproterenol cardiomyopathy, mouse ovalbumin allergic airways disease), attenuated post-infarct remodelling in mice, and faster reduction of left ventricular fibrosis than perindopril in a cardiomyopathy model. Implant coatings releasing B7-33 also reduced fibrotic encapsulation.
Rationale for avoiding the cAMP arm
Relaxin's cAMP-coupled signalling has been linked in the literature to proliferative and tumour-promoting effects, which is the stated motivation for engineering a cAMP-sparing analogue. Consistent with that design intent, the 2016 study reported that B7-33 did not promote prostate tumour growth in vivo. This is a preclinical observation only and is not a substitute for formal carcinogenicity or toxicology work.
what’s reported
evidence shape
7 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
There is no human evidence for B7-33 of any kind - not a phase 1, not a healthy-volunteer PK study, not a case series. ClinicalTrials.gov and the EU Clinical Trials Register both return zero records for the compound, a decade after the founding 2016 Chemical Science paper. Marketing that borrows relaxin's clinical credibility is borrowing from a programme that lost: serelaxin (RLX030), recombinant full-length H2 relaxin, was refused EU marketing authorisation in 2014 and then missed both primary endpoints of RELAX-AHF-2 in 6,545 patients (180-day cardiovascular death 8.7% vs 8.9%, P=0.77; worsening heart failure by day 5 6.9% vs 7.7%, P=0.19). Because B7-33 deliberately signals differently from serelaxin, that failure neither condemns nor validates it - it simply means the receptor's most rigorously tested agonist did not deliver hard outcomes, and B7-33 has no data of its own to argue with. Human dose, exposure, immunogenicity and toxicity are all completely unknown.
key published findings
- B7-33 is a 27-residue linear peptide: H2 relaxin B-chain residues 7-29 with Cys11 and Cys23 replaced by serine, extended C-terminally with KRSL (positions 30-33).
- Developed academically at the University of Melbourne / Florey Institute (Hossain, Bathgate, Wade, Samuel and colleagues), first reported in Chemical Science 2016;7:3805-3819.
- It is a functionally selective RXFP1 agonist, activating ERK1/2 in native myofibroblasts with relaxin-like efficacy while producing only modest to poor cAMP responses.
- Anti-fibrotic activity was reported in three rodent models in the founding paper (rat myocardial infarction, mouse isoproterenol cardiomyopathy, mouse ovalbumin allergic airways disease).
- Independent groups replicated anti-remodelling effects: attenuated post-infarction cardiac remodelling in mice (JAHA 2020) and faster left ventricular fibrosis reduction than perindopril in an experimental cardiomyopathy (Biomed Pharmacother 2023).
- B7-33-releasing implant coatings reduced fibrotic encapsulation in vivo (ACS Appl Mater Interfaces 2019), and B7-33 has been studied in cytotrophoblast and rodent preeclampsia models.
- Zero human studies exist: ClinicalTrials.gov and the EU Clinical Trials Register return no records for B7-33 as of July 2026.
- The parent full-length hormone serelaxin was refused EU marketing authorisation in 2014 and failed phase 3 RELAX-AHF-2 (n=6,545) in 2017, published in NEJM 2019.
limitations of the evidence
- No human pharmacokinetic, pharmacodynamic, dose-ranging or safety data of any description.
- Reported plasma half-life in any species could not be verified from a primary source; long-acting lipidated derivatives are being developed, implying the parent peptide is short-lived, but no number is confirmed.
- B7-33 binds RXFP1 with poor affinity and weak cAMP potency in recombinant systems; the claimed activity depends on native-cell ERK readouts, so the mechanism is assay-context dependent.
- Effect sizes come from small rodent cohorts in academic laboratories, with no independent GLP toxicology, carcinogenicity or reproductive toxicity package in the public record.
- Anti-fibrotic endpoints in the literature are histological and biochemical (collagen, myofibroblast markers), not hard clinical outcomes.
- Preeclampsia and vasoprotection findings are largely cell-culture or conference-abstract level and have not been developed into registered trials.
- Grey-market research-use-only material has no verified identity, purity, endotoxin or sterility standard; vendor-listed chemistry is not equivalent to an analysed certificate for a given lot.
documented safety signals
- No human safety data exist, so no safety signal can be excluded - absence of reported harm reflects absence of human exposure records, not demonstrated tolerability.
- Relaxin-RXFP1 signalling has been linked to proliferative and tumour-promoting effects in the literature, which is the explicit reason B7-33 was engineered to spare the cAMP arm; the 2016 paper reported no promotion of prostate tumour growth in vivo, but no formal carcinogenicity study has been published.
- RXFP1 agonism is vasodilatory and haemodynamically active, and the parent hormone was given by intravenous infusion under monitoring in trials; unsupervised self-administration of an unstudied vasoactive peptide is an unquantified risk.
- Immunogenicity of a non-native, cysteine-substituted, C-terminally extended peptide has never been assessed in humans.
- Products sold as B7-33 are unapproved new drugs; the FDA has issued warning letters (e.g. 31 March 2026) rejecting research-use-only labelling as a defence where marketing establishes human drug intent.
identity
| full name | B7-33 (single-chain analogue of the human relaxin-2 / H2 relaxin B-chain) |
| category | Healing & Repair |
| modality | peptide |
| formula | C131H228N40O37S |
| molar mass | 2987.5 g/mol |
| cas | 1818415-56-3 |
| sequence | VIKLSGRELVRAQIAISGMSTWSKRSL |
laboratory handling
| storage | Lyophilised powder is stored desiccated at -20 °C and protected from light. Reconstituted solution is held at 2-8 °C for short-term laboratory use or aliquoted and frozen; the peptide is linear and disulfide-free, so aggregation on freeze-thaw is less of a concern than for the parent two-chain hormone. Handling information only. |
| solubility | Soluble in sterile or bacteriostatic water; the cysteine-to-serine substitutions remove disulfide-driven aggregation, which is why this analogue exists at all. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
7 citedEuropean Medicines Agency · 2014 · official
Chemical Science · 2016 · preclinical
Journal of the American Heart Association · 2020 · preclinical
Biomedicine & Pharmacotherapy · 2023 · preclinical
International Journal of Molecular Sciences · 2023 · preclinical
ACS Applied Materials & Interfaces · 2019 · preclinical
New England Journal of Medicine · 2019 · randomized
others in Healing & Repair