B7-33 Research: What Published Studies Have Investigated

What is B7-33?

What is B7-33? It is a synthetic linear peptide derived from the B-chain of human gene-2 relaxin, usually written H2 relaxin. Hossain and colleagues reported its design, synthesis and characterisation in Chemical Science in 2016 (PMID 30155023), describing it as the first functionally selective agonist of the relaxin receptor RXFP1.

The parent molecule is worth understanding first, because everything about B7-33 is a response to the parent’s awkwardness. H2 relaxin is a peptide hormone with an insulin-like architecture: two separate chains, designated A and B, held together by three disulfide bridges. That structure is expensive and difficult to make. The 2016 paper describes the conventional synthetic route as requiring separate reactions for the regioselective formation of each disulfide bond and six purification steps, with low overall yields. A recombinant version of the hormone, serelaxin, reached clinical evaluation in acute heart failure, and the paper notes it was laborious and costly to produce.

B7-33 is what happens when a chemistry group asks whether the A-chain and the disulfides are load-bearing. The answer they report is that for one branch of the receptor’s signalling, they are not.

Discovery and origin in the literature

The receptor came late

Relaxin was described as a hormone long before anything was known about how it acts on a cell. Its receptor was identified only in 2002, when Hsu and colleagues reported in Science (PMID 11809971) that relaxin activates two previously orphan G-protein-coupled receptors, then known as LGR7 and LGR8. The International Union of Basic and Clinical Pharmacology subsequently recommended the current names in a 2006 Pharmacological Reviews nomenclature paper (PMID 16507880): the relaxin family peptide receptors, RXFP1 through RXFP4. RXFP1 is the receptor that H2 relaxin and B7-33 act at, and it is worth registering that the entire molecular pharmacology of this system is roughly twenty years old.

The design, step by step

The 2016 paper states the design logic explicitly, and it is unusually legible for medicinal chemistry:

• Discard the A-chain entirely. The starting point is the B-chain alone. The native B-chain, B1-29, is described in the paper as insoluble — a photograph of two vials in the first figure makes the point.
• Trim the N-terminus, extend the C-terminus. Six residues are removed from the N-terminal end and four residues (KRSL) added at the C-terminal end, giving a chain corresponding to positions 7 to 33 of the extended B-chain — which is where the name comes from.
• Remove the cysteines. The two cysteines at positions B11 and B23 are replaced with isosteric serine residues. The paper reports that this prevented peptide dimerisation and aggregation.

The reported outcome of those three moves is a highly positively charged, freely water-soluble peptide, where the native chain it derives from is not. The paper frames this as the first example of minimising a two-chain cyclic insulin-like peptide to a single-chain linear peptide that retains agonist activity.

Reference data

The chemical record for B7-33 is thinner than for a catalogued hormone, and the table reflects that. A PubChem lookup by name returns no compound entry, so no formula, canonical molecular weight or CAS number is listed here — those fields are omitted rather than estimated. What is available is the mass reported by the originating laboratory for its own synthetic material.

Two of those rows deserve to be read together. The binding affinity is roughly an order of magnitude below the parent hormone; the cAMP potency is roughly five orders of magnitude below it. That gap is not a defect in the data — it is the entire point of the molecule, and the next section explains why. No reconstitution procedure, quantity or route is given or implied on this page.

Mechanisms researchers have examined

• Biased agonism at RXFP1 — the central mechanism. RXFP1 couples to multiple downstream pathways, of which cAMP accumulation and ERK1/2 phosphorylation are the two examined here. Hossain et al. (2016) reported that B7-33 binds the receptor but activates the pERK1/2 branch preferentially over the cAMP branch in cells that express RXFP1 natively. In stably transfected HEK cells the pERK response was itself modest and lower than H2 relaxin’s, which the authors note did not by itself explain the downstream effects they saw in fibroblasts.
• MMP-2 induction in (myo)fibroblasts — matrix metalloproteinase-2 is a collagen-degrading enzyme and the practical readout in most of this work. The 2016 paper reported that B7-33 at 30 nM raised MMP-2 levels in human cardiac and rat renal myofibroblasts to a similar extent as native H2 relaxin, and that the effect was abolished by an RXFP1 antagonist.
• RXFP1–AT2 receptor heterodimers — the same paper reported that the MMP-promoting effect was also blocked by an angiotensin II type 2 receptor antagonist (PD123319), consistent with the receptor pair acting together. This is a mechanistic claim about receptor cross-talk, and it rests on antagonist pharmacology rather than on direct structural evidence.
• Endoplasmic reticulum stress — Devarakonda et al. (2020, J Am Heart Assoc, PMID 32295457) reported that B7-33 reduced tunicamycin-induced upregulation of GRP78 in isolated adult cardiomyocytes in an ERK1/2-dependent manner, connecting the signalling bias to a specific cellular stress pathway.
• Endothelium-dependent relaxation — Marshall et al. (2017, Eur J Pharmacol, PMID 28478069) reported by wire myography that B7-33 selectively enhanced bradykinin-mediated relaxation in rat mesenteric artery by increasing endothelium-derived hyperpolarisation, with no overall effect in small renal artery or abdominal aorta.

Each of those is a measurement in a defined preparation. The vascular selectivity in the fourth point is worth noticing precisely because it is uneven: the same injection that changed one artery bed did nothing measurable in two others.

Research findings by area

Fibrosis models

The 2016 paper reports that B7-33 prevented or reversed organ fibrosis and dysfunction in three pre-clinical rodent models of heart or lung disease, with potency the authors describe as similar to H2 relaxin. This is the finding most often repeated about the compound, and it should be read with its qualifiers attached: rodent models, one laboratory group, and endpoints of collagen and organ function rather than of survival.

Myocardial infarction

Devarakonda and colleagues (2020) subjected adult male CD1 mice to ischaemia–reperfusion by 30-minute ligation of the left anterior descending artery. They reported that B7-33 reduced infarct size (21.99% versus 45.32%, P = 0.02) and preserved fractional shortening on echocardiography (29% versus 23%, P = 0.02) at 24 hours, with the difference in fractional shortening widening by seven days. This group is at Virginia Commonwealth University, with the peptide supplied by the Melbourne chemists — a partial independence that is worth registering.

Vascular function and a preeclampsia model

Marshall et al. (2017) compared a single tail-vein injection of B7-33 with serelaxin in male Wistar rats, and separately co-incubated mouse mesenteric arteries in placental trophoblast conditioned media — an ex-vivo way of inducing endothelial dysfunction of the kind described in preeclampsia. They reported that B7-33 at 15 and 30 nM prevented the development of that dysfunction. The paper’s own conclusion is framed as a therapeutic proposal; the measurement is an ex-vivo vessel response.

An unusual application: implant coatings

Welch and colleagues (2019, ACS Appl Mater Interfaces, PMID 31713411) took a different route entirely, embedding B7-33 in a biodegradable poly(lactic-co-glycolic acid) coating on polypropylene implants to counter the fibrous capsule that forms around implanted devices. Subcutaneous implantation in mice over six weeks gave a reported 49.2% reduction in capsule thickness relative to peptide-free coating. It is a materials-science paper rather than a pharmacology paper, and it is included here because it is one of the clearest demonstrations that the peptide retains RXFP1 activity after formulation.

Chemistry that continued

The originating group has kept working on the scaffold rather than treating it as finished. Praveen et al. (2019, Mol Cell Endocrinol, PMID 30641102) reviewed single-chain agonists of relaxin receptors generally; Praveen et al. (2023, PMID 37047588) reported fatty-acid conjugation at various positions and spacer lengths, raising the in-vitro serum half-life from about six minutes to about sixty; and Handley et al. (2023, PMID 37628851) reported further work towards a minimal potent derivative of relaxin-2. That the group is still trying to make it last longer is itself informative about the parent peptide.

Research models and evidence status

Who has done this work

The chemistry is concentrated: Hossain, Praveen, Wade, Bathgate and colleagues at the Florey Institute and the University of Melbourne appear on essentially every synthesis paper, with Samuel’s group at Monash on the fibrosis pharmacology. The cardiac work (Devarakonda, Salloum) and the coatings work (Welch, Thissen, at CSIRO) come from other institutions, but both used peptide supplied by, and co-authored with, the originating chemists. That is a more distributed picture than several compounds in this library, and it is still not independent replication in the strict sense.

What is not established

There are no registered clinical trials of B7-33 — a ClinicalTrials.gov search returns zero studies. There is no published human pharmacokinetic, safety or tolerability data of any kind. The in-vitro serum half-life of roughly six minutes reported by the originating laboratory is short enough that the relationship between the doses used in rodent studies and any exposure in a larger animal is not something this literature has settled; the lipidation work exists precisely because that is a recognised problem.

The claim that B7-33 avoids the tumour-promoting actions attributed to relaxin rests, so far as indexed sources show, on one orthotopic prostate-tumour experiment in the 2016 paper. That is a single negative result in a single model, and the absence of an effect in one experiment is weaker evidence than the presence of one.

There is also a piece of context that belongs on this page in plain terms. The parent hormone was taken into large human trials as serelaxin, and Metra and colleagues reported in the New England Journal of Medicine in 2019 (PMID 31433919) that serelaxin did not meet its primary endpoints in patients hospitalised for acute heart failure. That result says nothing directly about B7-33, which is a different molecule with a deliberately different signalling profile. It does say that promising rodent fibrosis and haemodynamic data in this receptor system have already failed to translate once, at scale, in humans — and that is exactly the kind of prior a reader should carry into any claim made about the analogue.

Nothing in this literature establishes any property of the supplied research material in a person. This page makes no efficacy, therapeutic, anti-fibrotic, cardioprotective or other use claim of any kind, and the material is supplied for laboratory research use only — not for human or veterinary use.

How to verify this compound yourself

B7-33 is a 27-residue synthetic peptide with no public chemical registry entry, which shifts more weight than usual onto the certificate of analysis:

• Mass-spec identity is the primary check. With no CAS number or PubChem record to cross-reference, the measured mass against the published figure (calculated 2986.59 for [M+H]⁺) is the main independent evidence that the vial holds the peptide named on the label rather than a related B-chain fragment. The originating paper reports masses for several close analogues differing by well under 200 Da — resolvable by mass spectrometry, invisible on a label.
• HPLC purity on a 27-mer is a real measurement. At this length a synthesis accumulates deletion sequences, and the purity figure carries genuine information — unlike on a tripeptide, where a high number is close to automatic. Ask what the impurity profile looks like, not only the headline percentage.
• The serine substitutions matter analytically. B7-33 is defined partly by not containing cysteines at two positions. A cysteine-containing contaminant or a mis-synthesised batch would differ in mass and could differ in aggregation behaviour, which is one reason the solubility described in the literature is a useful sanity check on the material.
• Counter-ion documentation — as with any synthetic peptide, usually trifluoroacetate. This affects net peptide content per unit mass and is a documentation question rather than a purity failure.

See how to read a COA for what each certificate line means, and how to verify peptide purity for how the analytical methods fit together. The exact batch received can be checked on the self-serve verify tool.

Research-grade sourcing and verification

B7-33 is not held in stock. It is listed on our sourcing catalogue as available to order — our supplier lists it, we have not bought it, and material of this kind typically takes about two to three weeks to reach us. For laboratory research use only, it is supplied with a per-batch Certificate of Analysis reporting HPLC purity (%) and mass-spec identity confirmation, verifiable at the lot level. For an adjacent compound in this library also studied in tissue-remodelling contexts, see TB-500 research; for another engineered analogue whose page explains why a designed modification changes what a certificate can prove, see FOXO4-DRI research. This is sourcing and quality-assurance framing only.

Frequently asked questions

Literature cited

1. Hsu SY, Nakabayashi K, Nishi S, et al. “Activation of orphan receptors by the hormone relaxin.” Science. 2002;295(5555):671–674. PMID 11809971. pubmed.ncbi.nlm.nih.gov/11809971 (identification of the relaxin receptor).
2. Bathgate RA, Ivell R, Sanborn BM, et al. “International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides.” Pharmacol Rev. 2006;58(1):7–31. PMID 16507880. pubmed.ncbi.nlm.nih.gov/16507880.
3. Hossain MA, Kocan M, Yao ST, et al. “A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1.” Chem Sci. 2016;7(6):3805–3819. PMID 30155023. pubmed.ncbi.nlm.nih.gov/30155023. The paper that introduces B7-33.
4. Marshall SA, O’Sullivan K, Ng HH, et al. “B7-33 replicates the vasoprotective functions of human relaxin-2 (serelaxin).” Eur J Pharmacol. 2017;807:190–197. PMID 28478069. pubmed.ncbi.nlm.nih.gov/28478069.
5. Praveen P, Kocan M, Valkovic A, et al. “Single chain peptide agonists of relaxin receptors.” Mol Cell Endocrinol. 2019;487:34–39. PMID 30641102. pubmed.ncbi.nlm.nih.gov/30641102.
6. Welch NG, Mukherjee S, Hossain MA, et al. “Coatings Releasing the Relaxin Peptide Analogue B7-33 Reduce Fibrotic Encapsulation.” ACS Appl Mater Interfaces. 2019;11(49):45511–45519. PMID 31713411. pubmed.ncbi.nlm.nih.gov/31713411.
7. Metra M, Teerlink JR, Cotter G, et al. “Effects of Serelaxin in Patients with Acute Heart Failure.” N Engl J Med. 2019;381(8):716–726. PMID 31433919. pubmed.ncbi.nlm.nih.gov/31433919 (the parent hormone’s outcome trial).
8. Devarakonda T, Mauro AG, Guzman G, et al. “B7-33, a Functionally Selective Relaxin Receptor 1 Agonist, Attenuates Myocardial Infarction-Related Adverse Cardiac Remodeling in Mice.” J Am Heart Assoc. 2020;9(8):e015748. PMID 32295457. pubmed.ncbi.nlm.nih.gov/32295457.
9. Praveen P, Wang C, Handley TNG, et al. “A Lipidated Single-B-Chain Derivative of Relaxin Exhibits Improved In Vitro Serum Stability without Altering Activity.” Int J Mol Sci. 2023;24(7):6616. PMID 37047588. pubmed.ncbi.nlm.nih.gov/37047588 (source of the ~6-minute serum half-life).
10. Handley TNG, Praveen P, Tailhades J, et al. “Further Developments towards a Minimal Potent Derivative of Human Relaxin-2.” Int J Mol Sci. 2023;24(16):12670. PMID 37628851. pubmed.ncbi.nlm.nih.gov/37628851.