B7-33 is a single-chain peptide, synthesized in a soluble form and derived from the naturally occurring protein H2-relaxin. This peptide appears to retain the anti-fibrotic properties of relaxin, reportedly without increasing cAMP production. B7-33 studies have suggested that the peptide may promote the phosphorylation of ERK1/2 and enhance the expression of matrix metalloproteinase 2 (MMP2), possibly leading to the breakdown of extracellular collagen.(1)


Protein & Peptide Structural Discussion

H2-relaxin Protein

The H2-relaxin protein is a multifaceted group of proteins consisting of relaxin, H3-relaxin, insulin-like peptide-3, and insulin-like peptide-5, which scientists consider to demonstrate diverse biological actions, including gene regulation and influencing reproductive, musculoskeletal, and cardiovascular systems.(2)

These proteins appear to interact with four different receptors – RXFP-1, RXFP-2, RXFP-3, and RXFP-4 – each appearing to exert specific actions in an organism. 

  • RXFP-1 receptor may influence sperm motility and joint health, and is considered to play a crucial role in pregnancy. 
  • RXFP-2 receptor appears to affect testicular descent.
  • RXFP-3 receptor may play some part in sleep disturbances. 
  • RXFP-4 receptor exhibits potential signs of affecting hunger cycles. 

Given the broad array of receptors involved and the extensive range of theoretical biological action, extensive research has been conducted on the H2-relaxin protein and its analogs, such as the B7-33 peptide, to study their potential mechanisms of action.


B7-33 Peptide

Typically, the relaxin peptide comprises four components – a signal peptide, a B chain, a C chain, and a COOH terminal. Several studies were conducted to replicate these peptide structures; however, they were reportedly highly insoluble and inactive. After extensive research, scientists modified the structure by producing a B chain and elongating the COOH terminal, thereby forming the first ever-soluble analog – B7-33 peptide – in 2016.(2)

B7-33 and Activation of pERK pathway

Research indicates that the B7-33 peptide may activate the pERK pathway, as opposed to the cAMP pathway typically associated with the alleged anti-fibrotic properties of H2-relaxin. 

The activation of the cAMP pathway by H2-relaxin may stimulate the formation of tumors, which is a significant reported impact of relaxin presence.(3) Moreover, the B7-33 peptide appears to exhibit a strong affinity for the RXFP-1 receptors. Binding the peptide to these receptors may induce activation of the pERK pathway, possibly resulting in increased synthesis of MMP-2 matrix metalloproteinase. These enzymes serve to inhibit the scarring of tissues and thus are considered by scientists to be preventative agents in the onset of fibrosis.3


Research Studies on B7-33 Peptide 

B7-33 Peptide and Vasoprotection

Researchers have considered H2 relaxin to be a potent vasoprotective agent, with apparent potential in mitigating heart failure and fibrosis. However, the exogenous production of H2 relaxin is a laborious and expensive process, prompting research into its analog B7-33 peptide.

To investigate this, a study was conducted on male Wistar rats, wherein their tails were presented with either a placebo, H2 relaxin, or B7-33 peptide. After three hours, vasculature functions in the mesenteric artery, renal artery, and abdominal aorta were assessed. While the impacts in the renal artery and abdominal aorta were reportedly insignificant, both B7-33 and H2 relaxin appeared to cause improvement in the vasodilatory properties in the mesenteric artery. 

Furthermore, an additional study was conducted in female mice with experimentally-induced endothelial dysfunction, wherein they were given either B7-33 or H2 relaxin. The findings suggest that both compounds may have possibly mitigated and prevented the further spread of endothelial dysfunction. 

Sarah A. Marshall et al. state, “In conclusion, equimolar doses of B7-33 replicated the acute beneficial vascular effects of serelaxin in rat mesenteric arteries and also prevented endothelial dysfunction induced by placental trophoblast conditioned media in mouse mesenteric arteries. Therefore, B7-33 should be considered as a cost-effective vasoactive therapeutic in cardiovascular diseases.”(5)

B7-33 Peptide and Preeclampsia

Preeclampsia is considered to be a serious pregnancy complication characterized by hypertension in mothers and decreased fetal weight. To explore the potential impact of the B7-33 peptide on preeclampsia, an in vitro clinical study was conducted using the cell culture of cytotrophoblasts (CTBs), cells found in the inner cellular layer of the embryo.

The study presented CTBs with a placebo, marinobufagenin (MBG) steroid, or glucose for 2 days. After the trial, some of these cells were further given a relaxin antagonist, while all cells were presented with the B7-33 compound.

The study’s results indicated that the B7-33 peptide may possibly increase the vascular endothelial growth factor (VEGF) in all cells. Notably, the relaxin antagonist indicated that the compound may have decreased the concentration of VEGF in the cells. These findings suggest that the B7-33 peptide may have the potential to counteract excessive glucose and marinobufagenin levels.(6)

As per researchers Syeda H Afroze et al., ”Both B7-33 and its lipidated derivative mitigate the MBG- and hyperglycemia-induced dysfunction of CTBs by attenuating anti-angiogenic phenotype similar to that seen in preE. Moreover, the B7-33 and its lipidated derivative-induced effect on CTBs are attenuated by a relaxin antagonist.”(6)

B7-33 Peptide and Anti-Fibrosis

Studies have suggested that H2 relaxin may stimulate the spread of carcinogenic cells, which is attributed to its proposed mechanism of action via cAMP activation. Researchers sought to develop a derivative that might exhibit the proposed anti-fibrosis action of H2 relaxin without activating cAMP, which resulted in the B7-33 peptide.

When given to mice with myocardial infarction, the B7-33 peptide appeared to induce a nearly 50% reduction in cardiac tissue fibrosis and improved heart function, which may lead to fewer complications in the long run. This was attributed to the peptide’s potential to increase the concentration of matrix metalloproteinase protein, which is believed to counteract collagen-damaging cells and prevent fibrosis.(7)(8)

In addition, a study was conducted in mice with prostate cancer. B7-33 was presented to the mice to observe any anti-fibrotic action. Remarkably, it was reported that the peptide may have contributed to preventing fibrosis and spreading prostate tumors. This finding suggested that the peptide may act exclusively via the pERK pathway, thereby preventing cell spread without activating cAMP.



B7-33 peptide is a derivative of the H2 relaxin protein, with a structural variation at the COOH terminal. Compared to H2 relaxin, the peptide has been suggested by researchers to exhibit significant potential, like activating the pERK pathway without inducing cAMP activation which may stimulate cancer cell proliferation. 

Additionally, B7-33 may also possibly exhibit anti-fibrotic action and vasoprotective properties, indicating its potential in cardiovascular and lung disfunction. 

NOTE: These products are intended for laboratory research use only. This peptide is not intended for personal use. Please review and adhere to our Terms and Conditions before ordering.



  1. Summers RJ. Recent progress in the understanding of relaxin family peptides and their receptors. Br J Pharmacol. 2017 May;174(10):915-920. doi: 10.1111/bph.13778. PMID: 28447360. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406287/
  2. Nitin A Patil et al, Relaxin family peptides: structure–activity relationship studies, British Pharmacological Society, vol 174 issue 10, published 06 December 2016. https://doi.org/10.1111/bph.13684 
  3. Mohammed Akhter Hossain et al., A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1, Drug Discovery Biology Pharmacology Monash Biomedicine Discovery Institute, Vol 7, 2016. https://research.monash.edu/en/publications/a-single-chain-derivative-of-the-relaxin-hormone-is-a-functionall 
  4. M. A. Hossain et al., “A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1,” Chem. Sci., vol. 7, no. 6, pp. 3805–3819, 2016, doi: 10.1039/C5SC04754D. https://pubs.rsc.org/en/content/articlelanding/2016/sc/c5sc04754d 
  5. Marshall SA, O’Sullivan K, Ng HH, Bathgate RAD, Parry LJ, Hossain MA, Leo CH. B7-33 replicates the vasoprotective functions of human relaxin-2 (serelaxin). Eur J Pharmacol. 2017 Jul 15;807:190-197. doi: 10.1016/j.ejphar.2017.05.005. Epub 2017 May 3. PMID: 28478069. https://pubmed.ncbi.nlm.nih.gov/28478069/ 
  6. S.H Afroze et al., Abstract P3042: Novel Peptide B7-33 and Its Lipidated Derivative Protect Cytotrophoblasts From Preeclampsia Phenotype in a Cellular Model of the Syndrome, 4 Sep 2019. https://doi.org/10.1161/hyp.74.suppl_1.P3042 
  7. Silvertown JD, Ng J, Sato T, Summerlee AJ, Medin JA. H2 relaxin overexpression increases in vivo prostate xenograft tumor growth and angiogenesis. Int J Cancer. 2006 Jan 1;118(1):62-73. https://pubmed.ncbi.nlm.nih.gov/16049981 
  8. Shu Feng, Irina U. Agoulnik, Natalia V. Bogatcheva, Aparna A. Kamat, Bernard Kwabi-Addo, Rile Li, Gustavo Ayala, Michael M. Ittmann and Alexander I. Agoulnik, Relaxin Promotes Prostate Cancer Progression, March 2007. https://clincancerres.aacrjournals.org/content/13/6/1695 
  9. N. Welch et al., Coatings Releasing the Relaxin Peptide Analogue B7-33 Reduce Fibrotic Encapsulation, ACS Applied Materials and Interfaces, Nov 2019. https://www.researchgate.net/publication/337205944_Coatings_Releasing_the_Relaxin_Peptide_Analogue_B7-33_Reduce_Fibrotic_Encapsulation 
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