B7-33: A Promising Peptide for In Vitro Cellular and Receptor Research

What is B7-33?

B7-33 is a synthetic peptide derived from the B-chain of human relaxin-2, specifically designed as a single-chain analog that selectively activates the relaxin family peptide receptor 1 (RXFP1) without engaging the receptor’s profibrotic or mitogenic downstream pathways. Unlike native relaxin-2, B7-33 avoids activation of the cAMP pathway and instead triggers the ERK1/2 (extracellular signal-regulated kinase) phosphorylation cascade, making it a biased agonist with unique antifibrotic properties.

This profile makes B7-33 a compelling research candidate for exploring tissue fibrosis, cardiovascular remodeling, and organ protection, particularly in the heart, lungs, kidneys, and liver.

Chemical Structure and Exact Amino Acid Sequence

Chemical Modifications:

• N-terminal or C-terminal modifications (such as acetylation, amidation, or PEGylation) may be employed to enhance stability, receptor affinity, or cellular uptake in experimental settings. 
• Other modifications depend on the synthesis protocol and research applications but are proprietary or tailored per experimental needs.

CAS Number:

Molecular Formula:

Chemical Information

• Molecular Formula: C167H263N49O50S3
• Molecular Weight: ~3870 Da
• CAS Number: 1818415-56-3
• Sequence:

 GRELVRPLRQRLEQLARRRGGGRKRRRR

 (33 amino acids, corresponding to key functional residues from relaxin-2’s B-chain)

• Modifications:
  • Linear peptide with C-terminal amidation (if applicable in synthesis).
  • No disulfide bonds (unlike native relaxin-2).
  • Designed as a monomeric analog of a naturally heterodimeric hormone, increasing its stability and simplifying receptor targeting.

Mechanisms of Action

B7-33 functions as a selective RXFP1 receptor agonist. While native relaxin-2 activates both the cAMP and ERK1/2 pathways, B7-33 shows a biased signaling profile by preferentially activating ERK1/2 without significantly raising cAMP. This selective mechanism is crucial in:

• Promoting matrix metalloproteinase (MMP) expression (e.g., MMP-2), which degrades extracellular matrix components.
• Inhibiting TGF-β1-induced fibroblast-to-myofibroblast differentiation.
• Reducing collagen deposition and tissue fibrosis.
• Exhibiting cardioprotective and anti-remodeling effects without undesired cell proliferation.

Current Research & Applications

Preclinical and in vitro studies suggest B7-33 has promising utility in:

• Cardiac fibrosis and heart failure; Shown to reduce collagen accumulation and improve heart function in animal models of myocardial infarction and pressure overload.

• Pulmonary and hepatic fibrosis; Inhibits fibrosis pathways in models of idiopathic pulmonary fibrosis and liver injury.

• Renal injury; Demonstrates protection against ischemia-reperfusion injury in kidney tissues.

• Cancer-associated fibroblast modulation; Potential for modulating tumor microenvironments by reducing fibroblast activation.

Future Research & Directions

• Hossain, M.A. et al. (2016).

 “A Single-Chain Derivative of Human Relaxin-2 (B7-33) Modulates Fibrosis via the RXFP1 Receptor.”

 Elife, 5:e24004. https://doi.org/10.7554/eLife.24004

• Chow, B.S.M. et al. (2014).

 “Relaxin Prevents the Development and Progression of Cardiac Fibrosis.”

 Nature Communications, 5:3294.  https://doi.org/10.1038/ncomms4294

• Samuel, C.S. et al. (2017).

 “Relaxin-2 and its Derivatives in the Treatment of Fibrosis and Heart Failure.”
 Frontiers in Pharmacology, 8:146.  https://doi.org/10.3389/fphar.2017.00146

References & Further Reading

B7-33 holds significant promise for further exploration in:

• Antifibrotic therapies targeting systemic sclerosis, liver cirrhosis, and fibrotic lung diseases.
• Cardiovascular research including heart failure with preserved ejection fraction (HFpEF).
• Cancer biology to investigate its role in reversing stromal fibrosis.
• Organ transplantation and wound healing, leveraging its tissue remodeling capabilities.

Its biased receptor agonism opens new opportunities for dissecting GPCR signaling and designing tissue-selective peptide therapeutics.

Disclaimer

This product is intended for research purposes only. It is not approved for human or veterinary use, nor is it intended for clinical, diagnostic, or therapeutic applications. All research must comply with applicable local laws and institutional guidelines. Misuse of this compound for human consumption is strictly prohibited.