Abstract & Overview
B7‑33 is a single‑chain peptide analog derived from the B‑chain of human Relaxin‑2, designed to selectively activate the Relaxin family peptide receptor 1 (RXFP1). It is being studied as a simplified and stable model for investigating antifibrotic, cardioprotective, and regenerative mechanisms associated with the Relaxin signaling axis. Unlike native Relaxin‑2, which possesses dual‑chain structural complexity, B7‑33 offers enhanced chemical stability and receptor selectivity. This allows researchers to explore RXFP1‑mediated signaling and tissue remodeling with reduced receptor desensitization and more predictable pharmacodynamic properties.
Molecular Pharmacology
B7‑33 retains the essential receptor‑binding motif of Relaxin‑2’s B‑chain but lacks the A‑chain component, resulting in selective partial agonism of RXFP1. Its streamlined design maintains high receptor affinity while biasing intracellular signaling toward ERK1/2 phosphorylation and nitric oxide (NO) production rather than cAMP accumulation. This signaling bias is critical to its antifibrotic and cardioprotective research effects. Studies indicate that B7‑33 acts through the same receptor pocket as Relaxin‑2 but with a distinct conformational influence on receptor activation kinetics.
Receptor Signaling Pathways
Activation of RXFP1 by B7‑33 initiates complex intracellular cascades involving G‑protein–coupled mechanisms and β‑arrestin–mediated scaffolding. The dominant pathways include PI3K/Akt, ERK1/2, and eNOS activation, leading to nitric oxide synthesis and matrix metalloproteinase (MMP) regulation. These pathways collectively contribute to extracellular matrix (ECM) turnover, fibroblast phenotype modulation, and suppression of profibrotic gene expression. Unlike full Relaxin agonists, B7‑33 minimizes excessive cAMP signaling, which can contribute to receptor desensitization in long‑term models.
Fibrosis and ECM Remodeling Research
B7‑33 is being extensively studied in models of fibrosis involving the heart, lung, liver, and kidney. It demonstrates the ability to reduce collagen I and III synthesis and promote MMP‑2 and MMP‑9 activation, supporting ECM degradation and tissue remodeling. Additionally, it downregulates TGF‑β–induced Smad2/3 phosphorylation, a central node in fibroblast activation and myofibroblast differentiation. These effects position B7‑33 as a valuable compound for studying pathways that limit scar formation and promote regenerative tissue remodeling.
Cardiovascular and Pulmonary Models
In cardiovascular research, B7‑33 enhances endothelial relaxation through eNOS activation and increased nitric oxide bioavailability. It also exerts cardioprotective effects by reducing oxidative stress and promoting adaptive remodeling in myocardial tissue. Pulmonary models reveal reduced fibrotic deposition and improved alveolar architecture following B7‑33 exposure, underscoring its utility in studying pulmonary fibrosis mechanisms. Such findings have expanded its use in cellular and organotypic assays exploring vascular integrity and fibroblast–endothelial cross‑talk.
Comparative Analysis: B7‑33 vs. Relaxin‑2
While Relaxin‑2 is the natural ligand for RXFP1, its dual‑chain structure presents stability and formulation challenges for experimental use. B7‑33 circumvents these limitations by maintaining receptor activity through a simplified single‑chain sequence. This design allows selective activation of the ERK and PI3K/Akt pathways while avoiding overstimulation of cAMP production. As a result, B7‑33 demonstrates consistent signaling and minimal receptor internalization in long‑term cellular studies, making it an ideal research analog for sustained RXFP1 activation.
Mechanistic Interactions and Cellular Impact
B7‑33 modulates fibroblast behavior by shifting gene expression away from profibrotic markers such as α‑SMA, COL1A1, and CTGF, while promoting antioxidant and cytoprotective pathways. It enhances mitochondrial function, reduces ROS accumulation, and restores redox balance through Nrf2 and HO‑1 activation. This multifaceted regulation provides a deeper understanding of how Relaxin‑pathway modulation may influence both metabolic and structural aspects of cellular homeostasis.
Summary
B7‑33 provides a simplified yet mechanistically rich model for examining RXFP1 receptor biology and antifibrotic signaling. Its receptor bias, stability, and compatibility with cellular and organoid models make it an important research compound for studying fibrosis, ECM remodeling, and tissue protection. By linking NO‑mediated vasorelaxation with MMP‑driven matrix turnover, B7‑33 helps define the integrated pathways of regenerative and antifibrotic cellular behavior in controlled research contexts.
Educational & Research Disclaimer
This article is for educational and scientific research purposes only. No therapeutic claims or usage recommendations are provided. Compounds referenced are not approved for human use and are intended solely for controlled laboratory experimentation.
B7-33 is a single-chain peptide analog derived from the B-chain of human Relaxin-2. It is studied as a biased agonist of the relaxin family peptide receptor 1 (RXFP1) to investigate relaxin pathway signaling without the full dual-chain structure of native relaxin.
Native Relaxin-2 is a two-chain peptide that activates multiple downstream pathways. B7-33 lacks the A-chain and is used to study selective or biased RXFP1 signaling, allowing researchers to isolate specific intracellular pathways (e.g., antifibrotic signaling) while reducing complexity in experimental models.
Research focuses on RXFP1-mediated signaling, including modulation of fibrotic pathways, extracellular matrix remodeling, nitric oxide (NO) signaling, ERK/MAPK activation, and cellular responses relevant to tissue remodeling and vascular biology.
B7-33 enables investigation of relaxin-associated antifibrotic mechanisms with greater signaling specificity. This helps researchers study how RXFP1 activation influences collagen deposition, fibroblast activity, and tissue stiffness in controlled laboratory settings.
No. B7-33 is referenced in preclinical and experimental research only. It is not approved for human or veterinary use and is intended solely for controlled laboratory investigation.
These publications support relaxin/RXFP1 signaling, biased agonism, and antifibrotic pathway research relevant to B7-33:
Apelin : APJ Receptor Signaling, Cardiovascular Regulation, and Metabolic Research Pathways
Follistatin: Myostatin-Regulated Pathways and Advanced Muscle Research
Cardiogen: Short Peptide Bioregulator for Cardiac and Myocardial Tissue Research
ProstaMax : Short Peptide Bioregulator for Prostate Tissue Regulatory Research
