Chemically speaking, B7-33 is a synthetic SARM or selective androgen receptor modulator. Preclinical research has indicated that it may have anabolic potential on skeletal muscle, with mechanisms of action deemed comperable to findings in anabolic steroids, though without reported ancillary downstream impacts. Protein synthesis and muscle development are believed to be stimulated by B7-33, which has been theorized to bind preferentially to androgen receptors in muscle tissue.
The B7-33 peptide, derived from the hormone relaxin, has garnered attention in the scientific community for its potential research relevance in the context of cardiovascular and renal diseases. This article reviews the molecular structure of B7-33 and its mechanism of action and explores its potential in mitigating fibrosis and improving angiogenesis and vasodilation in pathological conditions in animal models.
In addition, studies suggest that its alleged anti-catabolic potential may participate in muscle support, possibly preventing breakdown. B7-33 has a designated status for use and evaluation in laboratory environments only, and is not meant for human consumption or usage.
B7-33 Peptide: What is it?
Chemically speaking, B7-33 is a synthetic SARM or selective androgen receptor modulator. Its chemical name is 4-(2-hydroxyethyl)-2-(3-methoxybenzyl)-N, N-dimethyl benzenesulfonamide. Research into muscle cell proliferation inspired the development of B7-33.
B7-33 is a truncated peptide that mimics the central region of relaxin, which is deemed essential for its interaction with its receptor, RXFP1 (Relaxin/insulin-like family peptide receptor 1). The design of B7-33 incorporates key amino acids that may potentially activate RXFP1, albeit with a focus on enhancing angiogenesis and reducing fibrosis. This section discusses the biochemical potential of B7-33, including its molecular weight, amino acid sequence, and receptor binding affinity.
B7-33 Peptide: Mechanism of Action
Investigations purport that B7-33 may bind specifically to the androgen receptors in skeletal muscle to exert its impacts. Proteins inside cells called androgen receptors bind to androgens like testosterone. Increased protein synthesis and muscle development are hypothesized to result from a cascade of cellular signaling pathways activated when an androgen binds to its receptor.
Findings imply that B7-33 may potentially have a tissue-selective action, in contrast to anabolic steroidal compounds that may universally bind to androgen receptors. This implies that it may have a low affinity for organs like the liver and prostate and a high affinity for skeletal muscle.
Furthermore, B7-33 is theorized to help avoid muscle breakdown due to its anti-catabolic potential. B7-33 is speculated to aid in maintaining and auguring muscle mass by preventing its breakdown and increasing protein synthesis.
The research potential of B7-33 in cardiovascular and renal pathologies is largely attributed to its interaction with RXFP1. Upon binding to this receptor, B7-33 is speculated to kickstart a cascade of intracellular signaling pathways involving cyclic AMP (cAMP) and phosphatidylinositol 3-kinase (PI3K), crucial for its biological impacts. This includes the modulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), which may play pivotal roles in extracellular matrix remodeling, a key factor in the development and progression of fibrosis.
Preclinical Studies and Experimental Data
This section synthesizes data from various preclinical studies investigating the potential of B7-33 on animal models of disease. These studies provide insights into the concentration, efficacy, and observed physiological changes attributed to the B7-33 peptide, focusing specifically on its cardiovascular and renal action.
B7-33 Peptide and Fibrosis
Fibrosis is a hallmark of chronic kidney conditions and heart failure, often leading to organ dysfunction and failure. In animal and cell culture studies, B7-33 has been suggested to mitigate fibrosis by regulating the balance between MMPs and TIMPs, thereby preventing excessive collagen deposition and promoting more favorable tissue remodeling. This section reviews the data from various studies suggesting the anti-fibrotic potential of B7-33 in cardiac and renal fibrosis models.
B7-33 Peptide: Angiogenesis and Vasodilation
Beyond its anti-fibrotic potential, B7-33 is hypothesized to also promote angiogenesis and vasodilation, which are deemed critical in improving blood flow and nutrient delivery to tissues under stress or in a disease state. The peptide has been theorized to enhance the production of nitric oxide (NO) in endothelial cells, a vasodilator. It has also been speculated to induce the expression of vascular endothelial growth factor (VEGF), a major driver of new blood vessel formation. This dual action makes B7-33 a potential candidate for future research in diseases where vascular insufficiency and rigid vasculature are predominant features.
B7-33 Peptide: Tissue
The potential of B7-33 to facilitate tissue repair and regeneration is another critical area of interest. This section discusses the role of B7-33 in promoting endothelial cell function and smooth muscle cell relaxation, which may potentially enhance tissue perfusion and oxygenation—key factors in effective tissue repair. Research indicates that B7-33's possible impact on cellular proliferation and apoptosis, particularly in the context of ischemic injuries and myocardial infarction, should be explored, providing insights into its regenerative potential.
Conclusion
Researchers speculate that the B7-33 peptide may represent a significant advancement in the field of peptide research focused on cardiovascular and renal diseases due to its targeted potential on fibrosis and vascular dysfunction.
References
[i] Devarakonda T, Mauro AG, Guzman G, Hovsepian S, Cain C, Das A, Praveen P, Hossain MA, Salloum FN. B7-33, a Functionally Selective Relaxin Receptor 1 Agonist, Attenuates Myocardial Infarction-Related Adverse Cardiac Remodeling in Mice. J Am Heart Assoc. 2020 Apr 21;9(8):e015748. doi: 10.1161/JAHA.119.015748 . Epub 2020 Apr 16. PMID: 32295457; PMCID: PMC7428518.
[ii] 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.
[iii] Alam F, Gaspari TA, Kemp-Harper BK, Low E, Aw A, Ferens D, Spizzo I, Jefferis AM, Praveen P, Widdop RE, Bathgate RAD, Hossain MA, Samuel CS. The single-chain relaxin mimetic, B7-33, maintains the cardioprotective effects of relaxin and more rapidly reduces left ventricular fibrosis compared to perindopril in an experimental model of cardiomyopathy. Biomed Pharmacother. 2023 Apr;160:114370. doi: 10.1016/j.biopha.2023.114370 . Epub 2023 Feb 6. PMID: 36753958.
[iv] Welch NG, Mukherjee S, Hossain MA, Praveen P, Werkmeister JA, Wade JD, Bathgate RAD, Winkler DA, Thissen H. Coatings Releasing the Relaxin Peptide Analogue B7-33 Reduce Fibrotic Encapsulation. ACS Appl Mater Interfaces. 2019 Dec 11;11(49):45511-45519. doi: 10.1021/acsami.9b17859 . Epub 2019 Dec 2. PMID: 31713411.
[v] Praveen P, Kocan M, Valkovic A, Bathgate R, Hossain MA. Single chain peptide agonists of relaxin receptors. Mol Cell Endocrinol. 2019 May 1;487:34-39. doi: 10.1016/j.mce.2019.01.008 . Epub 2019 Jan 11. PMID: 30641102.
