B7-33

Also known as: B7-33, Relaxin B7-33, single-chain relaxin-2 B-chain analog

Evidence: Preclinical

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Overview

Single-chain 27-residue mimetic of the human relaxin-2 B chain that biases RXFP1 signaling toward pERK; reduced cardiac and lung fibrosis in rodent models.

B7-33 is a single-chain 27-residue peptide from the B chain of human relaxin-2 (serelaxin): six residues were cut from the N-terminus of B1-33 and both cysteines replaced with serines to stop dimerization, giving a soluble linear peptide instead of the two-chain, three-disulfide hormone (Hossain 2016). It binds RXFP1 and preferentially activates pERK1/2 over cAMP, the first functionally selective agonist of that receptor. In rodents it prevented or reversed heart and lung fibrosis at relaxin-like potency (0.25 mg/kg/day), cut infarct size in mouse ischemia-reperfusion (22% versus 45%) and matched relaxin for left ventricular fibrosis in isoprenaline cardiomyopathy (Devarakonda 2020; Alam 2023). Unlike relaxin it did not promote prostate tumor growth in mice. No human study is published or registered.

Benefits

Reduced cardiac and lung fibrosis in rodent models at relaxin-equivalent potency; smaller infarct and preserved cardiac function in mouse ischemia-reperfusion (rodent); endothelium-dependent vasodilation matching serelaxin (rat). No human data

Dosing reference

Research dose: 1 to 10 mg: vendor and community range, no published human dose. Animal studies used 0.25 to 0.5 mg/kg/day subcutaneously in mice and a 13.3 mcg/kg IV bolus in rats
Range: 1000 to 10000 mcg, 1x daily

Subcutaneous in research use. Animal dosing was continuous: 0.25 to 0.5 mg/kg/day by implanted osmotic minipump in mice, or a single 13.3 mcg/kg IV bolus in rats. In vitro serum half-life is about 6 min, so a once-daily injection has no published basis. No human pharmacokinetic or safety data exist.

Mechanism

Relaxin-2 acts through RXFP1, a GPCR that couples to both cAMP and ERK1/2. The cAMP arm is linked to the tumor-promoting effects reported for relaxin, so B7-33 was designed to bias signaling: it binds RXFP1 and preferentially phosphorylates ERK1/2 with little cAMP response in cells that express RXFP1 endogenously (Hossain 2016). The antifibrotic effect runs through RXFP1-angiotensin II type 2 receptor heterodimers, driving pERK1/2 and the collagen-degrading enzyme MMP-2. In rat mesenteric artery it enhanced bradykinin-mediated endothelium-dependent relaxation through endothelium-derived hyperpolarization, matching serelaxin at equimolar dose (Marshall 2017). Serum stability is the practical limit: half-life in serum in vitro is about 6 min, which lipidated analogs extend to about 60 min (Praveen 2023).

Evidence

Preclinical: animal or in vitro data only

B7-33 bound RXFP1 and preferentially activated pERK over cAMP, and at 0.25 mg/kg/day subcutaneously prevented or reversed fibrosis and dysfunction in three rodent models of heart and lung disease with potency similar to relaxin, without promoting prostate tumor growth in mice (Hossain et al., 2016)
In mouse myocardial ischemia-reperfusion, B7-33 reduced infarct size (22.0% versus 45.3%, p=0.02) and preserved fractional shortening at 24 h and 7 days (Devarakonda et al., 2020)
In isoprenaline-induced cardiomyopathy in mice, B7-33 at 0.25 mg/kg/day matched relaxin for reducing left ventricular fibrosis, inflammation and hypertrophy, and reduced fibrosis faster than perindopril (Alam et al., 2023)
A single IV bolus of 13.3 mcg/kg in rats reproduced the acute vascular effects of serelaxin in mesenteric artery, and 15 to 30 nM prevented trophoblast-induced endothelial dysfunction in mouse arteries ex vivo (Marshall et al., 2017)
In vitro serum half-life is about 6 min; fatty-acid conjugation extended it to about 60 min in analogs that have not been tested in animals (Praveen et al., 2023)
Human-trial status: none. No trial of B7-33 is published or registered on ClinicalTrials.gov; all data are rodent and in vitro

References

Side effects

No human safety data; effects unknown beyond animal studies. As a relaxin-family agonist, vasodilation with lowered blood pressure and reflex tachycardia are plausible class effects. Purity and identity of research-grade material is an added practical risk.

Storage

Storage: Refrigerate 2-8°C (36-46°F)
Lyophilized: 2+ years at room temp, 3+ years refrigerated
Reconstituted: 28-30 days refrigerated

Pharmacology

Half-life: About 6 min in serum in vitro; no in vivo pharmacokinetic study in any species (Praveen 2023)
Molecular weight: 2986.6 Da
Sequence: VIKLSGRELVRAQIAISGMSTWSKRSL-NH2 (27 aa; relaxin-2 B chain 7-33 with Cys11Ser and Cys23Ser, C-terminal amide)