Peptide Schedule
B7-3326 residuesVIKLSGRELVRAQIAISGMSTWSKRSLEach bubble = one amino acid. Size = residue mass. Color = chemical class.B7-33
Benefits
About B7-33
B7-33 is a synthetic single-chain peptide derived from the B-chain of human relaxin-2 (H2 relaxin). It was first described in 2016 by Hossain et al. at the Florey Institute and Monash University as a simplified alternative to native H2 relaxin, which requires a two-chain, three-disulfide-bond insulin-like structure that is expensive and technically difficult to produce. Despite being a short linear peptide that is largely unstructured in solution, B7-33 adopts the correct conformation upon binding to the relaxin family peptide receptor 1 (RXFP1). It is the first functionally selective agonist of RXFP1 — it preferentially activates the pERK1/2 signaling pathway over the canonical cAMP pathway. This biased signaling profile drives its anti-fibrotic activity while potentially avoiding side effects linked to full receptor activation. In preclinical studies, B7-33 demonstrated anti-fibrotic efficacy matching native H2 relaxin across multiple disease models. In mouse myocardial infarction models (ischemia-reperfusion), B7-33 reduced infarct size from 45.3% to 22.0% (P=0.02) and preserved fractional shortening at 7 days post-MI. In isoprenaline-induced cardiomyopathy, B7-33 reduced left ventricular fibrosis more rapidly than the ACE inhibitor perindopril. It also prevented organ fibrosis in preclinical models of lung disease. B7-33 replicates the vasoprotective effects of serelaxin (recombinant H2 relaxin) in rat mesenteric arteries at equimolar doses and prevented endothelial dysfunction caused by placental trophoblast conditioned media, suggesting potential relevance to preeclampsia. In implant studies, PLGA coatings releasing B7-33 reduced fibrotic capsule thickness by 49.2% over 6 weeks in a subcutaneous mouse model. Critically, B7-33 did not promote prostate tumor growth in vivo — a concern with native relaxin-2, which has been implicated in certain cancer progressions. This selective signaling profile makes B7-33 an attractive research tool for studying relaxin receptor biology without the oncogenic risk associated with full RXFP1 activation.
Who Should Consider B7-33
- Cardiovascular disease researchers studying myocardial fibrosis and post-infarction remodeling
- Investigators studying organ fibrosis (cardiac, pulmonary, renal) and TGF-beta/Smad pathway modulation
- Vascular biology researchers examining endothelial function and NO-mediated vasodilation
- Biomaterials scientists developing anti-fibrotic implant coatings
- Reproductive biology researchers studying preeclampsia and vascular dysfunction in pregnancy models
How B7-33 Works
B7-33 binds to the relaxin family peptide receptor 1 (RXFP1), a leucine-rich repeat-containing G protein-coupled receptor. Unlike native H2 relaxin, which activates both cAMP and pERK1/2 pathways through RXFP1, B7-33 is a functionally selective (biased) agonist that preferentially activates pERK1/2 signaling over cAMP accumulation in cells endogenously expressing RXFP1. The anti-fibrotic mechanism centers on RXFP1 forming heterodimers with the angiotensin II type 2 receptor (AT2R). When B7-33 activates RXFP1-AT2R heterodimers, it triggers downstream signaling through pERK1/2 and associated protein phosphatases. This cascade increases the expression and activity of matrix metalloproteinase-2 (MMP-2), a collagen-degrading enzyme that breaks down excess extracellular matrix. Simultaneously, B7-33 suppresses TGF-beta1/Smad signaling, inhibiting myofibroblast differentiation and new collagen deposition. In vascular endothelium, B7-33 stimulates nitric oxide (NO) production through endothelial NOS activation, leading to smooth muscle relaxation and vasodilation. This accounts for its blood pressure-lowering and vasoprotective effects observed in animal studies. The peptide also reduces endoplasmic reticulum stress and limits cardiomyocyte apoptosis during ischemic injury, contributing to its cardioprotective profile. The biased signaling of B7-33 (pERK1/2 over cAMP) is considered therapeutically advantageous because cAMP-mediated effects have been linked to tumor cell proliferation in prostate cancer models, whereas the pERK1/2 pathway drives the anti-fibrotic actions without this oncogenic risk.
What to Expect
No observable effects expected at this stage; peptide exposure establishing in tissue. Based on animal model timelines.
In mouse MI models, measurable cardioprotection (reduced infarct size, preserved fractional shortening) was evident by day 7 post-treatment.
In cardiomyopathy models, 7 days of B7-33 treatment (days 7-14) reduced left ventricular fibrosis and inflammation, matching the efficacy of native relaxin.
Continued anti-fibrotic remodeling expected with sustained dosing; collagen degradation via MMP-2 upregulation is a gradual process.
In implant studies, 6 weeks of B7-33 release produced a 49% reduction in fibrotic capsule thickness. Maximum anti-fibrotic benefit likely requires sustained multi-week exposure.
Dosing Protocol
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 100mcg | Daily |
| Moderate | 250mcg | Daily |
| Aggressive | 500mcg | Daily |
Note: B7-33 is a preclinical research peptide with no human dosing data. The extremely short in vitro serum half-life (~6 minutes) is a primary limitation — twice-daily subcutaneous dosing (0.25 mg/kg per dose, 12 hours apart) was used in mouse studies. All dosing figures here are extrapolated from rodent models. A lipidated derivative (AcK(PalmGlu)-PEG12-B7-33) extends in vitro half-life to ~60 minutes but remains investigational. Store reconstituted peptide cold and use promptly. This is a research compound only — not for human therapeutic use.
How to Inject B7-33
B7-33 is administered via subcutaneous injection in all published animal studies. Reconstitute lyophilized peptide with bacteriostatic water — for a 2 mg vial, adding 2 mL yields a concentration of 1 mg/mL (1000 mcg/mL). Inject subcutaneously in the abdominal area, rotating injection sites to minimize tissue irritation. In mouse studies, the standard protocol was 0.25 mg/kg twice daily (every 12 hours), reflecting the peptide's very short half-life (~6 minutes in serum). For research purposes, twice-daily dosing is likely necessary to maintain meaningful tissue exposure. Use insulin syringes (29-31 gauge) for accurate dosing at microgram-level volumes. Prepare only the amount needed for immediate use, as reconstituted B7-33 degrades quickly at room temperature. All dosing is extrapolated from rodent data — no human pharmacokinetic studies exist to guide bioavailability or dose scaling.
Cycling Protocol
No established cycling protocol exists for B7-33 in any species. Animal studies used continuous daily dosing for 7-14 day treatment windows (e.g., days 7-14 post-injury in cardiomyopathy models). The 8-on/4-off suggestion is a conservative placeholder based on general peptide cycling conventions. Researchers should follow study-specific dosing timelines.
Pharmacokinetics
Source: In vitro serum half-life of ~6 minutes reported in Hossain et al. 2016 (PMID 30155023) and confirmed by Dantas de Lucas et al. 2023 (PMID 37047588). No in vivo PK data published.
Loading the interactive decay curve.
Side Effects
No human safety data exists for B7-33 — all information is derived from animal models. The primary expected pharmacological effect is vasodilation and blood pressure reduction, which could cause hypotension at higher doses. Native relaxin-2 (serelaxin) in human heart failure trials caused mild nausea, headache, and hypotension, though B7-33 has a distinct signaling profile (biased toward pERK1/2 over cAMP). The very short half-life (~6 min) limits systemic exposure, which may reduce adverse effects but also limits therapeutic window. Theoretical concerns include: injection site reactions with repeated subcutaneous dosing, unknown immunogenicity with chronic administration, and potential off-target effects on RXFP1-expressing tissues (brain, kidney, reproductive organs). The lack of human pharmacokinetic and safety data makes risk assessment speculative. Long-term toxicology studies have not been published.
Contraindications
- Pregnancy and breastfeeding — relaxin signaling plays a role in reproductive physiology; exogenous RXFP1 activation may disrupt normal gestational processes
- Hypotension or concurrent use of antihypertensive medications — B7-33 promotes NO-dependent vasodilation and may cause additive blood pressure reduction
- Active malignancy, particularly hormone-sensitive cancers — although B7-33 did not promote prostate tumor growth unlike native relaxin, the safety profile in cancer contexts is not established
- Severe hepatic or renal impairment — peptide metabolism and clearance pathways are not characterized in compromised organ function
- Known hypersensitivity to relaxin-derived peptides or any component of the formulation
Drug Interactions
- ACE inhibitors and ARBs — B7-33 activates RXFP1-AT2R heterodimers and modulates the renin-angiotensin system; additive hypotensive effects and altered AT2R signaling are possible
- Nitrate medications (nitroglycerin, isosorbide) — B7-33 promotes NO production via eNOS activation; combined use may cause excessive vasodilation and hypotension
- Anticoagulants and antiplatelet agents — MMP-2 upregulation by B7-33 could theoretically affect vascular integrity and bleeding risk, though this interaction is uncharacterized
- Calcium channel blockers — additive blood pressure lowering due to overlapping vasodilatory mechanisms
- Immunosuppressants — unknown interactions; B7-33 modulates inflammatory and fibrotic pathways that may intersect with immunosuppressive drug targets
Storage & Stability
Molecular Profile
Related Peptides
References
- A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1PubMed 30155023
- B7-33 replicates the vasoprotective functions of human relaxin-2 (serelaxin)PubMed 28478069
- B7-33, a Functionally Selective Relaxin Receptor 1 Agonist, Attenuates Myocardial Infarction-Related Adverse Cardiac Remodeling in MicePubMed 32295457
- 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 cardiomyopathyPubMed 36753958
- Coatings Releasing the Relaxin Peptide Analogue B7-33 Reduce Fibrotic EncapsulationPubMed 31713411
- A Lipidated Single-B-Chain Derivative of Relaxin Exhibits Improved In Vitro Serum Stability without Altering ActivityPubMed 37047588
- The anti-fibrotic actions of relaxin are mediated through AT2R-associated protein phosphatases via RXFP1-AT2R functional crosstalk in human cardiac myofibroblastsPubMed 32297670