B7-33
A single-chain 26-amino-acid relaxin analog engineered as a biased RXFP1 agonist to deliver the anti-fibrotic and cardioprotective effects of H2 relaxin in a simpler synthetic form.
B7-33 is a synthetic single-chain peptide developed at the Florey Institute and Monash University to recapitulate the therapeutic activity of endogenous human H2 relaxin while being far cheaper and easier to manufacture than the two-chain recombinant protein. It acts as a functionally selective (biased) agonist of the relaxin family peptide receptor 1 (RXFP1), favoring the ERK1/2 signaling arm associated with anti-fibrotic effects over the classical cAMP pathway. Across rodent and cell-culture models it reduces cardiac and renal fibrosis and preserves organ function, but as of 2026 it remains a preclinical research peptide with no published human trials and no approved use.
Class
Synthetic single-chain 26-amino-acid relaxin analog (biased RXFP1 agonist)
Half-life
Approximately minutes to about one hour in rodent studies; human pharmacokinetics not published.
Routes
Subcutaneous injection
Category
Hormone & Reproductive
Researched benefits
What it's studied for
Anti-fibrotic activity
In cardiac and renal fibroblasts B7-33 reduces TGF-beta-induced myofibroblast differentiation, lowers collagen I and III synthesis and fibrotic markers (alpha-SMA, CTGF), and increases matrix metalloproteinase activity that degrades existing extracellular matrix. This is its most consistent preclinical effect.
Cardiovascular protection
In rodent models of cardiac hypertrophy and heart failure (angiotensin II infusion, pressure overload, isoproterenol cardiomyopathy) B7-33 reduces cardiac fibrosis, preserves or improves cardiac function on echocardiography, and produces favorable hemodynamics similar to full-length relaxin.
Renal protection
In chronic kidney disease and diabetic nephropathy models B7-33 reduces markers of glomerular and tubulointerstitial fibrosis while preserving renal function, consistent with RXFP1 expression on renal fibroblasts and mesangial cells.
Broad organ anti-fibrotic potential
Because RXFP1 is expressed across many tissues, B7-33 has shown anti-fibrotic effects in preclinical models of pulmonary, hepatic, and skin fibrosis, supporting a tissue-general anti-fibrotic phenotype.
Vasodilation
Like native relaxin, B7-33 can promote NO-mediated smooth muscle relaxation and vasodilation, which underlies its hemodynamic effects and its theoretical potential to modestly lower blood pressure.
Improved tissue flexibility and collagen remodeling
By modulating collagen deposition and matrix turnover, B7-33 is theorized to improve tissue flexibility and connective-tissue remodeling, echoing relaxin's natural role in remodeling connective tissue during pregnancy.
Mechanism
How it works
B7-33 works by selectively activating the relaxin family peptide receptor 1 (RXFP1), a G-protein-coupled receptor that physiologically responds to the peptide hormone H2 relaxin. RXFP1 is expressed on cardiac fibroblasts and cardiomyocytes, vascular smooth muscle and endothelial cells, renal fibroblasts and mesangial cells, hepatic stellate cells, pulmonary fibroblasts, and other tissues where relaxin signaling regulates fibrotic and vasodilatory responses. Full-length H2 relaxin couples RXFP1 primarily to Gs, raising cAMP and activating PKA, ERK1/2, PI3K/Akt, and eNOS-driven NO synthesis, producing vasodilation, anti-fibrotic, anti-inflammatory, and cardioprotective effects.
The defining feature of B7-33 is biased agonism: its activation profile favors the ERK1/2 (pERK) signaling arm over the classical cAMP pathway that full-length relaxin activates. Biased agonism describes how different ligands at the same receptor can stabilize distinct receptor conformations and produce different downstream signaling, potentially capturing a desired therapeutic pathway while reducing off-target signaling. For relaxin, the ERK1/2 bias is thought to preserve the anti-fibrotic, cardioprotective effects while reducing engagement of pathways that may be less therapeutically relevant, in theory yielding a cleaner therapeutic window.
Structurally, B7-33 is a single-chain 26-amino-acid peptide that retains the critical receptor-binding residues of the H2 relaxin B-chain but lacks the disulfide bonds and A-chain of the full two-chain hormone. It preferentially engages RXFP1's transmembrane activation domain over the ectodomain, which is believed to underlie its altered signaling bias. Downstream, this reduces fibroblast activation and collagen deposition and increases matrix-degrading enzyme activity across multiple tissues.
Important caveats temper this mechanism. The functional selectivity seen in cellular assays does not always translate cleanly across tissues in vivo, anti-fibrotic efficacy in rodents has historically been difficult to reproduce in human fibrotic disease, and the peptide's short half-life, proteolytic susceptibility, and lack of oral bioavailability constrain its clinical utility. Its rapid clearance is why relaxin-class therapy (serelaxin) was delivered by continuous IV infusion in trials rather than intermittent dosing.
Dosing protocols
Dosing & administration
Dosing reflects protocols reported in research and community literature for educational purposes. It is not medical advice or a recommendation. Most peptides here are not approved for human use.
Reconstitution
Supplied as lyophilized white to off-white powder, typically 5 mg or 10 mg per vial. Bring the vial to room temperature and reconstitute with bacteriostatic water (0.9% benzyl alcohol preserved). A common reconstitution for a 5 mg vial is 2 mL, yielding 2.5 mg/mL (2500 mcg/mL), where a 1000 mcg dose = 0.4 mL (40 units on a U-100 insulin syringe). A 10 mg vial with 2 mL yields 5 mg/mL (5000 mcg/mL), where 1000 mcg = 0.2 mL (20 units). Inject the water slowly down the vial wall, swirl gently (do not shake), inspect for clarity, label with the date, and refrigerate. Reconstituted solution is typically stable 2-4 weeks refrigerated; discard if cloudy, discolored, or containing particulates.
Beginner
- Dose
- 500-1000 mcg per injection
- Frequency
- Once daily or every other day
- Timing
- Morning (allows daytime monitoring for hypotension)
- Duration
- 4-6 week cycles, then a 4-8 week break
- Route
- Subcutaneous
Start at the low end (500 mcg) and hold for 2-3 weeks before titrating. Establish baseline labs (CMP/eGFR, CBC, lipids, HbA1c, BNP/NT-proBNP), blood pressure, and ECG first. Not a substitute for validated cardiovascular therapy.
Intermediate
- Dose
- 1000-2000 mcg per injection
- Frequency
- Daily or every other day
- Timing
- Morning
- Duration
- 6-10 week cycles with 4-8 week off-periods
- Route
- Subcutaneous
For users who completed beginner cycles without adverse effects. Expanded monitoring (monthly labs, home BP, periodic ECG/echo). Combinations with other cardioprotective peptides are sometimes added one at a time.
Advanced
- Dose
- 2000-4000 mcg per injection
- Frequency
- Daily (or continuous with quarterly breaks)
- Timing
- Morning
- Duration
- 8-12 week cycles with 4-8 week off-periods
- Route
- Subcutaneous
Used within comprehensive cardiometabolic/longevity stacks. No evidence that higher doses give proportionally better outcomes; mainly increases cumulative exposure and cost. Requires robust clinical infrastructure and pre-committed stop criteria.
- All B7-33 dosing is extrapolated from rodent pharmacology and self-report community patterns; there is no clinical validation in humans. The vendor 'dose range' label of 10-50 mcg reflects research assay doses, whereas self-experimenters commonly report 500-4000 mcg.
- The most commonly reported single dose in self-report communities is 1000 mcg (1 mg) once daily subcutaneously.
- Subcutaneous injection is the overwhelming route for self-experimenters; oral administration would not work (GI degradation) and the IV infusion used for serelaxin is not appropriate for self-administration.
- Overdose risk is primarily hemodynamic (hypotension, bradycardia); management is supportive and there is no specific antidote.
- Because B7-33 targets cardiovascular biology, baseline labs, blood pressure monitoring, and physician involvement are strongly advised, and it should never replace validated heart failure or blood pressure medications.
Evidence
Research & clinical studies (2)
A single-chain derivative of the relaxin hormone is a functionally selective agonist of the G protein-coupled receptor, RXFP1
Characterized B7-33 as a single-chain relaxin analog that activates RXFP1 with biased agonism favoring the ERK1/2 pathway over cAMP, retaining anti-fibrotic signaling.
PMID 26953257The single-chain relaxin mimetic, B7-33, maintains the cardioprotective effects of relaxin and drives cardiac fibroblast to anti-fibrotic phenotype
Demonstrated that B7-33 reduces cardiac fibrosis and improves cardiac function in rodent heart failure and fibrosis models, extending the anti-fibrotic characterization in vivo.
Combinations
Stacking & blends
Tissue Repair Support
Combine anti-fibrotic and broad tissue-repair coverage
B7-33 targets fibrosis via biased RXFP1 activation while BPC-157 and TB-500 provide broad tissue-protective, anti-inflammatory, and healing effects; used in biohacker recovery protocols with no clinical validation.
Mitochondrial Cardioprotection
Multi-mechanism cardiovascular protection
Humanin and MOTS-c add mitochondrial cytoprotection complementary to B7-33's anti-fibrotic action, diversifying cardioprotective mechanisms.
Collagen Remodeling Pair
Coordinated tissue remodeling and collagen regulation
Both peptides influence collagen dynamics and extracellular matrix remodeling, making them a synergistic pairing for connective-tissue focused protocols.
Cardiometabolic Stack
Address anti-fibrotic and metabolic drivers of cardiovascular disease together
GLP-1/GIP agonists deliver weight loss, glycemic control, and established cardiovascular benefit while B7-33 targets fibrosis; mechanistically coherent for cardiometabolic syndrome but clinically unvalidated in combination.
Safety
Side effects & considerations
Commonly reported effects
Contraindications & cautions
- Acute cardiovascular instability (recent MI within 6 weeks, unstable angina, cardiogenic shock, severe aortic stenosis, obstructive hypertrophic cardiomyopathy, significant uncorrected arrhythmias)
- Decompensated heart failure
- Baseline or symptomatic hypotension / volume depletion
- Severe renal disease (eGFR below 30) or acute kidney injury
- Pregnancy and breastfeeding; discontinue 2-4 weeks before attempting conception
- Children and adolescents
- Active cancer (relaxin signaling implicated in some tumor biology) — consult oncology
- Severe autoimmune disease on immunomodulatory therapy or severe hepatic impairment (relative)
- Known hypersensitivity to peptides or preparation components
- Absence of knowledgeable clinical oversight (infrastructure contraindication)
Human safety is unknown because no trials exist. The most informative comparator is the serelaxin (recombinant H2 relaxin) program, which enrolled thousands of patients and was generally well tolerated — main adverse effects were hypotension, occasional worsening renal function, and infusion-site reactions; that program ended for lack of efficacy, not safety. Theoretical drug interactions include additive hypotension with antihypertensives, diuretics, other vasodilators, nitrates, and PDE5 inhibitors, plus uncharacterized interactions with anticoagulants and NSAIDs. Research-chemical quality (purity, endotoxin, truncated synthesis) is a major practical concern for a 26-amino-acid peptide.
FAQ
B7-33 — common questions
What is B7-33 and how is it related to relaxin?
B7-33 is a single-chain, 26-amino-acid synthetic peptide engineered as a functionally selective agonist of RXFP1, designed to recapitulate the anti-fibrotic and cardioprotective effects of endogenous human H2 relaxin in a simpler, cheaper-to-manufacture form. Developed by the Bathgate lab at the Florey Institute and Monash University, it shows biased agonism at RXFP1, preferentially activating the ERK1/2 pathway over cAMP.
Has B7-33 been tested in humans?
No. As of 2026 there are no published Phase 1 or later trials, no publicly disclosed IND, and no ClinicalTrials.gov entries under B7-33. All evidence comes from cell-culture and rodent studies. Human data on the relaxin class come mainly from serelaxin, which failed its Phase 3 heart failure trial despite promising Phase 2 results.
What is biased agonism and why does it matter for B7-33?
Biased agonism is when different ligands at the same receptor produce different downstream signaling by stabilizing different receptor conformations. B7-33's biased RXFP1 activation favors the ERK1/2 pathway (linked to anti-fibrotic effects) over the cAMP pathway, in theory capturing the desired therapeutic signaling while reducing off-target effects for a better therapeutic index.
What conditions is B7-33 potentially useful for?
Preclinical work has examined B7-33 in cardiac fibrosis and heart failure, renal fibrosis and chronic kidney disease, pulmonary fibrosis, and hepatic fibrosis, with a consistent signature of reduced fibrosis and preserved organ function. Self-experimenters use it for cardioprotective and anti-fibrotic purposes, though none of these applications are clinically validated.
What dose of B7-33 do people typically use?
Self-report community doses range from 500-4000 mcg per subcutaneous injection, usually once daily or every other day. Beginners commonly start at 500-1000 mcg for 4-6 week cycles, intermediate users run 1000-2000 mcg for 6-10 weeks, and advanced users go up to 2000-4000 mcg. These are empirical extrapolations from rodent studies with no human validation.
Why did serelaxin fail, and does that mean B7-33 will fail?
Serelaxin (recombinant H2 relaxin) missed its primary endpoint in the RELAX-AHF-2 Phase 3 acute heart failure trial despite a positive Phase 2. Reasons debated include trial design, dose/duration, patient population, and rodent-to-human biology differences. The failure does not automatically predict B7-33's fate because B7-33 differs in its biased profile, smaller size, and pharmacokinetics, but it shows positive preclinical data does not guarantee clinical efficacy for this class.
What are the main side effects of B7-33?
Human side effects are undocumented since no trials exist. Based on mechanism and the serelaxin experience, the most predictable effects are hypotension and occasionally worsened renal function. Theoretical concerns include effects on reproductive function, increased joint laxity, and impaired fibrosis where it is physiologically protective (e.g., acute wound healing). Injection-site reactions are common.
Can I combine B7-33 with heart failure or blood pressure medications?
Any combination with prescribed cardiovascular medications should be discussed with a cardiologist first. B7-33 has theoretical additive hemodynamic interactions with ACE inhibitors, ARBs, beta blockers, calcium channel blockers, and diuretics. It should never substitute for validated heart failure or blood pressure therapy, and prescribed medications should not be stopped to use it.
