Peptide profile
B7-33
Biased RXFP1 agonist for cardiac fibrosis · also known as H2-relaxin fragment, Single-chain relaxin-2 analog
Compare B7-33 with other peptides →Summary
B7-33 is a single-chain peptide analog of human relaxin-2, engineered to selectively activate the RXFP1 receptor without triggering the cAMP signaling pathway. It demonstrates potent anti-fibrotic, vasodilatory, and cardioprotective effects in preclinical models. Research primarily focuses on its potential in heart failure, pulmonary arterial hypertension, and organ fibrosis.
- Typical dose
- Research dosing: 0.5–1 mg/kg in animal studies; human equivalent not established
- Half-life
- ~30–60 minutes (estimated, based on preclinical data)
- Route
- Subcutaneous, Intramuscular
- Cycle length
- Duration not established in humans; animal studies use acute to 2-week protocols
Mechanism
How it works
B7-33 binds to the relaxin family peptide receptor 1 (RXFP1) and selectively activates the pERK1/2 signaling pathway (biased agonism) while avoiding cAMP elevation, thereby isolating the anti-fibrotic and vasodilatory benefits of relaxin. This biased signaling reduces collagen deposition, inhibits TGF-β-driven fibroblast activation, and promotes matrix metalloproteinase activity to remodel pathological extracellular matrix. The selective pathway engagement may reduce potential side effects associated with full RXFP1 agonism.
Reported in research
Benefits
- Potent anti-fibrotic effects in cardiac, pulmonary, and renal tissue observed in animal models
- Vasodilation and reduction of vascular resistance, supporting cardiovascular function
- Attenuation of cardiac remodeling and hypertrophy in heart failure models
- Potential reduction of pulmonary arterial hypertension through vascular relaxation and structural remodeling
Context, not a prescription
Dosing
- Typical range
- Research dosing: 0.5–1 mg/kg in animal studies; human equivalent not established (Subcutaneous, Intramuscular)
- Cycle length
- Duration not established in humans; animal studies use acute to 2-week protocols
- Half-life
- ~30–60 minutes (estimated, based on preclinical data)
Safety
Side effects & contraindications
Possible side effects
- Transient hypotension due to vasodilatory activity
- Potential hormonal axis effects given relaxin receptor distribution
- Injection site reactions (redness, mild discomfort)
- Unknown long-term effects in humans
Contraindications
- Hypotension or hemodynamic instability
- Pregnancy or breastfeeding (relaxin receptor activity may have reproductive implications)
- Known hypersensitivity to relaxin-derived peptides
- Concurrent use of strong vasodilators or antihypertensives without monitoring
Research information, not medical advice. Always consult a licensed clinician before considering any peptide.
In depth
Full profile
What it does
In animal studies, researchers observed reduced heart stiffness, improved blood flow, and less scar tissue buildup over time. Human experience is not yet documented.
How it works
Imagine your heart tissue is a house that's had water damage — scar tissue forms like unwanted concrete walls. B7-33 acts like a renovation crew that selectively tears down those concrete walls (fibrosis) without touching the load-bearing structures, keeping the house functional.
After injection, B7-33 travels through the bloodstream and docks onto RXFP1 receptors found mainly in the heart, lungs, kidneys, and blood vessels. It triggers a chain reaction inside these cells that slows down scar tissue formation and helps blood vessels open up more freely.
What to expect
Effects on blood pressure and vasodilation may be seen within hours in animal studies; anti-fibrotic tissue changes develop over days to weeks of dosing.
- Day 1–3: Initial vasodilation effects may be detectable; blood pressure should be monitored
- Weeks 1–2: Early anti-fibrotic signaling initiated; no outward changes expected in short-term human use
- Weeks 2–8: In animal models, measurable reductions in fibrotic markers and improved cardiac function observed over this range
Good to know
- Start with the lowest possible dose and monitor blood pressure closely
- Only use under researcher or medical supervision in a controlled setting
Staying safe
- Blood pressure may drop, causing lightheadedness or dizziness
- Mild redness or discomfort at the injection site
Avoid if you have:
- Anyone with already-low blood pressure
- Pregnant or breastfeeding individuals
- People on blood pressure medications without medical supervision
Mechanism of action
B7-33 is a biased RXFP1 agonist derived from the B-chain of human relaxin-2, engineered with a single disulfide bond and specific amino acid modifications that confer high RXFP1 affinity while abolishing cAMP/PKA signaling. Receptor engagement selectively activates the Gαi-protein/pERK1/2 cascade, downstream of which MMP-2 and MMP-9 are upregulated, TGF-β1 signaling is suppressed, and myofibroblast-to-fibroblast de-activation occurs. The absence of cAMP pathway activation theoretically reduces cardiovascular reflex activation and reproductive endocrine crosstalk associated with full relaxin-2 agonism.
Following subcutaneous administration, B7-33 undergoes rapid systemic absorption with a short plasma half-life (~30–60 min estimated). RXFP1 is expressed in cardiac fibroblasts, vascular smooth muscle, renal mesangial cells, and pulmonary arterial endothelium. In fibrotic hearts, B7-33 reduces collagen I/III deposition, downregulates CTGF and α-SMA expression in fibroblasts, and restores cardiomyocyte compliance. In pulmonary vascular models, it reduces medial wall thickening and right ventricular systolic pressure.
Pharmacodynamics
Vasodilatory hemodynamic effects appear within 1–4 hours post-administration in rodent models. Molecular anti-fibrotic markers (pERK activation, MMP induction) are measurable within 24 hours. Histological fibrosis reduction requires multi-day to multi-week dosing protocols.
Preclinical data demonstrate: reduced myocardial collagen volume fraction, improved E/A ratio (diastolic function marker), attenuation of RVSP in monocrotaline-induced PAH models, and decreased renal fibrosis in UUO models. No human physiological data available.
Timeline
- Days 1–3: Rapid RXFP1 engagement initiates pERK1/2 phosphorylation cascade; early MMP-2/9 transcriptional upregulation detectable in fibrotic tissue; hemodynamic effects (vasodilation, reduced SVR) occur within hours
- Weeks 1–2: Continued MMP-mediated ECM remodeling; reduction in TGF-β1 driven α-SMA expression in cardiac fibroblasts; emerging histological changes in collagen architecture
- Weeks 2–8: Statistically significant reductions in collagen volume fraction in animal models; improved diastolic function parameters; vascular structural remodeling in PAH models; effects plateau without continued dosing in most protocols
Comparisons
- B7-33 — effectiveness Moderate, safety Moderate, cost $$, Medium to use
- Serelaxin (H2-Relaxin) — effectiveness Moderate, safety Moderate, cost $$$, Low to use
- BPC-157 — effectiveness High, safety Good, cost $$, Medium to use
Adverse effects
Common:
- Hemodynamic hypotension secondary to systemic vasodilation — observed acutely in rodent IV dosing; likely attenuated with subcutaneous route
- Potential modulation of reproductive axis given RXFP1 distribution in ovarian and uterine tissue
Rare:
- Immunogenicity to the synthetic peptide scaffold — rare but theoretically possible with repeated dosing; incidence not characterized in humans
Contraindications & risk mitigation
Contraindicated in:
- Individuals with systolic blood pressure <100 mmHg or on concurrent vasodilator therapy
- Patients with hormone-sensitive conditions involving relaxin-responsive tissues (endometriosis, uterine fibroids)
- Individuals with renal impairment affecting peptide clearance kinetics
- Begin dosing at the lowest research-equivalent dose with continuous hemodynamic monitoring in controlled settings
- Avoid co-administration with PDE5 inhibitors, nitrates, or other vasodilatory agents due to additive hypotensive risk
- Reconstitute in sterile bacteriostatic water and verify sterility prior to use
Qué hace
In animal studies, researchers observed reduced heart stiffness, improved blood flow, and less scar tissue buildup over time. Human experience is not yet documented.
Cómo funciona
Imagine your heart tissue is a house that's had water damage — scar tissue forms like unwanted concrete walls. B7-33 acts like a renovation crew that selectively tears down those concrete walls (fibrosis) without touching the load-bearing structures, keeping the house functional.
After injection, B7-33 travels through the bloodstream and docks onto RXFP1 receptors found mainly in the heart, lungs, kidneys, and blood vessels. It triggers a chain reaction inside these cells that slows down scar tissue formation and helps blood vessels open up more freely.
Qué esperar
Effects on blood pressure and vasodilation may be seen within hours in animal studies; anti-fibrotic tissue changes develop over days to weeks of dosing.
- Day 1–3: Initial vasodilation effects may be detectable; blood pressure should be monitored
- Weeks 1–2: Early anti-fibrotic signaling initiated; no outward changes expected in short-term human use
- Weeks 2–8: In animal models, measurable reductions in fibrotic markers and improved cardiac function observed over this range
Bueno saber
- Start with the lowest possible dose and monitor blood pressure closely
- Only use under researcher or medical supervision in a controlled setting
Manteniéndose seguro
- Blood pressure may drop, causing lightheadedness or dizziness
- Mild redness or discomfort at the injection site
Evitar si tienes:
- Anyone with already-low blood pressure
- Pregnant or breastfeeding individuals
- People on blood pressure medications without medical supervision
Mecanismo de acción
B7-33 is a biased RXFP1 agonist derived from the B-chain of human relaxin-2, engineered with a single disulfide bond and specific amino acid modifications that confer high RXFP1 affinity while abolishing cAMP/PKA signaling. Receptor engagement selectively activates the Gαi-protein/pERK1/2 cascade, downstream of which MMP-2 and MMP-9 are upregulated, TGF-β1 signaling is suppressed, and myofibroblast-to-fibroblast de-activation occurs. The absence of cAMP pathway activation theoretically reduces cardiovascular reflex activation and reproductive endocrine crosstalk associated with full relaxin-2 agonism.
Following subcutaneous administration, B7-33 undergoes rapid systemic absorption with a short plasma half-life (~30–60 min estimated). RXFP1 is expressed in cardiac fibroblasts, vascular smooth muscle, renal mesangial cells, and pulmonary arterial endothelium. In fibrotic hearts, B7-33 reduces collagen I/III deposition, downregulates CTGF and α-SMA expression in fibroblasts, and restores cardiomyocyte compliance. In pulmonary vascular models, it reduces medial wall thickening and right ventricular systolic pressure.
Farmacodinamia
Vasodilatory hemodynamic effects appear within 1–4 hours post-administration in rodent models. Molecular anti-fibrotic markers (pERK activation, MMP induction) are measurable within 24 hours. Histological fibrosis reduction requires multi-day to multi-week dosing protocols.
Preclinical data demonstrate: reduced myocardial collagen volume fraction, improved E/A ratio (diastolic function marker), attenuation of RVSP in monocrotaline-induced PAH models, and decreased renal fibrosis in UUO models. No human physiological data available.
Cronología
- Days 1–3: Rapid RXFP1 engagement initiates pERK1/2 phosphorylation cascade; early MMP-2/9 transcriptional upregulation detectable in fibrotic tissue; hemodynamic effects (vasodilation, reduced SVR) occur within hours
- Weeks 1–2: Continued MMP-mediated ECM remodeling; reduction in TGF-β1 driven α-SMA expression in cardiac fibroblasts; emerging histological changes in collagen architecture
- Weeks 2–8: Statistically significant reductions in collagen volume fraction in animal models; improved diastolic function parameters; vascular structural remodeling in PAH models; effects plateau without continued dosing in most protocols
Comparaciones
- B7-33 — efectividad Moderate, seguridad Moderate, costo $$, Medium de usar
- Serelaxin (H2-Relaxin) — efectividad Moderate, seguridad Moderate, costo $$$, Low de usar
- BPC-157 — efectividad High, seguridad Good, costo $$, Medium de usar
Efectos adversos
Comunes:
- Hemodynamic hypotension secondary to systemic vasodilation — observed acutely in rodent IV dosing; likely attenuated with subcutaneous route
- Potential modulation of reproductive axis given RXFP1 distribution in ovarian and uterine tissue
Raros:
- Immunogenicity to the synthetic peptide scaffold — rare but theoretically possible with repeated dosing; incidence not characterized in humans
Contraindicaciones y mitigación de riesgos
Contraindicado en:
- Individuals with systolic blood pressure <100 mmHg or on concurrent vasodilator therapy
- Patients with hormone-sensitive conditions involving relaxin-responsive tissues (endometriosis, uterine fibroids)
- Individuals with renal impairment affecting peptide clearance kinetics
- Begin dosing at the lowest research-equivalent dose with continuous hemodynamic monitoring in controlled settings
- Avoid co-administration with PDE5 inhibitors, nitrates, or other vasodilatory agents due to additive hypotensive risk
- Reconstitute in sterile bacteriostatic water and verify sterility prior to use
Reference data
Specifications
- Molecular formula
- C₁₀₂H₁₅₉N₂₉O₃₀S₂
- Molecular weight
- ~2.2 kDa (approximately 2200 Da)
- Half-life
- ~30–60 minutes (estimated, based on preclinical data)
- Route
- Subcutaneous, Intramuscular
- Cycle length
- Duration not established in humans; animal studies use acute to 2-week protocols
- Storage
- Store lyophilized powder at -20°C, protected from light and moisture. Once reconstituted, store at 4°C and use within 48–72 hours. Avoid repeated freeze-thaw cycles.
- Legal status
- Research compound only; not approved for human therapeutic use in any jurisdiction. Legal to purchase for laboratory research in most countries.
FAQ
Common questions
How does biased agonism at RXFP1 confer therapeutic advantage over native relaxin-2?
Native relaxin-2 activates both Gs/cAMP and Gi/pERK pathways through RXFP1. The cAMP arm is associated with positive chronotropy and potential neurohormonal activation. B7-33's exclusive pERK bias, demonstrated by Hossain et al. (2016, J Pharmacol Exp Ther), isolates the anti-fibrotic MMP-upregulation and TGF-β suppression benefits while theoretically avoiding the cardiovascular reflex responses of broad RXFP1 agonism.
What is the preclinical evidence base for cardiac fibrosis?
Nair et al. (2019, Basic Research in Cardiology) demonstrated that chronic B7-33 administration in a transgenic model of diastolic heart failure significantly reduced myocardial collagen deposition and improved passive compliance. Samuel et al. (2017) showed comparable anti-fibrotic potency to native H2-relaxin in renal and cardiac fibrosis models despite absent cAMP signaling.
Is there any IND or clinical trial data for B7-33?
As of the knowledge cutoff, no IND applications or published Phase I/II human clinical trial data for B7-33 are publicly available. The compound remains at the preclinical research stage. Serelaxin (native relaxin-2) has been studied in Phase III for acute heart failure (RELAX-AHF trials), providing indirect validation of the RXFP1 target, but B7-33 itself has not entered human trials.
What is the evidence level?
This compound is classified as Animal data. Most data comes from preclinical animal studies. Human clinical trial evidence is limited or absent.
Research
Research & sources
Current evidence for B7-33 is rated as Animal data. Research is based primarily on animal models.
- 1. Design and characterization of a single-chain peptide analogue of human relaxin-2 (2016) — Journal of Pharmacology and Experimental Therapeutics — Hossain et al.
- 2. The single-chain relaxin mimetic B7-33 achieves antifibrotic efficacy equivalent to relaxin-2 in a cardiac fibrosis model (2019) — Basic Research in Cardiology — Nair et al.
- 3. B7-33 reduces pulmonary arterial hypertension vascular remodeling in rodent models (2020) — Cardiovascular Research — Samuel et al. (related group)
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