B7-33
Also known as: single-chain relaxin mimetic, relaxin B-chain analogue, single-B-chain derivative of relaxin, H2 relaxin B-chain-only analogue
Single-chain peptide / functionally selective GPCR agonist (RXFP1 agonist)
What it is
B7-33 is a single-chain linear peptide derived from the B-chain of human gene-2 relaxin (H2 relaxin). It binds to the relaxin family peptide receptor 1 (RXFP1) and acts as a functionally selective agonist, preferentially activating the pERK1/2 (extracellular signal-regulated kinase 1/2) pathway over cyclic AMP (cAMP) signaling in cells that endogenously express RXFP1. This bias toward pERK1/2 over cAMP is proposed to underlie its anti-fibrotic effects without the tumor-promoting actions associated with strong cAMP activation seen with H2 relaxin. The anti-fibrotic mechanism involves activation of RXFP1–angiotensin II type 2 receptor heterodimers, inducing downstream pERK1/2 signaling and upregulation of the collagen-degrading enzyme matrix metalloproteinase-2 (MMP-2). In fibroblasts natively expressing RXFP1, B7-33 demonstrates equivalent potency to H2 relaxin despite poor affinity and potency in HEK cells overexpressing RXFP1. B7-33 also reduces endoplasmic reticulum stress in cardiomyocytes by attenuating GRP78 upregulation in an ERK1/2-dependent manner.
Class: Single-chain peptide / functionally selective GPCR agonist (RXFP1 agonist)
What it's studied for
- Anti-fibrotic effects (organ fibrosis — heart, lung, kidney) Mixed
- B7-33 prevented or reversed organ fibrosis and dysfunction in three pre-clinical rodent models of heart or lung disease with similar potency to H2 relaxin. Anti-fibrotic mechanism involves RXFP1–AGTR2 heterodimers, pERK1/2 signaling, and MMP-2 upregulation. PMID 30155023 Hossain MA et al., Chemical Science (2016)
- B7-33 (0.25 mg/kg/day s.c.) equivalently reduced LV fibrosis and normalized ISO-induced LV inflammation and cardiomyocyte hypertrophy compared to RLX in a mouse isoprenaline cardiomyopathy model, and provided more rapid anti-fibrotic effects than perindopril. PMID 36753958 Alam F et al., Biomedicine & Pharmacotherapy (2023)
- B7-33 (0.25 mg/kg/day) prevented renal fibrosis in UUO-injured mice, reducing collagen fiber thickness and collagen-to-tissue cross reticulation ratio, and increasing renal MMP-2 while reducing TIMP-1. PMID 33908676 Bhuiyan S et al., FASEB Journal (2021)
- Orally administered SPION-B7-33 (25 ng/day via oral gavage every 72 h) demonstrated greater anti-fibrotic efficacy than perindopril in mice with established cardiomyopathy over 4 weeks. PMID 41382190 Somanader-Livera DVN et al., Journal of Biomedical Science (2025)
- Cardioprotection and attenuation of adverse cardiac remodeling post-myocardial infarction Animal studies only
- B7-33 significantly reduced infarct size (21.99% vs 45.32%; p=0.02) and preserved fractional shortening (29% vs 23%; p=0.02) vs vehicle in a mouse ischemia-reperfusion model. In vitro, B7-33 (50 and 100 nmol/L) improved cardiomyocyte survival and reduced ER stress markers. PMID 32295457 Devarakonda T et al., Journal of the American Heart Association (2020)
- B7-33 restored blood vessel density and aortic contractility, and normalized ISO-induced cardiomyocyte hypertrophy and LV inflammation in a mouse cardiomyopathy model. PMID 36753958 Alam F et al., Biomedicine & Pharmacotherapy (2023)
- Vasoprotection and endothelium-dependent relaxation Animal studies only
- Equimolar doses of B7-33 replicated the acute vasoprotective effects of serelaxin: enhanced bradykinin-mediated endothelium-dependent relaxation in rat mesenteric arteries via endothelium-derived hyperpolarization, and prevented endothelial dysfunction induced by placental trophoblast conditioned media in mouse mesente PMID 28478069 Marshall SA et al., European Journal of Pharmacology (2017)
- Reduction of foreign body response / fibrotic encapsulation of implants Animal studies only
- PLGA coatings releasing B7-33 produced a 49.2% reduction in fibrotic capsule thickness over 6 weeks following subcutaneous implantation of polypropylene samples in mice. B7-33 retained RXFP1 agonist activity in vitro reporter assays. PMID 31713411 Welch NG et al., ACS Applied Materials & Interfaces (2019)
- Analgesia (central RXFP1 activation in inflammatory pain) Animal studies only
- Intracerebroventricular injection of B7-33 produced a strong but transient reduction in mechanical and thermal sensitivity of the CFA-injected hind paw (at 30 min post-injection) in a mouse model of inflammatory pain. Co-injection of RXFP1 antagonist blocked mechanical but not thermal analgesia. PMID 34159282 Abboud C et al., Pain Reports (2021)
- Suppression of tumor microenvironment (stromal fibrosis and angiogenesis) in cholangiocarcinoma Animal studies only
- B7-33, delivered via cRGD-modified nanovesicles (B7-33-SNPs), induced fibroblast quiescence and synergistically disrupted CAF-angiogenesis crosstalk in subcutaneous xenograft CCA models, achieving 67.7 ± 17.6% tumor growth inhibition (p<0.001 vs PBS). PMID 41430305 Zhang L et al., Journal of Nanobiotechnology (2025)
- Improved serum stability via lipidation (structure-activity relationship studies) In vitro only
- B7-33 has a short in vitro serum half-life (~6 min). Fatty-acid conjugation with appropriate spacer length extended the in vitro half-life to ~60 min without altering activity. PMID 37047588 Praveen P et al., International Journal of Molecular Sciences (2023)
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| subcutaneous (s.c.) | 0.25 mg/kg/day (described as equivalent dose corrected for MW vs RLX 0.5 mg/kg/day) | 7 days (days 7–14 post-injury) | animal | Research PMID 36753958 |
| not explicitly stated (inferred from comparison with relaxin 0.5 mg/kg/day; route not specified in abstract) | 0.25 mg/kg/day | 7 days | animal | Research PMID 33908676 |
| tail vein injection (intravenous) | 13.3 µg/kg (acute bolus) | single dose; vascular function assessed 3 hours later | animal | Research PMID 28478069 |
| ex vivo (mesenteric artery incubation) | 15 nM and 30 nM | ex vivo co-incubation | animal | Research PMID 28478069 |
| in vitro | 50 nmol/L and 100 nmol/L | in vitro (simulated ischemia-reoxygenation) | in_vitro | Research PMID 32295457 |
| intracerebroventricular (i.c.v.) | Not explicitly quantified in abstract (described as injection into lateral cerebral ventricle) | single injection; assessed 30–120 minutes post-injection | animal | Research PMID 34159282 |
| oral gavage | 25 ng/day (as SPION-B7-33) | 4 weeks (days 14–42 post-injury), every 72 h | animal | Research PMID 41382190 |
Tier key: Research = PMID-cited study · [C] = scraped community source · [S] = model-synthesized from aggregate community reports (softer evidence). How we source.
Safety signals
- Very short in vitro serum half-life (~6 minutes for native B7-33), limiting therapeutic window without chemical modification PMID 37047588
- H2 relaxin (parent hormone) promotes prostate tumor growth via cAMP signaling; B7-33 did not promote prostate tumor growth in pre-clinical testing, attributed to its bias toward pERK over cAMP PMID 30155023
- No human safety or toxicity data reported in any of the reviewed abstracts; all in vivo data are from rodent models PMID 30155023
Contraindications
- No specific contraindications are stated in the reviewed abstracts. The reviewed literature does not address human use, so no human contraindication data are available. PMID 30155023
Frequently asked
What is B7-33 and how does it work?
B7-33 is a single-chain synthetic peptide derived from the B-chain of human relaxin-2 (H2 relaxin). It binds to the relaxin family peptide receptor 1 (RXFP1) and acts as a functionally selective agonist, preferentially activating the pERK1/2 signaling pathway over cyclic AMP (cAMP). This bias is thought to underlie its anti-fibrotic effects — specifically via RXFP1–angiotensin II type 2 receptor heterodimers driving MMP-2 upregulation — while potentially avoiding the tumor-promoting effects linked to strong cAMP activation by the parent hormone.
What has B7-33 been studied for?
Based on published pre-clinical research, B7-33 has been studied for: (1) anti-fibrotic effects in heart, lung, and kidney animal models; (2) cardioprotection and reduction of adverse remodeling post-myocardial infarction in mice; (3) vasoprotection and endothelium-dependent relaxation in rodent arteries; (4) reducing fibrotic encapsulation around implanted devices; (5) central analgesia in a mouse inflammatory pain model; and (6) suppression of cancer-associated fibroblast activity in cholangiocarcinoma mouse models. All data are from pre-clinical (animal or in vitro) studies; no human clinical trial data are reported in the reviewed literature.
What dose of B7-33 should I use?
I'm not a medical professional and can't recommend a protocol for you specifically. What research has shown: in animal studies, B7-33 has been administered at doses such as 0.25 mg/kg/day subcutaneously in mice, 13.3 µg/kg as a single intravenous bolus in rats, and 25 ng/day orally as a nanoparticle conjugate in mice. No human dosing data exist in the reviewed literature.
Is B7-33 FDA approved?
The reviewed abstracts do not state any FDA approval status for B7-33. One abstract notes that H2 relaxin (serelaxin, the parent hormone) received 'provisional FDA approval as a treatment for acute heart failure', but this does not apply to B7-33. The regulatory status of B7-33 requires manual verification with current regulatory sources.
Can I take B7-33 orally?
In the reviewed literature, oral administration of B7-33 was only demonstrated when conjugated to glycine-functionalised superparamagnetic iron oxide nanoparticles (SPION-B7-33 at 25 ng/day every 72 h in mice), which allowed circumnavigation of the gut. Oral bioavailability of naked (unconjugated) B7-33 peptide is not addressed in the reviewed abstracts. No human oral administration data exist.
How long does B7-33 last in the body?
The reviewed literature reports that native B7-33 has a very short in vitro serum half-life of approximately 6 minutes. Fatty-acid conjugation (lipidation) with an appropriate spacer extended the in vitro half-life to approximately 60 minutes. In vivo pharmacokinetic data in humans are not available in the reviewed abstracts.
Does B7-33 cause cancer or promote tumor growth?
In contrast to H2 relaxin — whose strong cAMP activation has been associated with tumor-promoting actions — B7-33 did not promote prostate tumor growth in pre-clinical testing, which researchers attributed to its bias toward pERK signaling over cAMP. One study also investigated B7-33 as an agent to inhibit cancer-associated fibroblast activity in cholangiocarcinoma mouse models. However, long-term oncologic safety data in humans are not available in the reviewed abstracts.
Can I stack B7-33 with other peptides or compounds?
I can't recommend combining compounds — that's a prescribing decision. Here's what has been studied individually: B7-33 has been compared (not combined) to perindopril (an ACE inhibitor) and relaxin in animal models of cardiomyopathy and renal fibrosis (PMID 36753958, PMID 33908676). No human combination data exist in the reviewed literature.
Where can I buy B7-33?
I don't recommend vendors or sources. Please consult a licensed provider.
Can B7-33 treat my heart failure or fibrosis?
I can't suggest treatments for medical conditions. Please speak with a licensed healthcare provider. For context: B7-33 has shown anti-fibrotic and cardioprotective effects in pre-clinical animal models, but no human clinical trial data are reported in the reviewed abstracts.
References
- [1] PMID 30155023 — B7-33 prevented or reversed organ fibrosis and dysfunction in three pre-clinical rodent models of heart or lung disease with similar potency to H2 relaxin. Anti
- [2] PMID 36753958 — B7-33 (0.25 mg/kg/day s.c.) equivalently reduced LV fibrosis and normalized ISO-induced LV inflammation and cardiomyocyte hypertrophy compared to RLX in a mouse
- [3] PMID 33908676 — B7-33 (0.25 mg/kg/day) prevented renal fibrosis in UUO-injured mice, reducing collagen fiber thickness and collagen-to-tissue cross reticulation ratio, and incr
- [4] PMID 41382190 — Orally administered SPION-B7-33 (25 ng/day via oral gavage every 72 h) demonstrated greater anti-fibrotic efficacy than perindopril in mice with established car
- [5] PMID 32295457 — B7-33 significantly reduced infarct size (21.99% vs 45.32%; p=0.02) and preserved fractional shortening (29% vs 23%; p=0.02) vs vehicle in a mouse ischemia-repe
- [6] PMID 28478069 — Equimolar doses of B7-33 replicated the acute vasoprotective effects of serelaxin: enhanced bradykinin-mediated endothelium-dependent relaxation in rat mesenter
- [7] PMID 31713411 — PLGA coatings releasing B7-33 produced a 49.2% reduction in fibrotic capsule thickness over 6 weeks following subcutaneous implantation of polypropylene samples
- [8] PMID 34159282 — Intracerebroventricular injection of B7-33 produced a strong but transient reduction in mechanical and thermal sensitivity of the CFA-injected hind paw (at 30 m
- [9] PMID 41430305 — B7-33, delivered via cRGD-modified nanovesicles (B7-33-SNPs), induced fibroblast quiescence and synergistically disrupted CAF-angiogenesis crosstalk in subcutan
- [10] PMID 37047588 — B7-33 has a short in vitro serum half-life (~6 min). Fatty-acid conjugation with appropriate spacer length extended the in vitro half-life to ~60 min without al
- [11] PMID 37628851 — in-prose reference