reviewed april 2026|next review october 2026|88 physicians psi has verified|49054 published studies
B7-33
B7-33 is a single-chain relaxin peptide analog designed to selectively activate RXFP1, the receptor responsible for relaxin's anti-fibrotic effects, offering a simpler synthetic route than the native two-chain relaxin molecule after serelaxin's Phase III clinical failure.
Evidence landscape: 49054 published studies
Limited published studies. All data from animal models and cell-based assays. No human clinical trials.
- 26 Human
- 133 Animal
- 41 Reviews
- 48854 Other research
Engineered as a simplified single-chain peptide that retains RXFP1 agonist activity without requiring the complex heterodimeric structure of native relaxin-2.
Serelaxin (full-length relaxin-2) failed in the RELAX-AHF-2 Phase III trial for acute heart failure, raising questions about the entire relaxin therapeutic pathway.
All data comes from animal models (animal studies). No human clinical trials have been conducted.
PSI Assessment
The relaxin pathway has a clear biological rationale for treating fibrosis, but the clinical path collapsed when serelaxin failed Phase III. B7-33 represents the next attempt at harnessing this biology with a more practical molecule. It selectively activates RXFP1, the receptor that drives anti-fibrotic signaling, and is simpler to manufacture than the native two-chain protein. Animal models show reduced collagen deposition and improved tissue remodeling. The unresolved question is whether any relaxin-pathway compound can overcome the clinical failure that ended serelaxin's development.
A simplified single-chain relaxin analog with consistent anti-fibrotic effects in animal models. The clinical pathway remains uncertain after serelaxin's Phase III failure.
B7-33 was designed to capture the anti-fibrotic effects of relaxin-2 through selective RXFP1 agonism. In animal models, it reduces collagen deposition and myofibroblast differentiation without activating secondary relaxin receptors. The compound is easier to synthesize, more stable, and avoids the manufacturing challenges of the heterodimeric native protein. Whether these animal-study advantages translate into a viable therapeutic remains undemonstrated.
What the evidence supports
RXFP1 activation with anti-fibrotic signaling demonstrated in cardiac fibroblast models. Animal studies show reduced collagen deposition. The single-chain design offers manufacturing advantages over native two-chain relaxin.
What is not yet established
Efficacy and safety in humans. Whether B7-33 can succeed where serelaxin (full-length relaxin-2) failed in Phase III heart failure trials. Long-term effects of chronic RXFP1 activation. Optimal dosing and delivery for fibrotic indications.
Research Evidence
The findings below cover the RXFP1 activation mechanism, anti-fibrotic effects in animal models, and the context of serelaxin's clinical failure.
Evidence by condition
Evidence dimensions across B7-33's investigated applications. Anti-fibrotic activity has animal data only.
| Condition | Mechanism | Animal evidence | Human evidence | Replication |
|---|---|---|---|---|
| Organ Fibrosis |
B7-33 selectively activates RXFP1 and triggers cAMP accumulation comparable to native relaxin-2 in cell-based assays. It does not activate RXFP2 (relaxin family peptide receptor 2) or secondary relaxin receptors.
Selective receptor engagement is critical because relaxin-2 activates multiple receptors. Isolating RXFP1 agonism may improve the therapeutic profile.
In animal models of cardiac fibrosis, B7-33 reduced collagen deposition and myofibroblast differentiation, consistent with anti-fibrotic activity.
Animal fibrosis models show consistent effects, but the gap between animal models and human fibrotic disease is substantial.
Serelaxin (full-length relaxin-2) failed the RELAX-AHF-2 Phase III trial for acute heart failure, leading Novartis to discontinue development.
The Phase III failure raises questions about whether RXFP1 agonism produces clinically meaningful anti-fibrotic effects in humans, regardless of the molecule used.
26 Human|133 Animal|41 Reviews
View all 49054 indexed studiesHow B7-33 Works
B7-33 is a single-chain peptide analog of relaxin-2 that selectively activates the RXFP1 receptor, triggering anti-fibrotic signaling cascades including reduced collagen synthesis and myofibroblast differentiation.
A simplified single-chain version of relaxin that keeps the anti-scarring benefits.
For a more detailed view of the biology, here is what researchers have observed at the molecular level.
B7-33 mimics the B-chain of relaxin-2, selectively activating RXFP1 to trigger cAMP accumulation and downstream anti-fibrotic signaling. It reduces collagen deposition through suppression of myofibroblast differentiation and TGF-beta-mediated fibrotic pathways. Unlike native relaxin-2 (a heterodimeric A/B chain protein), B7-33 is a single-chain peptide that can be synthesized without disulfide bridge formation between separate chains.
What is B7-33 being studied for?
Researchers are studying B7-33 across several health conditions. Each condition below is labeled with the strength of evidence that exists for that specific use, not for B7-33 overall. This means a compound can have human studies for one condition but only animal data for another.
Organ Fibrosis
·PreclinicalAnimal models demonstrate reduced collagen deposition and anti-fibrotic signaling through RXFP1 activation in cardiac, pulmonary, and renal fibrosis models.
Limitations: All data is from animal studies. Controlled human trials have not been conducted. The serelaxin Phase III failure raises questions about the clinical relevance of RXFP1 agonism in fibrotic disease.
Safety and Regulatory Status
FDA Status: Not FDA-approved. No clinical development program active.
Availability: Research compound only. Not available through any clinical or pharmacy channel.
Class context: Animal studies show favorable tolerability. No human safety data exists. The parent pathway (relaxin) was well tolerated in serelaxin Phase III trials.
No human safety data. Animal studies show favorable tolerability at tested doses. Safety in humans is completely unknown.
Peptide Structure
Technical molecular data for researchers and clinicians.
Questions and Comparisons
Questions the evidence raises for a B7-33 discussion.
Frequently Asked Questions
References
Each citation links to the original study on PubMed, the U.S. National Library of Medicine database.
- 1.Reported the design and characterization of B7-33 as a single-chain relaxin analog that selectively activates RXFP1 signaling while being simpler to manufacture than the native two-chain relaxin-2 protein.Hossain MA et al., 2016 in Chem Sci. View on PubMed
- 2.Explored structure-activity relationships of relaxin receptor signaling that informed understanding of how B7-33 achieves biased agonism at RXFP1 without activating secondary relaxin receptors.Praveen P et al., 2019 in Biochemistry. View on PubMed
- 3.Characterized RXFP1 signaling pathways relevant to single-chain relaxin analogs like B7-33, demonstrating that biased agonism at this receptor can selectively engage anti-fibrotic signaling.Kocan M et al., 2017 in Front Pharmacol. View on PubMed
- 4.Reviewed the anti-fibrotic effects of relaxin-2 and its analogs in cardiac and pulmonary fibrosis models, providing context for B7-33 as a next-generation relaxin therapeutic candidate.Samuel CS et al., 2017 in Sci Rep. View on PubMed
- 5.Phase III trial of the parent molecule serelaxin in acute heart failure. While serelaxin showed early benefit, the subsequent RELAX-AHF-2 trial failed, raising questions about the relaxin pathway that B7-33 aims to address through a different pharmacological approach.Teerlink JR et al., 2013 in Lancet. View on PubMed
Medical Disclaimer
This content is for educational and informational purposes only and does not constitute medical advice. The information presented reflects published research as indexed by PSI and should not be used to make treatment decisions. Always consult a qualified healthcare provider before starting, stopping, or modifying any treatment.