Human Relaxin-2 is a peptide hormone structurally similar to insulin, composed of two chains (A and B) connected by disulfide bonds. It was originally identified for its role in pregnancy (relaxing pelvic ligaments) but has been extensively studied for cardiovascular applications, particularly acute heart failure. Serelaxin (recombinant relaxin-2) showed promising early results for acute heart failure but failed to meet primary endpoints in the pivotal Phase 3 RELAX-AHF-2 trial, leading Novartis to halt development. Research continues in liver fibrosis, portal hypertension, and HFpEF.
Category: Cardiovascular. Evidence rating: C (early/mixed human evidence).
Clinical status: Phase 3 completed (RELAX-AHF-2 failed primary endpoint). Development halted by Novartis. Research continues in fibrosis indications.
Relaxin-2 activates the relaxin family peptide receptor 1 (RXFP1), a leucine-rich repeat-containing GPCR. RXFP1 activation stimulates adenylyl cyclase via Gs coupling and also activates the PI3K/Akt/eNOS pathway, increasing nitric oxide production. This produces systemic and renal vasodilation,…
Safety considerations: Hypotension from potent vasodilatory effects (dose-limiting); IV infusion site reactions; Potential bradycardia and heart rate changes.
Reviewed by the PeptideAtlas Editorial Team.
| Molecular weight | ~5963 g/mol |
|---|---|
| Half-life | ~10 minutes (IV) |
| Production method | recombinant |
| Anti-doping status | not-listed |
| US regulatory status | Not FDA-approved. Development halted after RELAX-AHF-2 failure. |
RELAX-AHF-2, the largest acute heart failure trial with serelaxin (n=6545), failed to show benefit on either co-primary endpoint (worsening heart failure through day 5, or cardiovascular death through day 180). The earlier smaller RELAX-AHF trial had been promising but could not be replicated at scale.
Yes. While Novartis abandoned the acute heart failure program, academic researchers continue investigating relaxin-2 for hepatic fibrosis, portal hypertension, and HFpEF, where its anti-fibrotic properties may be more relevant.
Human Relaxin-2 is a peptide hormone structurally similar to insulin, composed of two chains (A and B) connected by disulfide bonds. It was originally identified for its role in pregnancy (relaxing pelvic ligaments) but has been extensively studied for cardiovascular applications, particularly acute heart failure. Serelaxin (recombinant relaxin-2) showed promising early results for acute heart…
On the PeptideAtlas A–F scale, Human Relaxin-2 is rated C (Early Evidence). Early human evidence, limited trials, or mixed findings
Phase 3 completed (RELAX-AHF-2 failed primary endpoint). Development halted by Novartis. Research continues in fibrosis indications.