Human Relaxin-2

Human Relaxin-2 Overview

Human Relaxin-2, marketed in recombinant form as serelaxin, is a peptide hormone that acts mainly through the RXFP1 receptor to produce systemic and renal vasodilation via nitric oxide and bradykinin pathways. It has been studied primarily for its ability to reduce vascular resistance, improve perfusion to organs, and exert anti-fibrotic and anti-inflammatory effects in cardiovascular and liver conditions. As a peptide, it is handled as a research chemical with purity and storage caveats.

Editorial Verdict

This is one of the better-studied compounds in the peptide space, with a substantial body of human trial data behind it. That said, the clinical story is cautionary rather than triumphant: despite encouraging early results, serelaxin stumbled in late-stage trials and never became a widely available product. It is effective for short-term effects but unproven for the long-term outcomes that matter most.

Evidence Quality

We assign a research grade of A+. The grade rests on 198 peer-reviewed studies, comprising 14 RCTs, 5 meta-analyses, 24 observational studies, 73 animal studies, 39 in vitro studies, and 43 reviews. Of 198 classified findings, 125 were supportive, 50 mixed, 15 null, and 8 refuting. The human base is solid at 14 RCTs and 5 meta-analyses, making this far better evidenced than most peptides.

What the Research Shows

The Phase III RELAX-AHF trial reported that serelaxin meaningfully improved shortness of breath and reduced 180-day mortality in acute heart failure patients. A review explored its promise for heart failure with preserved ejection fraction through anti-inflammatory, anti-fibrotic, and anti-oxidative signaling. Animal work showed that a single injection can produce sustained, bradykinin-driven vascular relaxation that persists even after the peptide clears the blood, and another animal study found it reshapes lipid metabolism and lowers inflammation in fat tissue. A Phase 2 trial (STOPP) suggested it may ease portal hypertension and provide anti-fibrotic benefit in liver cirrhosis. The overall picture is strong for short-term hemodynamics but inconsistent for large-population, long-term endpoints.

Dosage

Standard clinical research uses 30 μg/kg/day as a continuous IV infusion over 48 hours. Experimental rat models have used single 13.3 μg/kg injections to observe lasting vascular effects. Because the native peptide has a very short half-life, researchers have developed lipidated analogs to extend its action.

Who Should Be Cautious

Its potent vasodilation can cause excessive drops in blood pressure. IV delivery brings the usual infusion-site reactions, and although uncommon, heart-rate changes are monitored given its cardiovascular impact. Symptom relief and results tend to be better in patients with preserved kidney function.

Availability

Serelaxin was developed by Novartis but ran into regulatory setbacks after its Phase 3 failures and is not widely available as a commercial product. It is mainly accessible through chemical supply houses for laboratory research and is not meant for over-the-counter use.

Bottom Line

Well-evidenced and genuinely useful for acute, short-term stabilization, but its failure to clear late-stage trials means the long-term benefits remain unproven and it is not a finished therapy.