TRV-120027

Biased Angiotensin II Receptor Agonist (beta Arrestin Biased AT1R Ligand)Rx: ResearchCompound: Investigational

Also known as: TRV-027, TRV027, TRV120027

Educational Only — Not medical advice. Consult a qualified clinician before using any peptide.

Summary

TRV120027 is a synthetic heptapeptide biased ligand at the AT1 receptor developed by Trevena Inc. It was investigated primarily for acute heart failure (AHF), aiming to reduce cardiac preload/afterload and improve renal perfusion without the rebound hemodynamic deterioration seen with other AHF agents. Despite promising phase II data (BLAST-AHF), it did not demonstrate superiority in the phase II/III program and development was discontinued.

Mechanism of Action

Selectively activates beta-arrestin signaling pathways at the angiotensin II type 1 receptor (AT1R) while blocking Gq-protein-mediated vasoconstriction. This biased agonism promotes cardioprotective signaling (cardiomyocyte survival, reduced apoptosis) and natriuresis without the deleterious hemodynamic effects of conventional AT1R activation.

Routes of Administration

Intravenous

Goals & Uses

  • Cardiomyocyte cytoprotectionCardioprotectionLow
  • Reduction of dyspnea in acute heart failureCardiovascular / HemodynamicModerate
  • Reduction of cardiac preload and afterloadCardiovascular / HemodynamicModerate
  • Renal protection during AHF treatmentRenal / Organ ProtectionLow

Contraindications

  • PregnancyPopulationHighPotential fetal risk or insufficient safety data
  • Hypotension (severe)HemodynamicHigh
  • Severe bilateral renal artery stenosisRenalHigh

Adverse Effects

  • HeadacheNeurologicUncommonPain in the head or upper neck
  • HypotensionCardiovascularCommonLow blood pressure
  • NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
  • Worsening renal functionRenalUncommon

Drug Interactions

  • Antihypertensive agentsModerate
  • ACE inhibitorsHigh
  • Potassium-sparing diureticsModerate

Population Constraints

  • Pediatric populationAgeRelative
  • Pregnant womenReproductiveAbsolute
  • Severe hepatic impairmentOrgan ImpairmentRelative

Regulatory Status

  • European UnionUnapprovedNo regulatory submission or approval in the European Union.
  • United StatesInvestigationalInvestigated under IND; development discontinued after phase II trials did not demonstrate sufficient efficacy. Never approved by FDA.
  • United KingdomUnapprovedNo regulatory submission or approval in the United Kingdom.

Never received regulatory approval in any jurisdiction. Investigated under IND in the United States. Development halted after inconclusive/negative clinical trial results circa 2016-2017.

Evidence & Sources

No sources recorded yet.

Browse All PeptidesBuild My Stack