PL-3994

Natriuretic Peptide Receptor Agonist (cyclic Peptide Mimetic)Rx: ResearchCompound: Investigational

Also known as: Cys(Et)-c[Lys-Asp-Arg-Ile-c(Cys-Phe-Gly)], PL3994

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

Summary

PL-3994 is a synthetic cyclic peptide mimetic of atrial natriuretic peptide (ANP) designed to selectively activate natriuretic peptide receptor-A (NPR-A). It has been investigated for the treatment of acute decompensated heart failure, hypertension, and asthma/bronchoconstriction. Its macrocyclic structure confers resistance to neprilysin (neutral endopeptidase) degradation, potentially offering improved pharmacokinetic stability compared to native natriuretic peptides.

Mechanism of Action

Selective agonist of natriuretic peptide receptor-A (NPR-A/GC-A); binds and activates NPR-A to stimulate cGMP production, leading to vasodilation, natriuresis, diuresis, and suppression of the renin-angiotensin-aldosterone system (RAAS)

Routes of Administration

IntravenousSubcutaneous

Goals & Uses

  • Bronchodilation / asthmaPulmonaryLow
  • Acute decompensated heart failure treatmentCardiovascularModerate
  • Blood pressure reduction / hypertensionCardiovascularModerate
  • Diuresis / natriuresisRenalModerate

Contraindications

  • Severe renal impairmentOrganModerateKidney function concerns
  • Known hypersensitivity to PL-3994 or componentsImmunologicHigh
  • Hypotension or cardiogenic shockCardiovascularHigh

Adverse Effects

  • Injection site reactionsLocalUncommon
  • HeadacheNeurologicUncommonPain in the head or upper neck
  • HypotensionCardiovascularCommonLow blood pressure
  • FlushingVascularUncommonWarmth and redness of the skin

Drug Interactions

  • Antihypertensive agentsModerate
  • DiureticsModerateMay worsen dehydration or electrolyte imbalance
  • Phosphodiesterase-5 inhibitors (e.g., sildenafil)High

Population Constraints

  • PregnancyReproductive SafetyRelative
  • Pediatric patientsAgeRelative
  • Elderly patientsAgeRelative

Regulatory Status

  • European UnionUnknownNo known EMA approval or active marketing authorization application on record
  • United StatesInvestigationalInvestigated under IND by Palatin Technologies; Phase I/II trials completed for heart failure and asthma; no NDA filed
  • United KingdomUnknownNo MHRA approval or active application on record

No approved indication in any major jurisdiction. Investigated in Phase I/II clinical trials. Developed by Palatin Technologies.

Evidence & Sources

No sources recorded yet.

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