Zoptarelin doxorubicin

Peptide Drug Conjugate (LHRH Agonist Cytotoxic Conjugate)Rx: InvestigationalCompound: Investigational

Also known as: AEZS-108, AN-152, D-Lys6-LHRH-doxorubicin, Zoptrex

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

Summary

Zoptarelin doxorubicin (AEZS-108) is an investigational peptide-drug conjugate designed for targeted delivery of doxorubicin to LHRH receptor-expressing tumors, including endometrial, ovarian, and prostate cancers. It combines the tumor-targeting specificity of an LHRH agonist with the cytotoxic activity of doxorubicin to reduce systemic toxicity compared to free doxorubicin. Phase II and III clinical trials have been conducted, but the compound did not achieve its primary endpoint in the pivotal Phase III LHRH-targeted endometrial cancer trial.

Mechanism of Action

Zoptarelin doxorubicin (AEZS-108) is a targeted cytotoxic conjugate in which a luteinizing hormone-releasing hormone (LHRH) agonist peptide (D-Lys6-LHRH) is covalently linked to doxorubicin. The LHRH peptide moiety binds to LHRH receptors overexpressed on certain tumor cells, facilitating receptor-mediated endocytosis and intracellular delivery of doxorubicin, which then intercalates into DNA and inhibits topoisomerase II, leading to apoptosis.

Routes of Administration

Intravenous

Goals & Uses

  • Reduction of systemic doxorubicin toxicity via tumor targetingToxicity ReductionModerate
  • Targeted treatment of ovarian cancerOncologyLow
  • Targeted treatment of LHRH receptor-positive endometrial cancerOncologyModerate
  • Targeted treatment of castration-resistant prostate cancerOncologyLow

Contraindications

  • Severe pre-existing cardiomyopathy or heart failureCardiovascularHigh
  • Severe hepatic impairmentOrganModerateLiver function concerns
  • Hypersensitivity to doxorubicin or LHRH analoguesAllergyHigh
  • Cumulative anthracycline dose at or near maximum lifetime limitOncologyHigh

Adverse Effects

  • CardiotoxicityCardiovascularUncommon
  • AlopeciaDermatologicCommonHair loss
  • Hot flashes / hormonal effectsEndocrineUncommon
  • Fatigue and astheniaConstitutionalCommon
  • Nausea and vomitingGastrointestinalCommon
  • Myelosuppression (neutropenia, anemia, thrombocytopenia)HematologicalCommon

Drug Interactions

  • Live vaccinesHigh
  • Other anthracyclines or cardiotoxic agentsHigh
  • CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin)Moderate

Population Constraints

  • PregnancyReproductive SafetyAbsolute
  • Pediatric patientsAgeRelative
  • Patients with LHRH receptor-negative tumorsBiomarkerRelative
  • BreastfeedingReproductiveAbsolute

Regulatory Status

  • European UnionInvestigationalInvestigated under clinical trials; no EMA marketing authorization granted.
  • United StatesInvestigationalFDA granted orphan drug designation for endometrial cancer. No approval granted. Phase III trial (ZoptEC) did not meet primary endpoint.

The FDA granted orphan drug designation for zoptarelin doxorubicin in endometrial cancer. However, a Phase III trial (ZoptEC) did not meet its primary endpoint of overall survival improvement versus doxorubicin in endometrial cancer. No regulatory approval has been granted in the US or EU.

Evidence & Sources

No sources recorded yet.

Browse All PeptidesBuild My Stack