Valspodar

Cyclic Peptide (cyclosporin D Analogue)Rx: ResearchCompound: Withdrawn

Also known as: Cyclosporin D analogue MDR inhibitor, PSC 833, PSC-833, SDZ PSC 833

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

Summary

Valspodar (PSC 833) is a non-immunosuppressive cyclosporin D analogue developed as a first-generation P-glycoprotein inhibitor to overcome multidrug resistance in cancer. Despite promising preclinical and early clinical results, Phase III trials failed to demonstrate improved overall survival and showed increased toxicity due to pharmacokinetic interactions with co-administered chemotherapy. Development was discontinued.

Mechanism of Action

Potent inhibitor of P-glycoprotein (P-gp, ABCB1), a multidrug efflux transporter. Binds to P-gp and blocks its ability to pump chemotherapeutic agents out of cancer cells, thereby reversing multidrug resistance (MDR) and increasing intracellular drug accumulation.

Routes of Administration

IntravenousOral

Goals & Uses

  • Reversal of multidrug resistance in cancerOncology / Pharmacology ResearchModerate
  • Improved chemotherapy efficacy in solid tumorsOncology / Solid TumorsLow
  • Improved chemotherapy efficacy in AMLOncology / Hematologic MalignancyLow

Contraindications

  • Severe hepatic impairmentOrganHighLiver function concerns
  • Concurrent use with drugs highly dependent on CYP3A4/P-gp for clearanceDrug InteractionHigh

Adverse Effects

  • Hypersensitivity reactionsImmunologicRare
  • NeurotoxicityNeurologicalUncommon
  • Enhanced chemotherapy toxicity (myelosuppression, neuropathy)Pharmacokinetic Interaction Mediated ToxicityCommon
  • Nausea and vomitingGastrointestinalCommon
  • Hyperbilirubinemia / hepatotoxicityHepaticUncommon

Drug Interactions

  • DoxorubicinHigh
  • PaclitaxelHigh
  • Cyclosporin AModerate
  • EtoposideModerate
  • VincristineHigh

Population Constraints

  • Patients with significant hepatic dysfunctionOrgan ImpairmentRelative
  • Pediatric patientsAgeRelative
  • Pregnant womenReproductiveAbsolute

Regulatory Status

  • European UnionUnapprovedInvestigated in European clinical trials (e.g., HOVON); never received EMA approval.
  • United StatesUnapprovedInvestigated under IND; never received FDA approval. Development discontinued after failed Phase III trials.
  • United KingdomUnapprovedNo regulatory approval; research use only.

Never received regulatory approval in any major jurisdiction. Development halted following negative Phase III clinical trial results in the late 1990s and early 2000s. Considered a withdrawn/discontinued investigational compound.

Evidence & Sources

No sources recorded yet.

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