Cemadotin

Summary

Cemadotin (LU103793) is a synthetic water-soluble pentapeptide analogue of dolastatin 15, a natural antimitotic peptide. It was investigated as an anticancer agent in Phase I and Phase II clinical trials for various solid tumors and hematologic malignancies. Clinical development was largely halted due to dose-limiting cardiovascular toxicities and modest single-agent efficacy.

Mechanism of Action

Inhibits tubulin polymerization by binding to the vinca alkaloid site on beta-tubulin, preventing microtubule assembly and causing mitotic arrest at G2/M phase, leading to apoptosis in rapidly dividing cancer cells.

Routes of Administration

Goals & Uses

• Solid tumor treatmentOncologyModerate
• Hematologic malignancy treatmentOncologyLow
• Tubulin polymerization inhibitionPharmacological MechanismHigh

Contraindications

• Severe hepatic impairmentOrganHighLiver function concerns
• Cardiovascular disease / conduction disordersCardiacHigh
• Severe bone marrow suppressionHematologicModerate

Adverse Effects

• Peripheral neuropathyNeurologicalUncommon
• HypotensionCardiovascularCommonLow blood pressure
• Nausea and vomitingGastrointestinalCommon
• NeutropeniaHematologicCommonLow neutrophil count
• FatigueGeneralCommonLow energy or tiredness
• BradycardiaCardiovascularCommon

Drug Interactions

• CYP3A4 inhibitorsModerate
• Other cardiotoxic agentsHigh
• Other myelosuppressive agentsModerate

Population Constraints

• Elderly patients with cardiac comorbiditiesAge/CardiacRelative
• Pediatric patientsAgeRelative
• Pregnant or lactating womenReproductiveAbsolute

Regulatory Status

• European UnionInvestigationalEuropean clinical trials conducted (BASF/Knoll); never received EMA marketing authorization.
• United StatesInvestigationalInvestigated under IND but never approved by FDA; clinical development discontinued.

Never received regulatory approval in any jurisdiction. Development discontinued after Phase II trials showed cardiovascular toxicity (hypotension, bradycardia) and limited clinical benefit as a single agent. Served as a structural template for antibody-drug conjugate (ADC) warheads such as monomethyl auristatin E (MMAE).

Evidence & Sources

No sources recorded yet.