Dolastatin 10

Summary

Dolastatin 10 is a potent antimitotic pentapeptide originally isolated from the sea hare Dolabella auricularia. It demonstrates nanomolar cytotoxicity against a wide range of cancer cell lines by inhibiting tubulin polymerization. Although it showed insufficient efficacy as a standalone agent in clinical trials, it served as the pharmacophore for the development of monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF), which are widely used as payloads in antibody-drug conjugates (ADCs) such as brentuximab vedotin.

Mechanism of Action

Binds to tubulin at the vinca domain, inhibiting tubulin polymerization and microtubule assembly, leading to mitotic arrest and apoptosis in rapidly dividing cells

Routes of Administration

Goals & Uses

• Anticancer activityOncologyModerate
• Tubulin inhibition researchBasic ResearchHigh
• ADC payload scaffoldDrug DevelopmentHigh

Contraindications

• Severe hepatic impairmentOrganModerateLiver function concerns
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Severe bone marrow suppressionHematologicHigh

Adverse Effects

• Peripheral neuropathyNeurologicalUncommon
• Myelosuppression / neutropeniaHematologicCommon
• AlopeciaDermatologicUncommonHair loss
• ConstipationGastrointestinalUncommonReduced bowel frequency or difficulty passing stool
• Nausea and vomitingGastrointestinalCommon
• FatigueGeneralCommonLow energy or tiredness

Drug Interactions

• Vinca alkaloidsModerate
• CYP3A4 inhibitors (e.g., ketoconazole)Moderate
• Other myelosuppressive agentsHigh

Population Constraints

• Pediatric patientsAgeRelative
• Severely immunocompromised patientsImmunologicalRelative
• Pregnant womenReproductiveAbsolute
• Patients with pre-existing neuropathyNeurologicRelative

Regulatory Status

• European UnionUnapprovedNo EMA marketing authorization; strictly research/investigational use
• United StatesUnapprovedInvestigated in NCI-sponsored Phase II trials; never received FDA approval as a standalone agent
• United KingdomUnapprovedNo MHRA approval; research compound only

Dolastatin 10 itself has not received regulatory approval in any jurisdiction. Clinical trials in the 1990s–2000s showed limited single-agent efficacy. Its synthetic analogs (auristatins) have been approved as ADC payloads.

Evidence & Sources

No sources recorded yet.