Taltobulin

Summary

Taltobulin (HTI-286) is a synthetic tripeptide analog of hemiasterlin developed by Wyeth (now Pfizer) as an anticancer agent. It inhibits tubulin polymerization through a mechanism distinct from taxanes and vinca alkaloids, and shows activity in multidrug-resistant tumors. It was evaluated in Phase I/II clinical trials for solid tumors including non-small cell lung cancer and prostate cancer, but development was discontinued due to toxicity and limited efficacy in later-stage trials.

Mechanism of Action

Taltobulin (HTI-286) is a synthetic analog of hemiasterlin, a tripeptide natural product. It binds to the vinca alkaloid domain of tubulin, inhibiting tubulin polymerization, disrupting microtubule dynamics, and causing mitotic arrest at the G2/M phase, ultimately inducing apoptosis in tumor cells. Notably, it retains activity against P-glycoprotein-overexpressing multidrug-resistant cell lines.

Routes of Administration

Goals & Uses

• Prostate cancer treatmentOncologyLow
• Non-small cell lung cancer treatmentOncologyLow
• Antitumor activity in solid tumorsOncologyModerate
• Overcoming multidrug resistanceOncologyModerate

Contraindications

• Severe hepatic impairmentOrganModerateLiver function concerns
• Active uncontrolled infectionInfectious DiseaseModerate
• Pre-existing severe peripheral neuropathyNeurologicalHigh

Adverse Effects

• Peripheral neuropathyNeurologicalCommon
• AlopeciaDermatologicCommonHair loss
• Nausea/vomitingGastrointestinalCommon
• NeutropeniaHematologicUncommonLow neutrophil count
• FatigueGeneralCommonLow energy or tiredness
• Elevated liver enzymesHepaticUncommonIncrease in AST/ALT or other hepatic markers

Drug Interactions

• Other neurotoxic agents (e.g., platinum compounds, vinca alkaloids)Moderate
• CYP3A4 inhibitors (e.g., ketoconazole, itraconazole)Moderate

Population Constraints

• Pediatric patientsAgeRelative
• Pregnant womenReproductiveAbsolute
• Patients with severe renal impairmentOrgan ImpairmentRelative

Regulatory Status

• European UnionInvestigationalNo EMA approval or marketing authorization; investigational use only.
• United StatesInvestigationalEvaluated under IND in Phase I/II trials; development discontinued; no approved indication.
• United KingdomInvestigationalNo MHRA approval; not marketed in the UK.

Taltobulin has not received FDA, EMA, or MHRA approval for any indication. Clinical development was halted after Phase I/II trials; no active IND or regulatory pathway is currently known.

Evidence & Sources

No sources recorded yet.