PM02734

Summary

PM02734 (Irvalec, also known as Elisidepsin) is a synthetic cyclic depsipeptide derived from the marine natural product Kahalalide F, developed by PharmaMar. It has been investigated as an antitumor agent, particularly in solid tumors. It disrupts spliceosomal function and has shown cytotoxic activity against multiple cancer cell lines, including those with EGFR or ErbB3 expression.

Mechanism of Action

Inhibits RNA splicing by targeting the spliceosome, specifically interfering with the SF3b complex and U2 snRNP assembly, leading to cell cycle arrest and apoptosis in tumor cells.

Routes of Administration

Goals & Uses

• RNA splicing inhibitionMolecular TargetModerate
• Antitumor activity in solid tumorsOncologyModerate
• Targeting EGFR/ErbB3-expressing tumorsOncologyModerate

Contraindications

• Severe hepatic impairmentOrganHighLiver function concerns
• Known hypersensitivity to elisidepsin or excipientsAllergy/hypersensitivityHigh

Adverse Effects

• Peripheral neuropathyNeurologicalUncommon
• HepatotoxicityHepaticUncommonLiver injury or dysfunction
• Nausea and vomitingGastrointestinalCommon
• FatigueGeneralCommonLow energy or tiredness
• MyelosuppressionHematologicUncommon

Drug Interactions

• CYP3A4 inhibitorsModerate
• Other spliceosome inhibitorsHigh

Population Constraints

• PregnancyReproductive SafetyAbsolute
• Pediatric patientsAgeRelative
• Patients with severe renal impairmentOrgan ImpairmentRelative

Regulatory Status

• European UnionInvestigationalDeveloped by PharmaMar (Spain); no EMA marketing authorization granted.
• United StatesInvestigationalStudied in Phase I/II trials; no FDA approval obtained.
• United KingdomUnknownNo known separate MHRA approval; followed EU investigational status.

PM02734 has been studied in Phase I and Phase II clinical trials for solid tumors, including non-small cell lung cancer and head and neck cancers, but has not received regulatory approval in any major jurisdiction.

Evidence & Sources

No sources recorded yet.