Birinapant

Summary

Birinapant (TL32711) is a bivalent Smac mimetic peptidomimetic developed by TetraLogic Pharmaceuticals for the treatment of various cancers. It induces apoptosis by antagonizing IAP proteins, particularly cIAP1, cIAP2, and XIAP. It has been evaluated in clinical trials for hematologic malignancies (including MDS and AML) and solid tumors, both as monotherapy and in combination with chemotherapy or other anticancer agents.

Mechanism of Action

Birinapant is a bivalent Smac mimetic that binds to and antagonizes inhibitor of apoptosis proteins (IAPs), particularly cIAP1, cIAP2, and XIAP. It promotes autoubiquitination and proteasomal degradation of cIAP1/2, activates both intrinsic and extrinsic apoptotic pathways, and sensitizes cancer cells to TNF-alpha-induced cell death via activation of caspases.

Routes of Administration

Goals & Uses

• Solid tumor treatmentOncologyLow
• Sensitization to chemotherapyCombination Oncology TherapyModerate
• Apoptosis induction in cancer cellsOncologyModerate
• Treatment of myelodysplastic syndromes (MDS)OncologyModerate
• Treatment of acute myeloid leukemia (AML)Hematologic MalignancyModerate

Contraindications

• Severe hepatic impairmentOrganModerateLiver function concerns
• Active uncontrolled infectionInfectious DiseaseModerate
• Known hypersensitivity to birinapant or its componentsAllergyHigh

Adverse Effects

• ThrombocytopeniaHematologicUncommonLow platelet count
• Facial palsy (Bell's palsy / cranial nerve VII palsy)NeurologicalUncommon
• Nausea and vomitingGastrointestinalCommon
• FatigueGeneralCommonLow energy or tiredness
• Increased liver enzymes (transaminitis)HepaticUncommon
• Infusion-related reactionsHypersensitivityUncommon

Drug Interactions

• TNF-alpha-inducing agentsModerate
• CYP3A4 inhibitors/inducersLow
• 5-Azacitidine (Azacitidine)Low

Population Constraints

• Severe renal impairmentOrgan ImpairmentRelative
• Pediatric patientsAgeRelative
• Pregnant womenReproductiveRelative
• Patients with pre-existing cranial nerve disordersNeurologicalRelative

Regulatory Status

• European UnionInvestigationalNo EMA approval; investigated under clinical trial authorizations in European centers.
• United StatesInvestigationalFDA Orphan Drug Designation granted for MDS. Multiple Phase I/II trials completed or ongoing. Not FDA-approved for any indication.
• United KingdomInvestigationalNot approved by MHRA; available only within clinical trial settings.

Birinapant has not received FDA, EMA, or MHRA approval. It has been investigated in multiple Phase I and Phase II clinical trials. Orphan Drug Designation was granted by the FDA for myelodysplastic syndromes (MDS). Development was conducted by TetraLogic Pharmaceuticals; subsequent rights were acquired by Medivir.

Evidence & Sources

No sources recorded yet.