Venetoclax is used in CLL and AML. Its mechanism of action is:

• A Inhibition of MDM2, stabilising p53 to restore apoptosis signalling in CLL cells
• B Inhibition of Bruton's tyrosine kinase (BTK), blocking B-cell receptor signalling pathway
• C Targeting mutant IDH1/IDH2 to reduce 2-hydroxyglutarate production and restore differentiation
• D Selective BCL-2 inhibition, displacing pro-apoptotic proteins (BAX, BAK) to trigger intrinsic apoptosis ✓

Explanation

Venetoclax is a selective, high-potency BCL-2 inhibitor (BH3-mimetic). CLL cells overexpress BCL-2, which sequesters pro-apoptotic proteins BAX and BAK. Venetoclax competitively binds the BH3-binding groove of BCL-2, displacing sequestered BAX/BAK, triggering mitochondrial outer membrane permeabilisation, cytochrome c release and caspase activation. Ibrutinib targets BTK; ivosidenib/enasidenib target IDH1/IDH2; MDM2 inhibitors (e.g., navtemadlin) target p53 stabilisation.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.