Imatinib mesylate (Gleevec) revolutionised CML treatment by specifically targeting:
- A The BCR-ABL fusion tyrosine kinase by occupying the ATP-binding site in its inactive conformation, inhibiting constitutive kinase activity ✓
- B Bcl-2 anti-apoptotic protein, restoring apoptosis in CML blasts
- C The Philadelphia chromosome breakpoint, preventing BCR-ABL mRNA transcription
- D CD20 antigen on CML blast cells, recruiting complement-dependent cytotoxicity
Correct answer: A. The BCR-ABL fusion tyrosine kinase by occupying the ATP-binding site in its inactive conformation, inhibiting constitutive kinase activity
Explanation
Imatinib is a selective small-molecule tyrosine kinase inhibitor that binds to the ATP-binding pocket of the BCR-ABL fusion kinase in its inactive (DFG-out) conformation, preventing substrate phosphorylation and blocking the constitutively active signalling that drives CML blast proliferation. This targeted mechanism spares most normal cells with dramatic efficacy and tolerability. Bcl-2 inhibition is venetoclax. CD20 targeting is rituximab (used in B-cell lymphomas/CLL, not CML). Imatinib does not act at the DNA/RNA level to prevent BCR-ABL transcription.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.