Imatinib mesylate achieves durable molecular remissions in chronic myeloid leukemia through which pharmacological action?
- A Competitive inhibition of the ATP-binding site of the BCR-ABL1 tyrosine kinase domain ✓
- B Covalent alkylation of DNA leading to cross-linking of strands
- C Stabilization of the topoisomerase II-DNA cleavable complex
- D Antagonism of the retinoic acid receptor corepressor complex
Correct answer: A. Competitive inhibition of the ATP-binding site of the BCR-ABL1 tyrosine kinase domain
Explanation
Imatinib mimics the adenine of ATP and occupies the ATP-binding cleft of the constitutively active BCR-ABL1 kinase domain, preventing phosphorylation of downstream substrates that drive proliferation and survival of the leukemic clone. Alkylating agents and topoisomerase II inhibitors are conventional cytotoxics without specificity for BCR-ABL1, and the retinoic acid pathway is the target of all-trans retinoic acid in promyelocytic leukemia.
Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.