Imatinib mesylate achieves remission in CML by specifically targeting BCR-ABL tyrosine kinase. The mechanism by which it inhibits this kinase is:

• A Irreversible covalent binding to the ATP-binding site, permanently inactivating the kinase
• B Allosteric binding to the SH2 domain, preventing substrate docking
• C Promoting ubiquitin-mediated proteasomal degradation of BCR-ABL protein
• D Competitive binding to the ATP-binding pocket, stabilizing BCR-ABL in its inactive conformation ✓

Explanation

Imatinib is a type II tyrosine kinase inhibitor that competitively occupies the ATP-binding pocket of BCR-ABL, but specifically when the kinase is in its inactive (DFG-out) conformation. This conformational selectivity distinguishes it from type I inhibitors (which bind the active DFG-in conformation). By stabilizing the inactive conformation, imatinib blocks ATP binding and prevents phosphorylation of downstream substrates driving proliferation. The T315I gatekeeper mutation (in the ATP pocket contact residue) confers resistance to imatinib and most second-generation TKIs.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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