Imatinib mesylate revolutionized treatment of CML. Its mechanism of action is best described as:

• A Monoclonal antibody binding to the BCR-ABL protein causing antibody-dependent cytotoxicity
• B Inhibition of topoisomerase II causing DNA double-strand breaks
• C Selective tyrosine kinase inhibitor that competes with ATP for the kinase domain of BCR-ABL, preventing downstream signaling ✓
• D Alkylating the BCR-ABL kinase domain at cysteine residues

Explanation

Imatinib is a small molecule tyrosine kinase inhibitor (TKI) that binds the ATP-binding site of the BCR-ABL fusion protein in its inactive conformation, blocking phosphorylation of downstream substrates that drive uncontrolled CML cell proliferation. It also inhibits c-KIT (important in GIST) and PDGFR. Resistance most commonly develops via T315I mutation in the kinase domain. Nilotinib, dasatinib, and ponatinib are second/third-generation TKIs overcoming most resistance mutations except T315I (ponatinib covers T315I).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.