Imatinib mesylate revolutionised CML treatment. Its mechanism of action is:
- A Inhibition of proteasome 26S in CML cells, inducing apoptosis by accumulating pro-apoptotic proteins
- B Monoclonal antibody binding to the extracellular domain of BCR-ABL, targeting CML cells for ADCC
- C Competitive inhibition of the ATP-binding site of BCR-ABL tyrosine kinase, preventing phosphorylation of downstream signalling substrates ✓
- D Alkylation of BCR-ABL DNA at the N7 guanine position, causing CML cell death
Correct answer: C. Competitive inhibition of the ATP-binding site of BCR-ABL tyrosine kinase, preventing phosphorylation of downstream signalling substrates
Explanation
Imatinib is a small molecule tyrosine kinase inhibitor that competitively binds the ATP-binding pocket of the BCR-ABL fusion kinase (produced by the Philadelphia chromosome t(9;22) translocation). By occupying the ATP site, it locks BCR-ABL in an inactive conformation, preventing ATP binding and phosphorylation of downstream proliferative signals (RAS-MAPK, PI3K-AKT, JAK-STAT). This targeted molecular mechanism induces remission in CML with minimal effects on normal cells, representing the first rationally designed targeted cancer therapy.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.