Imatinib (a BCR-ABL tyrosine kinase inhibitor) is used for CML. The T315I gating mutation of BCR-ABL confers resistance to imatinib, dasatinib, and nilotinib. Which drug overcomes T315I resistance?
- A Bosutinib
- B Ponatinib ✓
- C Rebastinib
- D Venetoclax
Correct answer: B. Ponatinib
Explanation
The T315I mutation ('gatekeeper mutation') replaces a threonine residue that forms a critical hydrogen bond with first- and second-generation TKIs (imatinib, dasatinib, nilotinib, bosutinib), eliminating drug binding. Ponatinib is a third-generation, pan-BCR-ABL TKI designed with a carbon-carbon triple bond that bypasses the steric hindrance introduced by T315I, retaining potent inhibitory activity. Venetoclax is a BCL-2 inhibitor used in AML/CLL and does not target BCR-ABL.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.