Structural mechanism of the Pan-BCR-ABL inhibitor ponatinib (AP24534): lessons for overcoming kinase inhibitor resistance.

@article{Zhou2011StructuralMO,
  title={Structural mechanism of the Pan-BCR-ABL inhibitor ponatinib (AP24534): lessons for overcoming kinase inhibitor resistance.},
  author={Tianjun Zhou and Lois Commodore and Wei-Sheng Huang and Yihan Wang and Mathew Thomas and Jeff Keats and Qihong Xu and V. Rivera and William Shakespeare and Tim Clackson and David C Dalgarno and Xiaotian Zhu},
  journal={Chemical biology & drug design},
  year={2011},
  volume={77 1},
  pages={1-11}
}
The BCR-ABL inhibitor imatinib has revolutionized the treatment of chronic myeloid leukemia. However, drug resistance caused by kinase domain mutations has necessitated the development of new mutation-resistant inhibitors, most recently against the T315I gatekeeper residue mutation. Ponatinib (AP24534) inhibits both native and mutant BCR-ABL, including T315I, acting as a pan-BCR-ABL inhibitor. Here, we undertook a combined crystallographic and structure-activity relationship analysis on… CONTINUE READING
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