Mechanism of action

Bosutinib is a tyrosine kinase inhibitor of the BCR-ABL kinase that promotes CML; it is also an inhibitor of SRC-family kinases including SRC, LYN, and HCK1

BOSULIF is a potent inhibitor against the majority of imatinib-resistant BCR-ABL mutations2,3

  • Evaluated in vitro, bosutinib inhibited 16 of 18 imatinib-resistant forms of BCR-ABL expressed in murine myeloid cell lines, with the exceptions of V299L and T315I1,2,4

Preclinical inhibition does not necessarily correlate with clinical activity.


References
  1. BOSULIF Prescribing Information. New York, NY: Pfizer Inc.
  2. Redaelli S, Piazza R, Rostagno R, et al. Activity of bosutinib, dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants. J Clin Oncol. 2009;27(3):469-471.
  3. Hantschel O, Grebien F, Superti-Furga G. The growing arsenal of ATP-competitive and allosteric inhibitors of BCR-ABL. Cancer Res. 2012;72(19):4890-4895.
  4. Apperley JF. Part I: mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol. 2007;8(11):1018-1029.
  5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myeloid Leukemia V.1.2018. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed August 8, 2017. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content or its use or application and disclaims any responsibility for its use or application in any way.