Journal of Hematology & Oncology (Sep 2016)

Second-generation inhibitors of Bruton tyrosine kinase

  • Jingjing Wu,
  • Christina Liu,
  • Stella T. Tsui,
  • Delong Liu

DOI
https://doi.org/10.1186/s13045-016-0313-y
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 7

Abstract

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Abstract Bruton tyrosine kinase (BTK) is a critical effector molecule for B cell development and plays a major role in lymphoma genesis. Ibrutinib is the first-generation BTK inhibitor. Ibrutinib has off-target effects on EGFR, ITK, and Tec family kinases, which explains the untoward effects of ibrutinib. Resistance to ibrutinib was also reported. The C481S mutation in the BTK kinase domain was reported to be a major mechanism of resistance to ibrutinib. This review summarizes the clinical development of novel BTK inhibitors, ACP-196 (acalabrutinib), ONO/GS-4059, and BGB-3111.