Second-generation inhibitors of Bruton tyrosine kinase

  • J Hematol Oncol. 2016 Sep 2;9(1):80. doi: 10.1186/s13045-016-0313-y.
Jingjing Wu  1 ,  Christina Liu  2 ,  Stella T Tsui  3 ,  Delong Liu  4
Affiliations
  • 1. Department of Oncology, The first Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
  • 2. Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL, 60208, USA.
  • 3. SUNY Stony Brook University, Stony Brook, NY, 11794, USA.
  • 4. Department of Oncology, The first Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. [email protected].
PMID: 27590878 DOI: 10.1186/s13045-016-0313-y
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.

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