Second-generation inhibitors of Bruton tyrosine kinase

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

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.

Figures

Fig. 1
Fig. 1
The structure of Bruton tyrosine kinase (BTK). BTK has a pleckstrin-homology (PH) domain, SH3 and SH2 (src-homology) domains, and a kinase domain. The BTK polypeptide has 659 amino acid residues with an approximate molecular weight of 76 kDa. The C481S mutation in the kinase domain mediates resistance to ibrutinib

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Source: PubMed

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