BTK inhibitor ibrutinib is also effective on other kinases

Biochemical and cellular assays support clinical evaluation of ibrutinib

  • The BTK inhibitor ibrutinib is FDA-approved for mantle cell lymphoma and several leukemias.

  • The compound inhibits kinases with a reactive cysteine at the same position as in BTK (Cys481), such as EGFR, HER2, and HER4 (the protein products of the EGFR, ERBB2, and ERBB4 genes).

  • The binding of ibrutinib to BTK and EGFR was additionally confirmed by SPR.

  • Proliferation assays and analyses of mutations and copy-number variations revealed that amplification of ERBB2 relates to sensitivity for ibrutinib.

  • Moreover, gene expression analysis revealed that ERBB2 is one of the most significant sensitivity markers, together with ERBB4.

  • The biochemical and cell panel profiling experiments support the clinical evaluation of ibrutinib in HER2-driven cancers (NCT02884453) and ERBB4-overexpressing cancers (Rauf et al., 2018).

Kinase Inhibition (%)
BTK 100
EGFR 89
HER2 100
HER4 99
Inhibition (%) of selected kinases by ibrutinib at a single concentration of 1 µM in individual kinase assays.
Overlay of SPR binding curves for ibrutinib on BTK and EGFR.
ANOVA analysis relating effects of ibrutinib on cell panel proliferation to hotspot cancer gene mutations and copy-number variations.