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
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
Overlay of SPR binding curves for ibrutinib on BTK and EGFR
NTRC Oncolines Volcano Ibrutinib Hotspots RL95 2
ANOVA analysis relating effects of ibrutinib on cell panel proliferation to hotspot cancer gene mutations and copy-number variations