Project Description
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 |