Erlotinib binds both inactive and active conformations of the EGFR tyrosine kinase domain.
Erlotinib and gefitinib, tyrosine kinase inhibitors used to block EGFR
(epidermal growth factor receptor) signalling in cancer, are thought to bind
only the active conformation of the EGFR-TKD (tyrosine kinase domain). Through
parallel computational and crystallographic studies, we show in the present
study that erlotinib also binds the inactive EGFR-TKD conformation, which may
have significant implications for its use in EGFR-mutated cancers.