title: Erlotinib binds both inactive and active conformations of the EGFR tyrosine kinase domain.
abstract: 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.
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jin H
authors.initials: JH
authors.lastname: Park
authors.forename: Yingting
authors.initials: Y
authors.lastname: Liu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lemmon
authors.forename: Ravi
authors.initials: R
authors.lastname: Radhakrishnan
mesh_terms: D000818:Animals; D002460:Cell Line; D018360:Crystallography, X-Ray; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D000069347:Erlotinib Hydrochloride; D006801:Humans; D007313:Insecta; D011487:Protein Conformation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000187:drug effects; D011799:Quinazolines / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors