title: Tyrosine kinase inhibitors - small molecular weight compounds inhibiting EGFR.
abstract: Abnormally elevated EGFR kinase activity can lead to various pathological states, including proliferative diseases such as cancer. The development of selective protein kinase inhibitors has become an important area of drug discovery for the potential treatment of a variety of solid tumors such as breast, ovarian and colorectal cancers, NSCLC, and carcinoma of the head and neck. There are three small molecule EGFR kinase inhibitor drugs in clinical use (gefitinib, erlotinib and lapatinib), and several others are currently undergoing clinical development. This review summarizes the development of EGFR kinase inhibitors, and includes descriptions of the binding modes, the importance of a multiple-targets strategy, the effects of sensitizing and resistance mutations in the EGFR, and molecular diagnostic approaches. In addition, the use of target fishing for selectivity profiling, off-target identification and quantitative structure-activity relationship modeling for the prediction of EGFR inhibition is discussed.
authors.affiliation: Vichem Chemie Research Ltd, Budapest, Hungary.
authors.forename: Bálint
authors.initials: B
authors.lastname: Hegymegi-Barakonyi
authors.forename: Dániel
authors.initials: D
authors.lastname: Eros
authors.forename: Csaba
authors.initials: C
authors.lastname: Szántai-Kis
authors.forename: Nóra
authors.initials: N
authors.lastname: Breza
authors.forename: Péter
authors.initials: P
authors.lastname: Bánhegyi
authors.forename: Gábor Viktor
authors.initials: GV
authors.lastname: Szabó
authors.forename: Edit
authors.initials: E
authors.lastname: Várkondi
authors.forename: István
authors.initials: I
authors.lastname: Peták
authors.forename: László
authors.initials: L
authors.lastname: Orfi
authors.forename: György
authors.initials: G
authors.lastname: Kéri
mesh_terms: D000818:Animals; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008970:Molecular Weight; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries; D066246:ErbB Receptors