title: Beyond thermodynamics: drug binding kinetics could influence epidermal growth factor signaling.
abstract: We modeled the kinetics of drug binding to protein kinases in the EGF signaling pathway relevant to non-small-cell lung cancer and found that binding kinetics could influence therapeutic potential, that fast binding kinetics was advantageous for most targets with a couple of exceptions, that targeting some protein kinases could enhance rather than attenuate the pathway, and that IC(50) could be sensitive to the kinetic parameters of drug binding.
authors.affiliation: Department of Chemistry and Biochemistry and the Center for Nanoscience, University of Missouri-Saint Louis, One University Boulevard, St. Louis, Missouri 63121, USA.
authors.forename: Mayank
authors.initials: M
authors.lastname: Goyal
authors.forename: Michael
authors.initials: M
authors.lastname: Rizzo
authors.forename: Frank
authors.initials: F
authors.lastname: Schumacher
authors.forename: Chung F
authors.initials: CF
authors.lastname: Wong
mesh_terms: D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D000069437:Pharmacological Phenomena; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects*; D013816:Thermodynamics
chemical_list: D004364:Pharmaceutical Preparations; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases
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