Beyond Thermodynamics: Drug Binding Kinetics Could Influence Epidermal Growth Factor Signaling

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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.

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