This document is an accompaniment to a published report [Schwartz et al. (2014) Proc. Natl. Acad. Sci. USA 111, 173-178] on covalent inhibition the EGFR kinase. It describes in detail the raw experimental data that were used to generate the list of Ki and kinact values specifically for...
Owing to their covalent target occupancy, irreversible inhibitors require low exposures and offer long duration, and their use thus represents a powerful strategy for achieving pharmacological efficacy. Importantly, the potency metric of irreversible inhibitors is kinact/KI not IC50. A simple approach to...
IC50 values are often employed as descriptors of enzyme inhibition and inhibitor selectivity, but can be misleading in the study of time-dependent, covalent inhibitors. Due to this disconnect, the second-order rate constant, kinact/KI, is a more appropriate metric of covalent-inhibitor potency. ...
Rapid Determination of the Specificity Constant of Irreversible Inhibitors (kinact/KI) by Means of an Endpoint Competition AssayEnzymkinetikIrreversible HemmungKovalente InhibitorenWirkstoffentwicklungOwing to their covalent target occupancy, irreversible inhibitors require low exposures and offer long duration,...