scanKINETIC: A broadly applicable tool for the kinetic characterization of interactions between small molecule inhibitors and protein targets from the kinase and bromodomain families

scanKINETIC: A broadly applicable tool for the kinetic characterization of interactions between small molecule inhibitors and
protein targets from the kinase and bromodomain families
Version:
V1

File Name/Number:
2013 SLAS

Year:
2013

Inhibitor association and dissociation kinetics can have important effects on a compound’s drug-like properties and in vitro, cellular, and in vivo behaviors. The association and dissociation rates for protein target-inhibitor complexes are variable and can be both inhibitor and protein-dependent. In addition, it is often important to classify inhibitors as being reversible or irreversible (covalent). While many inhibitor complexes form and dissociate rapidly (< minutes), others can have extraordinarily low association and/or dissociation rates, requiring several hours to reach equilibrium. Slowly associating and/or dissociating inhibitors can yield conflicting potency data in various in vitro, cellular, and in vivo settings, where the inhibitor-target equilibration time is often assay specific. Though there are several methods available for measuring inhibitor binding kinetics, most available offerings currently address only a small subset of relevant protein targets. Here we describe scanKINETIC, a  semi-quantitative, broadly applicable tool based on proven KINOMEscan & BROMOscan technologies, which enables the kinetic characterization of inhibitor interactions. scanKINETIC is currently applicable to an industry-leading fraction of the 518 known protein kinases and for a rich sampling of lipid, atypical, and clinically relevant mutant kinases. In addition, scanKINETIC can be applied bromodomain epigenetic reader proteins. Relevant exemplary data for known inhibitors are presented and discussed.