ADP-Glo™ Kinase Profiling Systems for Targeted and Flexible Kinase Inhibitor Profiling
Poster Dec 18, 2013
Jacquelyn Hennek, Juliano Alves, Said Goueli, and Hicham ZegzoutiPromega Corporation, 2800 Woods Hollow Road, Madison, WI 53711
Drug safety is of paramount importance in the pharmaceutical industry indicating that minimal side effects constitute a major requirement in drug development. Therefore, novel drug candidates need to be profiled against various liability targets, including a broad panel of kinases to provide a better understanding of off-target activities. Potentially, profiling can also identify new targets that may lead to novel therapeutic indications. A universal, robust and affordable technology is desirable to assess selectivity and potency of drug candidates against multiple classes of kinases. The luminescent ADP-Glo™ kinase assay is a universal platform that measures kinase activity by quantifying the amount of ADP produced during the enzymatic reaction. We have tested the utility of this platform with 174 optimized Kinase Enzyme Systems (KES) spanning different families of the human kinome. Here we present standardized Kinase Profiling Systems for simple kinase inhibitor profiling studies.The Kinase Profiling Systems are a set of kinases organized by families and presented in easy to use multi-well strips. Each strip contains eight enzymes each with their corresponding substrates, and standardized for optimal kinase activity for inhibitor profiling. Using the profiling strips we easily generated selectivity profiles, identifying compound promiscuity towards members of a single kinase subfamily or different subfamilies of the kinome. The ADP-Glo™ KES platforms now address the needs of basic kinase characterization, kinase screening, mode of action (MOA) studies and profiling in an affordable manner using one assay format.