Product News: EMD Millipore Deposits More Than 70,000 Data Points on Kinase Bioactivity into ChEMBL Database

02 Apr 2013

EMD Millipore's Discovery and Development Solutions business, part of the Life Science division of Merck KGaA of Darmstadt, Germany, today announced that they have deposited kinase bioactivity data in the ChEMBL database consisting of more than 70,000 data points, covering 234 human wildtype kinases and kinase complexes, as well as 158 well-studied kinase inhibitors. These data were the result of a recent study that used broad activity screening to capture selectivity and potency across the kinome. The data will be available in the next version of the ChEMBL database due for release in early May (Chembl_16).

This study was published in Biochemical Journal, Volume 451 on March 28, 2013 (online) and April 15, 2013 (print) under the title A broad activity screen in support of a chemogenomic map for kinase signaling research and drug discovery.

"Despite the development of a number of efficacious kinase inhibitors, the strategies for rational design of these compounds have been limited by target promiscuity," notes Kevin Harvey, Senior Manager for Research and Development at EMD Millipore and lead author of the kinase study. "Through our broad activity profiling strategy, we not only identified potential new uses for known small molecules, but we also established a framework for relating chemical structural similarities to kinome activity and highlighted potential opportunities for probing new targets."

Kinase inhibitors were screened for inhibitory activity against active human kinases and kinase complexes representing all branches of the kinome tree, using the KinaseProfiler™ service. The study employed small molecules identified in the literature as potent and specific inhibitors of kinases important as therapeutic targets and/or signal transduction regulators. Hierarchical clustering of these benchmark kinase inhibitors based upon their kinome activity profiles illustrated how activity profiles related to chemical structure similarities and provided insights into inhibitor specificity. The novel bioinformatics and visualization methods presented in this study help suggest likely off-target inhibitor activities and polypharmacology strategies for drug makers.