Ligand-based modeling followed by in vitro bioassay yielded new potent glucokinase activators

Glucokinase (GK) has received recent interest as a valid antidiabetic target. With this in mind, we applied a computational workflow based on combining pharmacophore modeling and QSAR analysis followed by in silico screening toward the discovery of novel GK activators. Virtual screening identified 10 promising bioactivators from the National Cancer Institute (NCI) list of compounds. The most potent NCI hit illustrated 6.3-fold GK activation at 10 mu M. These results demonstrated that our virtual screening protocol was able to identify novel GK activator leads for subsequent development into potential antidiabetic agents. (C) 2014 Elsevier Inc. All rights reserved.