| Comparative Virtual and Experimental High-Throughput Screening for Glycogen Synthase Kinase-3β Inhibitors |
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Presentation: P01017 Session: Cheminformatics, Library Design and Virtual HTS - Poster SessionTímea Polgár, Andrea Baki, Györgyi I. Szendrei and György M. Keser, Richetr Gedeon Ltd Presenting Author: Timea Polgar, Richter Gedeon Ltd - Hungary Glycogen synthase kinase-3β is a serine/threonine kinase that has recently emerged as a key target for neurodegenerative diseases and diabetes. As an initial step of our lead discovery program we developed a virtual screen to discriminate known GSK-3β inhibitors and inactive compounds using FlexX, FlexX-Pharm and FlexE. The maximal enrichment factor (EF=28) at 1% of the screening library suggests that our protocol identifies potential GSK-3β inhibitors effectively from large compound collections. The effectiveness of our screening protocol was further investigated by a comparative experimental and virtual high-throughput screen performed for the same subset of our corporate library. Enrichment factors, the significantly higher hit rate of virtual screening (vHTS:12.9%, HTS: 0.055%) and also the comparison of active clusters suggest that our virtual screening protocol is an effective tool in GSK-3β-based library focusing. Head-to-head comparison of true/false positives and negatives, however, revealed the two approaches to be complementary rather than competitive. |