| Autor: |
Polgar, T., Baki, A., Szendrei, G. I., Keseruu, G. M. |
| Zdroj: |
Journal of Medicinal Chemistry; December 2005, Vol. 48 Issue: 25 p7946-7959, 14p |
| Abstrakt: |
Glycogen synthase kinase-3β (GSK-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) suggests that our protocol identifies potential GSK-3β inhibitors effectively from large compound collections. The effectiveness of our screening protocol was further investigated by comparative experimental and virtual high-throughput screens (HTSs) performed for the same subset of our corporate library. Enrichment factors, the significantly higher hit rate of virtual screening (12.9%) than that of the HTS (0.55%), 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 revealed the two approaches to be complementary rather than competitive. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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