Journal
MOLECULAR INFORMATICS
Volume 40, Issue 12, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/minf.202060031
Keywords
GSK-3 beta inhibitor; Alzheimer's disease; Virtual screening; Lead compound
Categories
Funding
- National Natural Science Foundation of China [81573281, 81830105, 81973207]
- Double First-Class initiative Innovation team project of China Pharmaceutical University [CPU2018GF11, CPU2018GY34]
Ask authors/readers for more resources
In this study, new GSK-3 beta inhibitors were identified through pharmacophore-based virtual screening. Four compounds showed inhibitory activity, with compounds 6 and 9 demonstrating good safety profiles. Compound 8 was identified as the preferred lead molecule for further development in treating Alzheimer's disease.
Glycogen synthase kinase 3 beta (GSK-3 beta) is considered as a promising drug target for the treatment of Alzheimer's disease (AD). In the present study, two compound libraries were selected for virtual screening based on pharmacophore models of GSK-3 beta to discover new inhibitors. Nine potential hits were retained for biological investigation and four of these compounds showed GSK-3 beta inhibitory activity (with the IC50 values in sub-micromolar range on GSK-3 beta). Compounds 6 and 9 have good safety. They do not have any significant in vitro cytotoxicity against PC12 and SH-SY5Y neuroblastoma cells at concentrations up to 90 mu M. Based on the inhibitory activity and druggability properties, compound 8 is the preferred molecule, and it is a promising lead for the development of the GSK-3 beta inhibitors for reducing the abnormal hyperphosphorylation of tau protein and relieving AD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available