2. Academic Validation
  3. Discovery of new GSK-3β inhibitors through structure-based virtual screening

Discovery of new GSK-3β inhibitors through structure-based virtual screening

  • Bioorg Med Chem Lett. 2018 Jan 15;28(2):160-166. doi: 10.1016/j.bmcl.2017.11.036.
Xiaodong Dou 1,  Lan Jiang 1,  Yanxing Wang 1,  Hongwei Jin 1,  Zhenming Liu 2,  Liangren Zhang 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
  • 2 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: zmliu@bjmu.edu.cn.
  • 3 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China. Electronic address: liangren@bjmu.edu.cn.
PMID: 29208522 DOI: 10.1016/j.bmcl.2017.11.036
Abstract

Glycogen synthase kinase-3β (GSK-3β) is an attractive therapeutic target for human diseases, such as diabetes, Cancer, neurodegenerative diseases, and inflammation. Thus, structure-based virtual screening was performed to identify novel scaffolds of GSK-3β inhibitors, and we observed that conserved water molecules of GSK-3β were suitable for virtual screening. We found 14 hits and D1 (IC50 of 0.71 μM) were identified. Furthermore, the neuroprotection activity of D1-D3 was validated on a cellular level. 2D similarity searches were used to find derivatives of high inhibitory compounds and an enriched structure-activity relationship suggested that these skeletons were worthy of study as potent GSK-3β inhibitors.

Keywords

2D similarity search; GSK-3β; Molecular dynamics; Radiometric assay; Virtual screening.

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