Novel GSK-3β inhibitors from sequential virtual screening

Hye Jung Kim, Hyunah Choo, Yong Seo Cho, Kyoung Tai No, Ae Nim Pae

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Glycogen synthase kinase-3 (GSK-3β) has been emerging as a key therapeutic target for type-2 diabetics, Alzheimer's disease, cancer, and chronic inflammation. For the purpose of finding biologically active and novel compounds and providing new idea for drug-design, we performed virtual screening using commercially available database. Three-dimensional common feature pharmacophore model was developed by using HipHop program provided in Catalyst software and it was used as a query for screening database. Recursive partitioning (RP) model was developed as a filtering system, which was able to classify active and inactive compounds. Eventually, a sequential virtual screening procedure (SQSP) was conducted by applying the common feature pharmacophore and RP model in succession to discover novel potent GSK-3β inhibitors. The final 56 hit compounds were carefully selected considering predicted docking mode in crystal structures. Subsequent enzyme assay for human GSK-3β protein confirmed that three compounds of these hit compounds exhibit micromolar inhibitory activity. Here, we report novel hit compounds and their binding mode in the active site of GSK-3β crystal structure.

Original languageEnglish
Pages (from-to)636-643
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number2
DOIs
Publication statusPublished - 2008 Jan 15

Fingerprint

Glycogen Synthase Kinase 3
Screening
Crystal structure
Databases
Drug Design
Enzyme Assays
Assays
Catalytic Domain
Software
Inflammation
Catalysts
Enzymes
Pharmaceutical Preparations
Neoplasms
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Kim, Hye Jung ; Choo, Hyunah ; Cho, Yong Seo ; No, Kyoung Tai ; Pae, Ae Nim. / Novel GSK-3β inhibitors from sequential virtual screening. In: Bioorganic and Medicinal Chemistry. 2008 ; Vol. 16, No. 2. pp. 636-643.
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Novel GSK-3β inhibitors from sequential virtual screening. / Kim, Hye Jung; Choo, Hyunah; Cho, Yong Seo; No, Kyoung Tai; Pae, Ae Nim.

In: Bioorganic and Medicinal Chemistry, Vol. 16, No. 2, 15.01.2008, p. 636-643.

Research output: Contribution to journalArticle

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