A novel GSK3 inhibitor that promotes self-renewal in mouse embryonic stem cells

Biosci Biotechnol Biochem. 2020 Oct;84(10):2113-2120. doi: 10.1080/09168451.2020.1789445. Epub 2020 Jul 8.


Small molecules that regulate cell stemness have the potential to make a major contribution to regenerative medicine. In the course of screening for small molecules that affect stemness in mouse embryonic stem cells (mESCs), we discovered that NPD13432, an aurone derivative, promoted self-renewal of mESCs. Normally, mESCs start to differentiate upon withdrawal of 2i/LIF. However, cells treated with the compound continued to express endogenous Nanog, a pluripotency marker protein essential for sustaining the undifferentiated state, even in the absence of 2i/LIF. Biochemical characterization revealed that NPD13432 inhibited GSK3α and GSK3β with IC50 values of 92 nM and 310 nM, respectively, suggesting that the compound promotes self-renewal in mESCs by inhibiting GSK3. The chemical structure of the compound is unique among known molecules with this activity, providing an opportunity to develop new inhibitors of GSK3, as well as chemical tools for investigating cell stemness.

Keywords: Aurone derivative; GSK3; embryonic stem cells; self-renewal.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Binding, Competitive
  • Cell Line
  • Cell Self Renewal / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Design
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / drug effects*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Glycogen Synthase / antagonists & inhibitors*
  • Glycogen Synthase / chemistry
  • Glycogen Synthase / metabolism
  • Mice
  • Molecular Docking Simulation
  • Protein Conformation


  • Enzyme Inhibitors
  • Adenosine Triphosphate
  • Glycogen Synthase