Physapubescin, a natural withanolide as a kidney-type glutaminase (KGA) inhibitor

Bioorg Med Chem Lett. 2017 Mar 1;27(5):1243-1246. doi: 10.1016/j.bmcl.2017.01.057. Epub 2017 Jan 21.


Kidney-type glutaminase (KGA) is over expressed in many kinds of cancers that converts glutamine to glutamate for supplying energy, and has become an object for targeted cancer therapy. The structure-based virtual ligand screening identified physapubescin, a withanolide purified from Physalis pubescens L., as a possible inhibitor of KGA with low binding energy. Enzyme inhibition experiments and cell-based assays further confirmed its inhibitory effects on KGA activity, suggesting potential applications of physapubescin and its derivatives as KGA inhibitors.

Keywords: Cytotoxicity; Enzyme inhibition; KGA inhibitor; Physapubescin; Structure-based virtual ligand screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Biological Assay
  • Cell Line, Tumor
  • Enzyme Activation / drug effects
  • Glutaminase / antagonists & inhibitors*
  • Humans
  • Inhibitory Concentration 50
  • Kidney / enzymology
  • Ligands
  • Molecular Docking Simulation
  • Molecular Structure
  • Solanaceae / chemistry
  • Withanolides / chemistry
  • Withanolides / pharmacology*


  • Antineoplastic Agents
  • Ligands
  • Withanolides
  • physapubescin
  • Glutaminase