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

Abstract

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.