Physapubescin, a natural withanolide as a kidney-type glutaminase (KGA) inhibitor.
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.
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China; School of Traditional Chinese Materia Medica, Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Li
L
Cheng
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Can-Rong
CR
Wu
School of Traditional Chinese Materia Medica, Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Li-Han
LH
Zhu
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China; School of Traditional Chinese Materia Medica, Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: li_hua@hust.edu.cn.
Hua
H
Li
School of Traditional Chinese Materia Medica, Wuya College of Innovation, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: syzyclx@163.com.
Li-Xia
LX
Chen
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001681:Biological Assay; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D005972:Glutaminase / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D007668:Kidney / Q000201:enzymology; D008024:Ligands; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D019657:Solanaceae / Q000737:chemistry; D054358:Withanolides / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D008024:Ligands; D054358:Withanolides; C586239:physapubescin; D005972:Glutaminase
Cytotoxicity; Enzyme inhibition; KGA inhibitor; Physapubescin; Structure-based virtual ligand screening