SP600125,a selective JNK inhibitor,is a potent inhibitor of NAD(P)H:quinone oxidoreductase 1(NQO1)  

作　　者：Bing-ling Zhong Yi-fei Zhang Hao-yi Zheng Qiang Chen Hua-dong Lu Xiu-ping Chen 

机构地区：[1]State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macao,Macao,China [2]Faculty of Health Sciences,University of Macao,Macao,China [3]MoE Frontiers Science Center for Precision Oncology,University of Macao,Macao,China [4]Department of Pathology,Zhongshan Hospital(Xiamen),Fudan University,Xiamen Clinical Research Center for Cancer Therapy,Xiamen,361015,China

出　　处：《Acta Pharmacologica Sinica》2025年第4期1137-1144,共8页中国药理学报(英文版)

基　　金：supported by the Science and Technology Development Fund of Macao SAR(0070/2022/A2,0081/2021/A2);the Research Fund of University of Macao(MYRG-GRG2023-00072-ICMS-UMDF);the Ministry of Education Frontiers Science Center for Precision Oncology,University of Macao(SP2023-00001-FSCPO).

摘　　要：The c-Jun N-terminal kinases(JNKs)has been identified as a critical modulator in multiple cellular processes,including stress stimulus,inflammation,cell proliferation,apoptosis,etc.SP600125 is a widely used ATP-competitive reversible JNKs inhibitor.NAD(P)H:quinone oxidoreductase 1(NQO1)is a flavoprotein mediated two or four electron-reduction of quinones.Here,we showed that SP600125 bind to the active pocket of NQO1 and inhibit NQO1 activity.SP600125 exhibits comparable inhibitory effects on NQO1-mediated quinone bioactivation,H2O2 generation,and cell death,as the specific NQO1 inhibitor dicoumarol(DIC).Importantly,the inhibitory effects of SP600125 on NQO1 are independent of JNKs inhibition.These results suggested that SP600125 is a novel NQO1 inhibitor,which provides new insights into the mechanism of action of SP600125.Furthermore,SP600125 should be used more cautiously as a JNKs inhibitor,especially when NQO1 is highly expressed.

关 键 词：SP600125 JNK NQO1 

分 类 号：R96[医药卫生—药理学]