典型文献
A potent PGK1 antagonist reveals PGK1 regulates the production of IL-1β and IL-6
文献摘要：
Glycolytic metabolism enzymes have been implicated in the immunometabolism field through changes in metabolic status.PGK1 is a catalytic enzyme in the glycolytic pathway.Here,we set up a high-throughput screen platform to identify PGK1 inhibitors.DC-PGKI is an ATP-competitive inhibitor of PGK1 with an affinity of Kd=99.08 nmol/L.DC-PGKI stabilizes PGK1 in vitro and in vivo,and suppresses both glycolytic activity and the kinase function of PGK1.In addition,DC-PGKI unveils that PGK1 regulates production of IL-1β and IL-6 in LPS-stimulated macrophages.Mechanistically,inhibition of PGK1 with DC-PGKI results in NRF2(nuclear factor-erythroid factor 2-related factor 2,NFE2L2)accumulation,then NRF2 translocates to the nucleus and binds to the prox-imity region of Il-1β and Il-6 genes,and inhibits LPS-induced expression of these genes.DC-PGKI ame-liorates colitis in the dextran sulfate sodium(DSS)-induced colitis mouse model.These data support PGK1 as a regulator of macrophages and suggest potential utility of PGK1 inhibitors in the treatment of inflammatory bowel disease.
文献关键词：
中图分类号：
作者姓名：
Liping Liao;Wenzhen Dang;Tingting Lin;Jinghua Yu;Tonghai Liu;Wen Li;Senhao Xiao;Lei Feng;Jing Huang;Rong Fu;Jiacheng Li;Liping Liu;Mingchen Wang;Hongru Tao;Hualiang Jiang;Kaixian Chen;Xingxing Diao;Bing Zhou;Xiaoyan Shen;Cheng Luo
作者机构：
State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;University of Chinese Academy of Sciences,Beijing 100049,China;Department of Pharmacology&the Key Laboratory of Smart Drug Delivery,Ministry of Education,School of Pharmacy,Fudan University,Shanghai 201203,China;School of Pharmaceutical Science and Technology,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Hangzhou 310024,China;School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,China
文献出处：
引用格式：
[1]Liping Liao;Wenzhen Dang;Tingting Lin;Jinghua Yu;Tonghai Liu;Wen Li;Senhao Xiao;Lei Feng;Jing Huang;Rong Fu;Jiacheng Li;Liping Liu;Mingchen Wang;Hongru Tao;Hualiang Jiang;Kaixian Chen;Xingxing Diao;Bing Zhou;Xiaoyan Shen;Cheng Luo-.A potent PGK1 antagonist reveals PGK1 regulates the production of IL-1β and IL-6)[J].药学学报（英文版）,2022(11):4180-4192
A类：
Glycolytic,PGKI,liorates
B类：
PGK1,antagonist,reveals,regulates,production,enzymes,have,been,implicated,immunometabolism,field,changes,metabolic,status,catalytic,glycolytic,pathway,Here,set,high,throughput,screen,platform,identify,inhibitors,DC,ATP,competitive,affinity,Kd,nmol,stabilizes,vitro,vivo,suppresses,both,activity,kinase,function,In,addition,unveils,that,LPS,stimulated,macrophages,Mechanistically,inhibition,results,NRF2,nuclear,erythroid,related,NFE2L2,accumulation,then,translocates,nucleus,binds,prox,imity,region,Il,genes,inhibits,induced,expression,these,ame,colitis,dextran,sulfate,sodium,DSS,mouse,model,These,data,support,regulator,suggest,potential,utility,treatment,inflammatory,bowel,disease
AB值：
0.544852
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