典型文献
Design,synthesis and pharmacological characterization of N-(3-ethylbenzo[d]isoxazol-5-yl)sulfonamide derivatives as BRD4 inhibitors against acute myeloid leukemia
文献摘要：
BRD4 plays a key role in the regulation of gene transcription and has been identified as an attractive target for cancer treatment.In this study,we designed 26 new compounds by modifying 3-ethyl-benzo[d]isoxazole core with sulfonamides.Most compounds exhibited potent BRD4 binding activities with △Tm values exceeding 6℃.Two crystal structures of 11h and 11r in complex with BRD4(1)were obtained to characterize the binding patterns.Compounds 11 h and 11r were effective for BRD4(1)binding and showed remarkable anti-proliferative activity against MV4-11 cells with IC50 values of 0.78 and 0.87 μM.Furthermore,11r(0.5-10μM)concentration-dependently inhibited the expression levels of oncogenes including c-Myc and CDK6 in MV4-11 cells.Moreover,11r(0.5-10 μM)concentration-dependently blocked cell cycle in MV4-11 cells at G0/G1 phase and induced cell apoptosis.Compound 11r may serve as a new lead compound for further drug development.
文献关键词：
中图分类号：
作者姓名：
Mao-feng Zhang;Xiao-yu Luo;Cheng Zhang;Chao Wang;Xi-shan Wu;Qiu-ping Xiang;Yong Xu;Yan Zhang
作者机构：
College of Pharmacy,Taizhou Polytechnic College,Taizhou 225300,China;Guangzhou Younan Technology Co.,Ltd,Guangzhou 510663,China;Center for Chemical Biology and Drug Discovery,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China;University of Chinese Academy of Sciences,Beijing 100049,China;State Key Laboratory of Respiratory Disease,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou 510530,China;China-New Zealand Joint Laboratory on Biomedicine and Health,Guangzhou 510530,China
文献出处：
引用格式：
[1]Mao-feng Zhang;Xiao-yu Luo;Cheng Zhang;Chao Wang;Xi-shan Wu;Qiu-ping Xiang;Yong Xu;Yan Zhang-.Design,synthesis and pharmacological characterization of N-(3-ethylbenzo[d]isoxazol-5-yl)sulfonamide derivatives as BRD4 inhibitors against acute myeloid leukemia)[J].中国药理学报（英文版）,2022(10):2735-2748
A类：
ethylbenzo,isoxazol,isoxazole,11r
B类：
Design,synthesis,pharmacological,characterization,derivatives,BRD4,inhibitors,against,acute,myeloid,leukemia,plays,key,role,regulation,transcription,been,identified,attractive,target,cancer,treatment,In,this,study,designed,new,compounds,by,modifying,core,sulfonamides,Most,exhibited,potent,binding,activities,Tm,values,exceeding,Two,crystal,structures,11h,complex,were,obtained,characterize,patterns,Compounds,effective,showed,remarkable,anti,proliferative,activity,MV4,cells,IC50,Furthermore,concentration,dependently,inhibited,expression,levels,oncogenes,including,Myc,CDK6,Moreover,blocked,cycle,G0,G1,phase,induced,apoptosis,may,serve,lead,further,drug,development
AB值：
0.56297
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