典型文献
Preclinical studies of the triazol0[1,5-a]pyrimidine derivative WS-716 as a highly potent,specific and orally active P-glycoprotein(P-gp)inhibitor
文献摘要：
Multidrug resistance(MDR)is the main cause of clinical treatment failure and poor prog-nosis in cancer.Targeting P-glycoprotein(P-gp)has been regarded as an effective strategy to overcome MDR.In this work,we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent,specific,and orally active P-gp inhibitor.Through direct binding to P-gp,WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel(PTX)in multiple resistant cell lines,without changing its expression or subcellular localization.WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid,induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells.In addition,WS-716 displayed minimal ef-fect on the drug-metabolizing enzyme cytochrome P4503A4(CYP3A4).Importantly,WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7％in patient-derived xenograft(PDX)models.Relative to PTX treatment alone,combination of WS-716 and PTX caused no obvious adverse reactions.Taken together,our preclinical studies revealed ther-apeutic promise of WS-716 against MDR cancer,the promising data warrant its further development for cancer therapy.
文献关键词：
中图分类号：
作者姓名：
Sai-Qi Wang;Qiu-Xu Teng;Shuai Wang;Zi-Ning Lei;Hui-Hui Hu;Hui-Fang Lv;Bei-Bei Chen;Jian-Zheng Wang;Xiao-Jing Shi;Wei-Feng Xu;Hong-Min Liu;Xiao-Bing Chen;Zhe-Sheng Chen;Bin Yu
作者机构：
Department of Oncology,the Affiliated Cancer Hospital of Zhengzhou University,Henan Cancer Hospital,Henan Cancer Institute,Zhengzhou 450008,China;State Key Laboratory of Esophageal Cancer Prevention&Treatment,Zhengzhou University,Zhengzhou 450052,China;College of Pharmacy and Health Sciences,St.John,s University,Queens,NY 11439,USA;School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001,China;Laboratory Animal Center,Academy of Medical Science,Zhengzhou University,Zhengzhou 450052,China
文献出处：
引用格式：
[1]Sai-Qi Wang;Qiu-Xu Teng;Shuai Wang;Zi-Ning Lei;Hui-Hui Hu;Hui-Fang Lv;Bei-Bei Chen;Jian-Zheng Wang;Xiao-Jing Shi;Wei-Feng Xu;Hong-Min Liu;Xiao-Bing Chen;Zhe-Sheng Chen;Bin Yu-.Preclinical studies of the triazol0[1,5-a]pyrimidine derivative WS-716 as a highly potent,specific and orally active P-glycoprotein(P-gp)inhibitor)[J].药学学报（英文版）,2022(08):3263-3280
A类：
triazol0,triazolo,Ad300
B类：
Preclinical,studies,pyrimidine,derivative,WS,highly,potent,orally,active,glycoprotein,gp,inhibitor,Multidrug,resistance,MDR,main,treatment,failure,poor,prog,nosis,cancer,Targeting,been,regarded,effective,strategy,overcome,In,this,work,we,reported,our,preclinical,compound,Through,direct,binding,inhibited,efflux,function,specifically,reversed,mediated,paclitaxel,PTX,multiple,resistant,lines,without,changing,its,expression,subcellular,localization,synergistically,formation,colony,spheroid,induced,apoptosis,cycle,arrest,G2,phase,SW620,cells,addition,displayed,minimal,metabolizing,enzyme,cytochrome,P4503A4,CYP3A4,Importantly,increased,sensitivity,both,clinically,derived,tumors,vivo,value,patient,xenograft,PDX,models,Relative,alone,combination,caused,obvious,adverse,reactions,Taken,together,revealed,apeutic,promise,against,promising,data,warrant,further,development,therapy
AB值：
0.582087
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