[1]李 根,赵 栋,李 健,等.端锚聚合酶作为药物靶点的研究进展[J].中国药理学通报,2018,(09):1206-1210.[doi:10.3969/j.issn.1001-1978.2018.09.006]
 LI Gen,ZHAO Dong,LI Jian,et al.Research progress of TNKS as drug target[J].Chinese Pharmacological Bulletin,2018,(09):1206-1210.[doi:10.3969/j.issn.1001-1978.2018.09.006]
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端锚聚合酶作为药物靶点的研究进展()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2018年09期
页码:
1206-1210
栏目:
讲座与综述
出版日期:
2018-09-26

文章信息/Info

Title:
Research progress of TNKS as drug target
文章编号:
1001-1978(2018)09-1206-05
作者:
李 根1赵 栋2李 健13尹秀山14张万忠1
1.沈阳化工大学制药与生物工程学院,辽宁 沈阳 110142; 2.西安医学院基础与转化医学研究所,陕西 西安 710021; 3.肯塔基大学药学院,美国 列克星敦 40536; 4.卡罗林斯卡医学院微生物,肿瘤与细胞研究所,瑞典 斯德哥尔摩 17165
Author(s):
LI Gen1 ZHAO Dong2 LI Jian13 YIN Xiu-shan14ZHANG Wan-zhong1
1.College of Pharmaceutical and Biological Engineering,Shenyang University of Chemical Technology,Shenyang 110142,China; 2.Institute of Basic and Translational Medicine,Xi'an Medical University, Xi'an 710021,China; 3.Dept of Molecular & Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY 40536, USA; 4.Karolinska Institutet(MTC), Science for Life Lab, Tomtebodavägen, en 23A(Gamma5), 17165 Solna, Sweden
关键词:
TNKS PARP家族 细胞功能调节 聚ADP-核糖基化 药物靶点 抑制剂
Keywords:
TNKS PARP family regulation of cell function poly(ADP-ribosylation) drug target inhibitor
分类号:
R-05; R329.24; R345.5; R977.3
DOI:
10.3969/j.issn.1001-1978.2018.09.006
文献标志码:
A
摘要:
端锚聚合酶(TNKS)属于聚腺苷二磷酸核糖聚合酶家族。TNKS与PARP家族的其它成员不同,它们具有两个独特的结构:SAM结构域和锚蛋白重复区。TNKS参与多种细胞功能调节,其中包括端粒的动态平衡、Wnt信号通路、葡萄糖代谢和有丝分裂期间纺锤体的形成等。TNKS主要通过聚ADP-核糖基化[poly(ADP-ribosylation),PARs]调节靶蛋白的稳定性来发挥作用。因此,TNKS的催化结构域是一个很有潜力的药物靶点。近年来,已有多个针对PARP家族的抑制剂进入不同的临床评估阶段,阿斯利康公司的奥拉帕尼、Clovis公司的瑞卡帕尼和默沙东公司的尼拉帕尼均已上市。该文对TNKS的结构、功能和抑制剂的研究现状进行概述。
Abstract:
TNKSs are members of poly(ADPribose)polymerases, which are different from other members of the PARP family with two unique structures: SAM domain and ankyrin repeat region. TNKS participates in a variety of cellular function regulation, including telomere's dynamic balance, Wnt signaling pathways, glucose metabolism and spindle formation during mitosis. TNKS, as a very attractive drug target, regulates the stability of target proteins via poly(ADP-ribosylation). In recent years, the significant progress has been made for PARP inhibitors in cancer treatment. Multiple PARP inhibitors have entered different clinical evaluation stages. AstraZeneca's Olaparib, Clovis's Rucaparib, Merck's Niraparib come into existence in the market. This paper summarizes the recent studies of TNKS and its related inhibitors.

参考文献/References:

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备注/Memo

备注/Memo:
收稿日期:2018-04-15,修回日期:2018-05-28
基金项目:国家自然科学基金资助项目(No 81402850); 西安医学院青年科研基金项目(2016QN32)
作者简介:李 根(1994-),男,硕士生,研究方向:结构生物学,E-mail:2473750500@qq.com;
张万忠(1968-),男,硕士,教授,研究方向:生物分离工程,通讯作者,E-mail:lzwz2004@sina.com;
尹秀山(1981-),男,博士,教授,研究方向:结构生物学与干细胞,通讯作者,E-mail: xiushanyin@gmail.com
更新日期/Last Update: 2018-08-26