Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases

被引:746
作者
Hoessel, R
Leclerc, S
Endicott, JA
Nobel, MEM
Lawrie, A
Tunnah, P
Leost, M
Damiens, E
Marie, D
Marko, D
Niederberger, E
Tang, WC
Eisenbrand, G
Meijer, L
机构
[1] CNRS, Biol Stn, Cell Cycle Lab, F-29682 Roscoff, Bretagne, France
[2] Univ Kaiserslautern, Dept Chem, Div Food Chem & Environm Toxicol, D-67663 Kaiserslautern, Germany
[3] CNRS, Biol Stn, Phytoplankton Grp, F-29682 Roscoff, Bretagne, France
[4] Univ Oxford, Dept Biochem, Lab Mol Biophys, Oxford OX1 3QU, England
[5] Oxford Ctr Mol Sci, Oxford OX1 3QU, England
[6] Univ Lille 1, Chim Biol Lab, CNRS, UMR 111, F-59655 Villeneuve Dascq, France
基金
英国生物技术与生命科学研究理事会; 英国医学研究理事会;
关键词
D O I
10.1038/9035
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Indirubin is the active ingredient of Danggui Longhui Wan, a mixture of plants that is used in traditional Chinese medicine to treat chronic diseases. Here we identify indirubin and its analogues as potent inhibitors of cyclin-dependent kinases (CDKs), The crystal structure of CDK2 in complex with indirubin derivatives shows that indirubin interacts with the kinase's ATP-binding site through van der Waals interactions and three hydrogen bonds. Indirubin-3'-monoxime inhibits the proliferation of a large range of cells, mainly through arresting the cells in the G2/M phase of the cell cycle. These results have implications for therapeutic optimization of indigoids.
引用
收藏
页码:60 / 67
页数:8
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