Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases
Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases
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DOI：
10.1038/9035
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发表时间：
1999-05-01
影响因子：
21.3
通讯作者：
Meijer, L
中科院分区：
文献类型：
--
作者：
Hoessel, R;Leclerc, S;Meijer, L
靛玉红是当归龙回丸的活性成分，当归龙回丸是一种植物混合物，用于中医治疗慢性疾病。靛玉红及其类似物是细胞周期蛋白依赖性激酶（CDK）的有效抑制剂。CDK 2与靛玉红衍生物复合物的晶体结构表明靛玉红通过货车德瓦尔斯相互作用和三个氢键与激酶的ATP结合位点相互作用。靛玉红-3 '-单肟主要通过将细胞阻滞在细胞周期的G2/M期来抑制大范围细胞的增殖。这些结果对靛蓝类化合物的治疗优化具有影响。
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.