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

Indirubin is the active ingredient of Danggui Longhui Wan, a mixture of pla nts that is used in traditional Chinese medicine to treat chronic diseases. Here we identify indirubin and its analogues as potent inhibitors of cycli n-dependent kinases (CDKs), The crystal structure of CDK2 in complex with i ndirubin derivatives shows that indirubin interacts with the kinase's ATP-b inding site through van der Waals interactions and three hydrogen bonds. In dirubin-3'-monoxime inhibits the proliferation of a large range of cells, m ainly through arresting the cells in the G2/M phase of the cell cycle. Thes e results have implications for therapeutic optimization of indigoids.