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.

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A series of low molecular compounds from Chinese herbal medicines which have proved to be, in some cases, highly effective especially in tumor therapy, is listed here (part II will deal with high molecular compounds, to be published in the next issue). In contrast to synthetic agents used in cancer chemotherapy, these natural compounds have relatively low toxicities. Many of the clinical studies referred to in this paper have been carried out on Asians. Because genetic factors influence enzyme levels, sometimes leading to striking differences in metabolism and pharmacokinetics of drugs, results obtained in clinical studies carried out in China are not 100 % transferable to the European population. The mechanisms of action of these compounds are manifold, consisting of reactions with DNA bases, intercalation in DNA, inhibition of topoisomerases, inhibition of protein kinases, induction of apoptosis etc. Some of the compounds have interesting structural features, that may be used as lead structures for the development of further antitumor agents.