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

Lookup NU author(s): Professor Jane Endicott, Professor Martin Noble

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Abstract

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.


Publication metadata

Author(s): Hoessel R, Leclerc S, Endicott JA, Noble MEM, Lawrie A, Tunnah P, Leost M, Damiens E, Marie D, Marko D, Niederberger E, Tang WC, Eisenbrand G, Meijer L

Publication type: Article

Publication status: Published

Journal: Nature cell biology

Year: 1999

Volume: 1

Issue: 1

Pages: 60-67

Print publication date: 01/05/1999

ISSN (print): 1465-7392

ISSN (electronic): 1476-4679

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/9035

DOI: 10.1038/9035


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