Nature Cell Biology
1, 60 - 67 (1999)
doi:10.1038/9035
Indirubin, the active constituent of a Chinese antileukaemia medicine,
inhibits cyclin-dependent kinasesRalph Hoessel1, Sophie Leclerc2, Jane A. Endicott3, Martin E. M. Nobel3, Alison Lawrie3, Paul Tunnah3, Maryse Leost2, Eve Damiens2, 4, Dominique Marie2, 5, Doris Marko1, Ellen Niederberger1, Weici Tang1, Gerhard Eisenbrand1, 6
& Laurent Meijer21
Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin-Schrödinger-Strasse 52, 67663
Kaiserslautern, Germany
2
Cell Cycle Laboratory CNRS, Station Biologique, BP 74, 29682
Roscoff Cedex, Bretagne, France
3
University of Oxford, Laboratory of Molecular Biophysics, Department of Biochemistry and Oxford Centre for Molecular Sciences, South Parks Road, Oxford
OX1 3QU, UK
4
Université des Sciences et Technologies de Lille I, Laboratoire de Chimie Biologique, UMR 111 CNRS, 59655 Villeneuve d"Ascq Cedex, France
5
Phytoplankton Group, CNRS, Station Biologique, BP 74, 29682 Roscoff Cedex, Bretagne, France
6
eisenbra@rhrk.uni-kl.de
Correspondence should be addressed to Laurent Meijer meijer@sb-roscoff.frIndirubin 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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