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The Paullones: A Family of Pharmacological Inhibitors of Cyclin-Dependent Kinases and Glycogen Synthase Kinase 3

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Inhibitors of Protein Kinases and Protein Phosphates

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 167))

Abstract

Cyclin-dependent kinases (CDKs) regulate multiple pathways such as the cell division cycle, apoptosis, transcription, and neuronal functions. Glycogen synthase kinase 3 (GSK-3) plays a key role in Wnt signaling, cellular response to insulin, cell death, cell proliferation, maintenance of “stemness.” Both families of kinases are clearly involved in the onset and development of major human diseases like cancer, neurodegenerative disorders (Alzheimer’s and Parkinson’s disease, stroke), diabetes, restenosis, viral infections, etc. Homologues of these kinases also regulate the proliferation of unicellular parasites. For these reasons an intensive search for pharmacological inhibitors of these protein kinases has been carried out during the last decade. Numerous small molecular weight compounds have been described that directly compete with ATP for binding to the catalytic site of the kinases. We here illustrate the development of this research area by reviewing the paullones, a family of potent and rather selective inhibitors of CDKs and GSK-3, from their discovery and optimisation to their molecular and cellular characterisation. The potential medical applications of CDK/GSK-3 inhibitors are presented.

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Author information

Authors and Affiliations

  1. Cell Cycle Group and UPS-2682, C.N.R.S., Station Biologique, B.P. 74, 29682, Roscoff cedex, Bretagne, France

    L. Meijer, M. Leost, O. Lozach & S. Schmitt

  2. Institut für Pharmazie, Universität Hamburg, Bundesstraße 45, 20146, Hamburg, Germany

    C. Kunick

Authors
  1. L. Meijer
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  2. M. Leost
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  3. O. Lozach
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  4. S. Schmitt
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  5. C. Kunick
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Editor information

Editors and Affiliations

  1. Dipartimento di Chimica Biologica, Università di Padova, Via Trieste 75, Padova, 35121, Italy

    Lorenzo A. Pinna

  2. MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, MSI/WTB Complex, Dow St., Dundee, DD1 5EH, Scotland, UK

    Patricia T.W. Cohen Ph.D. (Professor of Molecular Biology) (Professor of Molecular Biology)

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Meijer, L., Leost, M., Lozach, O., Schmitt, S., Kunick, C. (2005). The Paullones: A Family of Pharmacological Inhibitors of Cyclin-Dependent Kinases and Glycogen Synthase Kinase 3. In: Pinna, L.A., Cohen, P.T. (eds) Inhibitors of Protein Kinases and Protein Phosphates. Handbook of Experimental Pharmacology, vol 167. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-26670-4_3

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