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Anti-angiogenic potential of small molecular inhibitors of cyclin dependent kinases in vitro

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Abstract

Small molecular kinase inhibitors are promising novel drugs. Initially, they were designed for the highest possible specificity. Recently, this concept has been challenged by multikinase inhibitors, which are clinically more potent. This change of paradigm calls for re-examination of already known compounds in different functional contexts. We have compared 6 reported structurally different inhibitors of cyclin-dependent kinases (Cdks) regarding their functional effects on endothelial cells (proliferation, cell cycle, apoptosis, migration, tube formation), as well as their actions on some kinases (AKT, p38, ERK1/2, c-src, GSK3β). Only some of these compounds had anti-angiogenic effects in concentrations up to 10 μM (aminopurvalanol, indirubin-3′-monoxime, and alsterpaullone), depending on their kinase profile. Interestingly, the impact of the compounds on Cdks seemed to be of minor importance, as compared to other mechanisms. Aminopurvalanol, indirubin-3′-monoxime, and alsterpaullone might turn out as interesting scaffolds for the development of novel anti-angiogenic drugs.

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Acknowledgments

We thank Prof. L. Meijer (Roscoff, France) for supplying us with the Cdk compounds.

The authors gratefully acknowledge the expert technical assistance by C. Niemann, and J. Peliskova. This work was supported by a grant of the EC (FP6-2002-Life Sciences & Health, PRO-KINASE Research Project, Project no. LSHB-CT-2004-503467).

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  1. Department of Pharmacy, Center for System Based Drug Research, University of Munich, Butenandtstr. 5-13, 81377, Munich, Germany

    Stefan Zahler, Johanna Liebl, Robert Fürst & Angelika M. Vollmar

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  1. Stefan Zahler
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  2. Johanna Liebl
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  4. Angelika M. Vollmar
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Correspondence to Stefan Zahler.

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Zahler, S., Liebl, J., Fürst, R. et al. Anti-angiogenic potential of small molecular inhibitors of cyclin dependent kinases in vitro. Angiogenesis 13, 239–249 (2010). https://doi.org/10.1007/s10456-010-9181-1

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  • DOI: https://doi.org/10.1007/s10456-010-9181-1

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