IRC‐083864, a novel bis quinone inhibitor of CDC25 phosphatases active against human cancer cells |
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| Authors: | Marie‐Christine Brezak Annie Valette Muriel Quaranta Marie‐Odile Contour‐Galcera Denis Jullien Olivier Lavergne Céline Frongia Dennis Bigg Philip G. Kasprzyk Grégoire Pierre Prevost Bernard Ducommun |
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| Affiliation: | 1. IPSEN, Institut Henri Beaufour, 5 Avenue du Canada, Les Ulis, France;2. LBCMCP‐CNRS UMR5088, University of Toulouse, 118 Route de Narbonne, Toulouse, France;3. IPSEN, Biomeasure, Milford, MA;4. CHU Purpan, TSA 40031, Toulouse Cedex, France;5. Fax: +3‐356‐155‐8109. |
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| Abstract: | CDC25 phosphatases are key actors in cyclin‐dependent kinases activation whose role is essential at various stages of the cell cycle. CDC25 expression is upregulated in a number of human cancers. CDC25 phosphatases are therefore thought to represent promising novel targets in cancer therapy. Here, we report the identification and the characterization of IRC‐083864, an original bis‐quinone moiety that is a potent and selective inhibitor of CDC25 phosphatases in the low nanomolar range. IRC‐083864 inhibits cell proliferation of a number of cell lines, regardless of their resistance to other drugs. It irreversibly inhibits cell proliferation and cell cycle progression and prevents entry into mitosis. In addition, it inhibits the growth of HCT‐116 tumor spheroids with induction of p21 and apoptosis. Finally, IRC‐083864 reduced tumor growth in mice with established human prostatic and pancreatic tumor xenografts. This study describes a novel compound, which merits further study as a potential anticancer agent. © 2008 Wiley‐Liss, Inc. |
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| Keywords: | CDC25 phosphatase cell cycle cancer pharmacology |
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