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Abstract
The cell division cycle 25 phosphatases (CDC25A, B, and C; E.C. 3.1.3.48) are key regulator of the cell cycle in human cells. Their aberrant expression has been associated with the insurgence and development of various types of cancer, and with a poor clinical prognosis. Therefore, CDC25 phosphatases are a valuable target for the development of small molecule inhibitors of therapeutic relevance. Here, we used an integrated strategy mixing organic chemistry with biological investigation and molecular modeling to study novel quinonoid derivatives as CDC25 inhibitors. The most promising molecules proved to inhibit CDC25 isoforms at single digit micromolar concentration, becoming valuable tools in chemical biology investigations and profitable leads for further optimization.
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Details
1 Pôle Chimie Et Physique Moléculaire, UMR CNRS 7565, Laboratoire Structure et Réactivite des Systèmes Moléculaires Complexes, Université de Lorraine, Metz, France;
2 Ecole Européenne de Chimie, Polymères et Matériaux (ECPM), Laboratoire de Synthèse et Catalyze (UMR CNRS 7509), Université de Strasbourg, Strasbourg, France;
3 ICMMO, Université Orsay Cedex, France;
4 Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Roma, Rome, Italy;; Istituto Italiano di Tecnologia, Center for Life Nano Science@Sapienza, Rome, Italy
5 Istituto Italiano di Tecnologia, Center for Life Nano Science@Sapienza, Rome, Italy
6 Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Roma, Rome, Italy;