Laboratoire d'Ingénierie Moléculaire et Biochimie Pharmacologique, Institut Jean Barriol, Université Paul Verlaine, FR CNRS 2843, 1 Boulevard Arago, 57070 Metz, France.
Bioorg Med Chem Lett. 2010 Oct 1;20(19):5827-30. doi: 10.1016/j.bmcl.2010.07.130. Epub 2010 Aug 3.
The cell division cycle 25 (Cdc25) family of proteins are dual specificity phosphatases that activate cyclin-dependent kinase (CDK) complexes, which in turn regulate progression through the cell division cycle. Overexpression of Cdc25 proteins has been reported in a wide variety of cancers; their inhibition may thus represent a novel approach for the development of anticancer therapeutics. Herein we report new coumarin-based scaffolds endowed with a selective inhibition against Cdc25A and Cdc25C, being 6a and 6d the most efficient inhibitors and worthy of further investigation as anticancer agents.
细胞周期蛋白依赖性激酶（CDK）复合物的激活物细胞分裂周期 25（Cdc25）家族蛋白是双特异性磷酸酶，它们反过来调节细胞分裂周期的进展。已报道在各种癌症中过度表达 Cdc25 蛋白；因此，抑制它们可能代表开发抗癌治疗的新方法。在此，我们报告了具有选择性抑制 Cdc25A 和 Cdc25C 的新型香豆素基支架，其中 6a 和 6d 是最有效的抑制剂，值得进一步研究作为抗癌剂。
