Optimization of a small molecule probe that restores e-cadherin expression.
Optimization of a small molecule probe that restores e-cadherin expression.
复制标题
恢复 e-钙粘蛋白表达的小分子探针的优化。
DOI：
10.1016/j.bmcl.2015.07.104
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发表时间：
2015
影响因子：
2.7
通讯作者：
Waterson,AlexG
中科院分区：
文献类型：
--
作者：
Brogan,JohnT;Stoops,SydneyL;Brady,Suzanne;An,Hanbing;Weaver,Connie;Daniels,JScott;Beauchamp,RDaniel;Lindsley,CraigW;Waterson,AlexG
E-钙粘蛋白是一种普遍存在的跨膜蛋白，在细胞接触中具有重要功能，并已被证明在上皮间质转化中发挥作用。我们先前已经报道了使用HTS筛选来鉴定能够在癌细胞中恢复e-钙粘蛋白的化合物。在这里，我们报告了这些分子的额外药物化学优化，导致在低微摩尔浓度下恢复e-钙粘蛋白表达的新分子。此外，我们报告了初步的药物动力学数据的化合物，ML 327，可用作探针的e-钙粘蛋白恢复。
E-cadherin is a ubiquitous trans-membrane protein that has important functions in cellular contacts and has been shown to play a role in the epithelial mesenchymal transition. We have previously reported the use of an HTS screen to identify compounds that are capable of restoring e-cadherin in cancer cells. Here, we report the additional medicinal chemistry optimization of these molecules, resulting in new molecules that restore e-cadherin expression at low micromolar concentrations. Further, we report preliminary pharmacokinetic data on a compound, ML327, that can be used as a probe of e-cadherin restoration.