Amphipathic benzenes are designed inhibitors of the estrogen receptor α/steroid receptor coactivator interaction
Amphipathic benzenes are designed inhibitors of the estrogen receptor α/steroid receptor coactivator interaction
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DOI：
10.1021/cb800056r
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发表时间：
2008-05-01
影响因子：
4
通讯作者：
Katzenettenbogen, John A.
中科院分区：
文献类型：
--
作者：
Gunther, Jillian R.;Moore, Terry W.;Katzenettenbogen, John A.
我们在这里报告的设计，合成和评价的小分子抑制剂之间的相互作用的类固醇受体辅激活剂和雌激素受体α。这些抑制剂基于两亲性苯支架，其疏水面模拟类固醇受体辅激活剂上的富含亮氨酸的α-螺旋共有序列，其与雌激素受体α上的浅沟相互作用。这些分子中的几种是迄今为止描述的这种相互作用的最有效的抑制剂，并且在雌激素受体作用的体外模型和雌激素受体介导的共激活因子相互作用和转录的基于细胞的测定中在低微摩尔浓度下是有活性的。
We report here on the design, synthesis, and evaluation of small molecule inhibitors of the interaction between a steroid receptor coactivator and estrogen receptor alpha. These inhibitors are based upon an amphipathic benzene scaffold whose hydrophobic face mimics the leucine-rich alpha-helical consensus sequence on the steroid receptor coactivators that interacts with a shallow groove on estrogen receptor alpha. Several of these molecules are among the most potent inhibitors of this interaction described to date and are active at low micromolar concentrations in both in vitro models of estrogen receptor action and in cell-based assays of estrogen receptor-mediated coactivator interaction and transcription.