Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Bioorg Med Chem Lett. 2009 Nov 1;19(21):6233-6. doi: 10.1016/j.bmcl.2009.08.090. Epub 2009 Sep 1.
Small molecules that mimic the transcriptional activation domain of eukaryotic transcriptional activators have the potential to serve as effective inhibitors of transcriptional processes. Here we show that one class of transcriptional activation domain mimics, amphipathic isoxazolidines, can be converted into inhibitors of gene expression mediated by the transcriptional activator ESX through small structural modifications. Addition of the small molecules leads to decreased expression of the cell surface growth receptor ErbB2(Her2) in ErbB2-positive cancer cells and, correspondingly, decreased proliferation.
小分子模拟真核转录激活因子的转录激活结构域，具有作为转录过程有效抑制剂的潜力。在这里，我们表明，一类转录激活结构域模拟物，两亲性异恶唑烷，可以通过小的结构修饰转化为转录激活因子 ESX 介导的基因表达抑制剂。小分子的添加导致 ErbB2 阳性癌细胞表面生长受体 ErbB2(Her2)表达降低，相应地，增殖减少。
