Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Eur J Med Chem. 2012 Aug;54:188-96. doi: 10.1016/j.ejmech.2012.04.041. Epub 2012 May 14.
A number of selective estrogen receptor modulators (SERMs) were discovered from the SPECS database via a simple protocol. Based on two reference SERMs we identified via structure-based virtual screening previously, ligand-based similarity search and molecular docking filtering were conducted to identify novel SERMs from SPECS library. Among the 36 purchased compounds, 21 were confirmed to be active by in vitro assays, and 10 showed dual profile properties, namely as antagonists of ERα and agonists of ERβ. The anti-proliferative potency of these ligands was also evaluated against MCF-7 cell lines. Further investigation of the anti-proliferative mechanism of compound 3a suggested that it induced a G1 cell cycle arrest in ERα positive MCF-7 cell through ERα mediated cyclin D1 down-regulation.
从 SPECS 数据库中，通过一个简单的方案，发现了一些选择性雌激素受体调节剂（SERMs）。基于我们之前通过基于结构的虚拟筛选鉴定的两种参考 SERMs，进行了基于配体的相似性搜索和分子对接过滤，以从 SPECS 文库中鉴定新的 SERMs。在购买的 36 种化合物中，有 21 种通过体外测定被证实具有活性，其中 10 种显示出双重特性，即 ERα 的拮抗剂和 ERβ 的激动剂。这些配体的抗增殖活性也针对 MCF-7 细胞系进行了评估。对化合物 3a 的抗增殖机制的进一步研究表明，它通过 ERα 介导的细胞周期蛋白 D1 下调诱导 ERα 阳性 MCF-7 细胞中的 G1 细胞周期停滞。
