Semi-automated high-throughput fluorescent intercalator displacement-based discovery of cytotoxic DNA binding agents from a large compound library.
Semi-automated high-throughput fluorescent intercalator displacement-based discovery of cytotoxic DNA binding agents from a large compound library.
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DOI：
10.1016/j.bmcl.2010.01.033
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发表时间：
2010-03-01
影响因子：
2.7
通讯作者：
Long, Eric C.
中科院分区：
文献类型：
--
作者：
Glass, LaTeca S.;Bapat, Aditi;Kelley, Mark R.;Georgiadis, Millie M.;Long, Eric C.
High-throughput fluorescent intercalator displacement (HT-FID) was adapted to the semi-automated screening of a commercial compound library containing 60,000 molecules resulting in the discovery of cytotoxic DNA-targeted agents. Although commercial libraries are routinely screened in drug discovery efforts, the DNA binding potential of the compounds they contain has largely been overlooked. HT-FID led to the rapid identification of a number of compounds for which DNA binding properties were validated through demonstration of concentration-dependent DNA binding and increased thermal melting of A/T- or G/C-rich DNA sequences. Selected compounds were assayed further for cell proliferation inhibition in glioblastoma cells. Seven distinct compounds emerged from this screening procedure that represent structures unknown previously to be capable of targeting DNA leading to cell death. These agents may represent structures worthy of further modification to optimally explore their potential as cytotoxic anti-cancer agents. In addition, the general screening strategy described may find broader impact toward the rapid discovery of DNA targeted agents with biological activity.
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影响因子：
2.9
作者：
Glass, LaTeca S.;Nguyen, Binh;Georgiadis, Millie M.
通讯作者：
Georgiadis, Millie M.
从DNA结合分子库中发现异常基因转录的抑制剂：抑制LEF-1介导的基因转录和致癌转化。
影响因子：
15
作者：
Stover JS;Shi J;Jin W;Vogt PK;Boger DL
通讯作者：
Boger DL
影响因子：
3.5
作者：
Ismail, MA;Batista-Parra, A;Boykin, DW
通讯作者：
Boykin, DW
影响因子：
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作者：
Zhang, JH;Chung, TDY;Oldenburg, KR
通讯作者：
Oldenburg, KR
影响因子：
--
作者：
Dickinson, LA;Burnett, R;Gottesfeld, JM
通讯作者：
Gottesfeld, JM