Identification of a Selective RelA Inhibitor Based on DSE-FRET Screening Methods.
Identification of a Selective RelA Inhibitor Based on DSE-FRET Screening Methods.
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DOI：
10.3390/ijms21239150
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发表时间：
2020-11-30
影响因子：
5.6
通讯作者：
Tahara H
中科院分区：
文献类型：
--
作者：
Shiroma Y;Fujita G;Yamamoto T;Takahashi RU;Kumar A;Zhang KYJ;Ito A;Osada H;Yoshida M;Tahara H
Nuclear factor-κB (NF-κB) is an important transcription factor involved in various biological functions, including tumorigenesis. Hence, NF-κB has attracted attention as a target factor for cancer treatment, leading to the development of several inhibitors. However, existing NF-κB inhibitors do not discriminate between its subunits, namely, RelA, RelB, cRel, p50, and p52. Conventional methods used to evaluate interactions between transcription factors and DNA, such as electrophoretic mobility shift assay and luciferase assays, are unsuitable for high-throughput screening (HTS) and cannot distinguish NF-κB subunits. We developed a HTS method named DNA strand exchange fluorescence resonance energy transfer (DSE-FRET). This assay is suitable for HTS and can discriminate a NF-κB subunit. Using DSE-FRET, we searched for RelA-specific inhibitors and verified RelA inhibition for 32,955 compounds. The compound A55 (2-(3-carbamoyl-6-hydroxy-4-methyl-2-oxopyridin-1(2H)-yl) acetic acid) selectively inhibited RelA–DNA binding. We propose that A55 is a seed compound for RelA-specific inhibition and could be used in clinical applications.
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DOI：
10.1016/j.ymeth.2014.07.007
发表时间：
2015-01
期刊：
Methods (San Diego, Calif.)
影响因子：
--
作者：
Kumar A;Zhang KY
通讯作者：
Zhang KY
影响因子：
7.8
作者：
Koehler, Angela N.
通讯作者：
Koehler, Angela N.
影响因子：
5.6
作者：
Halgren, Thomas A.
通讯作者：
Halgren, Thomas A.
影响因子：
5.6
作者：
Hawkins, Paul C. D.;Nicholls, Anthony
通讯作者：
Nicholls, Anthony
影响因子：
56.9
作者：
KOPP, E;GHOSH, S
通讯作者：
GHOSH, S