An in vitro Fo''rster resonance energy transfer-based high-throughput screening assay identifies inhibitors of SUMOylation E2 Ubc9
文献类型：期刊论文
| 作者 | Wang, Yu-zhe3,4,5; Liu, Xiao1; Way, George6; Madarha, Vipul6; Zhou, Qing-tong2; Yang, De-hua3,4 ; Liao, Jia-yu6; Wang, Ming-wei1,3,4,5
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2020-04-27 |
| 页码 | 10 |
| ISSN号 | 1671-4083 |
| 关键词 | SUMOylation inhibitor WNN0605-F008 high-throughput screening Ubc9 PIAS1 Fo''rster resonance energy transfer surface plasmon resonance |
| DOI | 10.1038/s41401-020-0405-7 |
| 通讯作者 | Yang, De-hua(dhyang@simm.ac.cn) ; Liao, Jia-yu(jliao@engr.ucr.edu) ; Wang, Ming-wei(mwwang@simm.ac.cn) |
| 英文摘要 | SUMOylation is one of the posttranslational modifications that mediate cellular activities such as transcription, DNA repair, and signal transduction and is involved in the cell cycle. However, only a limited number of small molecule inhibitors have been identified to study its role in cellular processes. Here, we report a Fo''rster resonance energy transfer (FRET) high-throughput screening assay based on the interaction between E2 Ubc9 and E3 PIAS1. Of the 3200 compounds screened, 34 (1.1%) showed higher than 50% inhibition and 4 displayed dose-response inhibitory effects. By combining this method with a label-free surface plasmon resonance (SPR) assay, false positives were excluded leading to discovering WNN0605-F008 and WNN1062-D002 that bound to Ubc9 with K-D values of 1.93 +/- 0.62 and 5.24 +/- 3.73 mu M, respectively. We examined the effect of the two compounds on SUMO2-mediated SUMOylation of RanGAP1, only WNN0605-F008 significantly inhibited RanGAP1 SUMOylation, whereas WNN1062-D002 did not show any inhibition. These compounds, with novel chemical scaffolds, may serve as the initial material for developing new SUMOylation inhibitors. |
| WOS关键词 | PROTEIN SUMOYLATION ; CONJUGATING ENZYME ; SUMO ; UBIQUITIN ; PIAS1 ; ACTIVATION ; EXPRESSION ; RANGAP1 ; BINDING |
| 资助项目 | National Natural Science Foundation of China[81872915] ; National Natural Science Foundation of China[81573479] ; National Natural Science Foundation of China[81773792] ; National Natural Science Foundation of China[21704064] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program[2018ZX09735-001] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program[2018ZX09711002-002-005] ; National Key R&D Program of China[2018YFA0507000] ; Novo Nordisk-CAS Research Fund[NNCAS-2017-1-CC] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000528979400002 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/280478]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Yang, De-hua; Liao, Jia-yu; Wang, Ming-wei |
| 作者单位 | 1.Fudan Univ, Shanghai Med Coll, Shanghai 200032, Peoples R China 2.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.Univ Calif Riverside, Bourns Coll Engn, Dept Bioengn, Riverside, CA 92521 USA |
| 推荐引用方式 GB/T 7714 | Wang, Yu-zhe,Liu, Xiao,Way, George,et al. An in vitro Fo''rster resonance energy transfer-based high-throughput screening assay identifies inhibitors of SUMOylation E2 Ubc9[J]. ACTA PHARMACOLOGICA SINICA,2020:10. |
| APA | Wang, Yu-zhe.,Liu, Xiao.,Way, George.,Madarha, Vipul.,Zhou, Qing-tong.,...&Wang, Ming-wei.(2020).An in vitro Fo''rster resonance energy transfer-based high-throughput screening assay identifies inhibitors of SUMOylation E2 Ubc9.ACTA PHARMACOLOGICA SINICA,10. |
| MLA | Wang, Yu-zhe,et al."An in vitro Fo''rster resonance energy transfer-based high-throughput screening assay identifies inhibitors of SUMOylation E2 Ubc9".ACTA PHARMACOLOGICA SINICA (2020):10. |
入库方式： OAI收割
来源：上海药物研究所
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