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DOI | 10.1038/s41467-018-03996-1 |
Assay interference and off-target liabilities of reported histone acetyltransferase inhibitors | |
Dahlin, Jayme L.1; Nelson, Kathryn M.2; Strasser, Jessica M.2; Barsyte-Lovejoy, Dalia3; Szewczyk, Magdalena M.3; Organ, Shawna3; Cuellar, Matthew2; Singh, Gurpreet2; Shrimp, Jonathan H.4; Nguyen, Nghi5; Meier, Jordan L.4; Arrowsmith, Cheryl H.3; Brown, Peter J.3; Baell, Jonathan B.3,5,6; Walters, Michael A.2 | |
2017-11-15 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Canada; Australia; Peoples R China |
英文摘要 | Many compounds with potentially reactive chemical motifs and poor physicochemical properties are published as selective modulators of biomolecules without sufficient validation and then propagated in the scientific literature as useful chemical probes. Several histone acetyltransferase (HAT) inhibitors with these liabilities are now routinely used to probe epigenetic pathways. We profile the most commonly used HAT inhibitors and confirm that the majority of them are nonselective interference compounds. Most (15 out of 23, 65%) of the inhibitors are flagged by ALARM NMR, an industry-developed counter-screen for promiscuous compounds. Biochemical counter-screens confirm that most of these compounds are either thiol-reactive or aggregators. Selectivity panels show many of these compounds modulate unrelated targets in vitro, while several also demonstrate nonspecific effects in cell assays. These data demonstrate the usefulness of performing counter-screens for bioassay promiscuity and assay interference, and raise caution about the utility of many widely used, but insufficiently validated, compounds employed in chemical biology. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000415262500015 |
WOS关键词 | SMALL-MOLECULE MODULATORS ; HIGH-THROUGHPUT ; PAINS ; DISCOVERY ; P300 ; AGGREGATION ; SCREENS ; POTENT ; HITS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203769 |
专题 | 资源环境科学 |
作者单位 | 1.Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA; 2.Univ Minnesota, Inst Therapeut Discovery & Dev, Minneapolis, MN 55414 USA; 3.Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada; 4.NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA; 5.Monash Univ, Monash Inst Pharmaceut Sci, Med Chem Theme, Parkville, Vic 3052, Australia; 6.Nanjing Tech Univ, Sch Pharmaceut Sci, Nanjing 211816, Jiangsu, Peoples R China |
推荐引用方式 GB/T 7714 | Dahlin, Jayme L.,Nelson, Kathryn M.,Strasser, Jessica M.,et al. Assay interference and off-target liabilities of reported histone acetyltransferase inhibitors[J]. NATURE COMMUNICATIONS,2017,8. |
APA | Dahlin, Jayme L..,Nelson, Kathryn M..,Strasser, Jessica M..,Barsyte-Lovejoy, Dalia.,Szewczyk, Magdalena M..,...&Walters, Michael A..(2017).Assay interference and off-target liabilities of reported histone acetyltransferase inhibitors.NATURE COMMUNICATIONS,8. |
MLA | Dahlin, Jayme L.,et al."Assay interference and off-target liabilities of reported histone acetyltransferase inhibitors".NATURE COMMUNICATIONS 8(2017). |
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