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Gao C, Margolis BJ, Strelow JM, et al. Beyond PAINs: Chemotype Sensitivity of Protein Methyltransferases in Screens. ACS Med Chem Lett. 2015;7(2):156-61doi: 10.1021/acsmedchemlett.5b00375.
Gao, C., Margolis, B. J., Strelow, J. M., Vidler, L. R., & Mader, M. M. (2016). Beyond PAINs: Chemotype Sensitivity of Protein Methyltransferases in Screens. ACS medicinal chemistry letters, 7(2), 156-61. https://doi.org/10.1021/acsmedchemlett.5b00375
Gao, Cen, et al. "Beyond PAINs: Chemotype Sensitivity of Protein Methyltransferases in Screens." ACS medicinal chemistry letters vol. 7,2 (2016): 156-61. doi: https://doi.org/10.1021/acsmedchemlett.5b00375
Gao C, Margolis BJ, Strelow JM, Vidler LR, Mader MM. Beyond PAINs: Chemotype Sensitivity of Protein Methyltransferases in Screens. ACS Med Chem Lett. 2015 Nov 19;7(2):156-61. doi: 10.1021/acsmedchemlett.5b00375. eCollection 2016 Feb 11. PMID: 26985291; PMCID: PMC4753540.
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ACS Med Chem Lett. 2015 Nov 19;7(2):156-61. doi: 10.1021/acsmedchemlett.5b00375. eCollection 2016 Feb 11.

Beyond PAINs: Chemotype Sensitivity of Protein Methyltransferases in Screens.

ACS medicinal chemistry letters

Cen Gao, Brandon J Margolis, John M Strelow, Lewis R Vidler, Mary M Mader

Affiliations

  1. Lilly Research Laboratories, Eli Lilly and Company , Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
  2. Research and Development, Eli Lilly and Company Ltd. , Sunninghill Road, Windlesham, Surrey GU20 6PH, United Kingdom.

PMID: 26985291 PMCID: PMC4753540 DOI: 10.1021/acsmedchemlett.5b00375

Abstract

Screening of the relatively new target class, the lysine and arginine methyltransferases (MTases), presents unique challenges in the identification and confirmation of active chemical matter. Examination of high throughput screening data generated using Scintillation Proximity Assay (SPA) format for a number of protein MTase targets reveals sensitivity to both the known pan assay interference compounds (PAINS) and also other scaffolds not currently precedented as assay interferers. We find that, in general, true actives show significant selectivity within the MTase family. With the exception of slight modifications of SAM-like compounds, scaffolds that are observed frequently in multiple MTase assays should be viewed with caution and should be carefully validated before following up.

Keywords: HTS; Methyltransferase; PAINS; epigenetics; promiscuity

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