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Characterization of Specific N-a-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library

  1. Author:
    Kung, Pei-Pei
    Bingham, Patrick
    Burke, Benjamin J
    Chen, Qiuxia
    Cheng, Xuemin
    Deng, Ya-Li
    Dou, Dengfeng
    Feng, Junli
    Gallego, Gary M
    Gehring, Michael R
    Grant, Stephan K
    Greasley, Samantha
    Harris, Anthony R
    Maegley, Karen A
    Meier,Jordan
    Meng, Xiaoyun
    Montano,Jose
    Morgan, Barry A
    Naughton, Brigitte S
    Palde, Prakash B
    Paul, Thomas A
    Richardson, Paul
    Sakata, Sylvie
    Shaginian, Alex
    Sonnenburg, William K
    Subramanyam, Chakrapani
    Timofeevski, Sergei
    Wan, Jinqiao
    Yan, Wen
    Stewart, Albert E

  2. Author Address

    Worldwide Research and Development, Pfizer Inc., 10770 Science Center Drive, San Diego, California 92121, United States., HitGen Inc., Building 6, No.8, Huigu first East Road, Tianfu International Bio-Town, Shuangliu District, Chengdu, Sichuan 610200, P.R. China., Chemical Biology Laboratory, National Cancer Institute, Frederick, Maryland 21702, United States., HitGen Pharmaceuticals Inc., PO Box 88240, Houston, Texas 77288, United States.,
    1. Year: 2020
    2. Date: Jun 11
    3. Epub Date: 2020 04 10
  2. Journal: ACS medicinal chemistry letters
    1. 11
    2. 6
    3. Pages: 1175-1184
  4. Type of Article: Article
  5. ISSN: 1948-5875
  1. Abstract:

    Two novel compounds were identified as Naa50 binders/inhibitors using DNA-encoded technology screening. Biophysical and biochemical data as well as cocrystal structures were obtained for both compounds (3a and 4a) to understand their mechanism of action. These data were also used to rationalize the binding affinity differences observed between the two compounds and a MLGP peptide-containing substrate. Cellular target engagement experiments further confirm the Naa50 binding of 4a and demonstrate its selectivity toward related enzymes (Naa10 and Naa60). Additional analogs of inhibitor 4a were also evaluated to study the binding mode observed in the cocrystal structures. Copyright © 2020 American Chemical Society.

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External Sources

  1. View Full Text
  2. DOI: 10.1021/acsmedchemlett.0c00029
  3. PMID: 32550998
  4. PMCID: PMC7294708
  5. View record in Web of Science®
  6. WOS: 000541747800019

Library Notes

  1. Fiscal Year: FY2019-2020
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