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Addressing Compound Reactivity and Aggregation Assay Interferences: Case Studies of Biochemical High-Throughput Screening Campaigns Benefiting from the National Institutes of Health Assay Guidance Manual Guidelines

  1. Author:
    Coussens,Nathan [ORCID]
    Auld, Douglas S [ORCID]
    Thielman, Jonathan R [ORCID]
    Wagner, Bridget K
    Dahlin, Jayme L [ORCID]

  2. Author Address

    Molecular Pharmacology Laboratories, Division of Cancer Treatment and Diagnosis Laboratory Support, Applied/Developmental Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Novartis Institutes for Biomedical Research, Cambridge, MA, USA., Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA, USA., National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.,
    1. Year: 2021
    2. Date: Jul 03
    3. Epub Date: 2021 07 03
  2. Journal: SLAS discovery : advancing life sciences R & D
    1. Pages: 24725552211026239
  4. Type of Article: Article
  5. Article Number: 24725552211026239
  6. ISSN: 2472-5552
  1. Abstract:

    Compound-dependent assay interferences represent a continued burden in drug and chemical probe discovery. The open-source National Institutes of Health/National Center for Advancing Translational Sciences (NIH/NCATS) Assay Guidance Manual (AGM) established an "Assay Artifacts and Interferences" section to address different sources of artifacts and interferences in biological assays. In addition to the frequent introduction of new chapters in this important topic area, older chapters are periodically updated by experts from academia, industry, and government to include new technologies and practices. Section chapters describe many best practices for mitigating and identifying compound-dependent assay interferences. Using two previously reported biochemical high-throughput screening campaigns for small-molecule inhibitors of the epigenetic targets Rtt109 and NSD2, the authors review best practices and direct readers to high-yield resources in the AGM and elsewhere for the mitigation and identification of compound-dependent reactivity and aggregation assay interferences.

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External Sources

  1. View Full Text
  2. DOI: 10.1177/24725552211026239
  3. PMID: 34218710
  4. View record in Web of Science®
  5. WOS: 000674723200001

Library Notes

  1. Fiscal Year: FY2020-2021
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