Assay interference and off-target liabilities of reported histone acetyltransferase inhibitors

Jayme L. Dahlin; Kathryn M. Nelson; Jessica M. Strasser; Dalia Barsyte-Lovejoy; Magdalena M. Szewczyk; Shawna Organ; Matthew Cuellar; Gurpreet Singh; Jonathan H. Shrimp; Nghi Nguyen; Jordan L. Meier; Cheryl H. Arrowsmith; Peter J. Brown; Jonathan B. Baell; Michael A. Walters

doi:10.1038/s41467-017-01657-3

Nature Communications (Nov 2017)

Assay interference and off-target liabilities of reported histone acetyltransferase inhibitors

Jayme L. Dahlin,
Kathryn M. Nelson,
Jessica M. Strasser,
Dalia Barsyte-Lovejoy,
Magdalena M. Szewczyk,
Shawna Organ,
Matthew Cuellar,
Gurpreet Singh,
Jonathan H. Shrimp,
Nghi Nguyen,
Jordan L. Meier,
Cheryl H. Arrowsmith,
Peter J. Brown,
Jonathan B. Baell,
Michael A. Walters

Affiliations

Jayme L. Dahlin: Department of Pathology, Brigham and Women’s Hospital
Kathryn M. Nelson: Institute for Therapeutics Discovery and Development, University of Minnesota
Jessica M. Strasser: Institute for Therapeutics Discovery and Development, University of Minnesota
Dalia Barsyte-Lovejoy: Structural Genomics Consortium, University of Toronto
Magdalena M. Szewczyk: Structural Genomics Consortium, University of Toronto
Shawna Organ: Structural Genomics Consortium, University of Toronto
Matthew Cuellar: Institute for Therapeutics Discovery and Development, University of Minnesota
Gurpreet Singh: Institute for Therapeutics Discovery and Development, University of Minnesota
Jonathan H. Shrimp: Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Nghi Nguyen: Medicinal Chemistry Theme, Monash Institute of Pharmaceutical Sciences, Monash University
Jordan L. Meier: Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Cheryl H. Arrowsmith: Structural Genomics Consortium, University of Toronto
Peter J. Brown: Structural Genomics Consortium, University of Toronto
Jonathan B. Baell: Medicinal Chemistry Theme, Monash Institute of Pharmaceutical Sciences, Monash University
Michael A. Walters: Institute for Therapeutics Discovery and Development, University of Minnesota

DOI: https://doi.org/10.1038/s41467-017-01657-3
Journal volume & issue: Vol. 8, no. 1
pp. 1 – 14

Abstract

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A substantial obstacle in basic research is the use of poorly validated tool compounds with purported useful biological functions. Here, the authors systematically profile widely used histone acetyltransferase inhibitors and find that the majority are nonselective interference compounds.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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