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Targeting non-bromodomain chromatin readers

Nature Structural & Molecular Biology volume 26, pages 863–869 (2019)Cite this article

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Abstract

Chromatin regulatory proteins are increasingly recognized as potential new drug targets. Many of these proteins harbor one or more so called ‘reader domains’ that recognize covalent modifications of lysine and arginine residues, typically on histones, which mediate specific interactions within chromatin. Here we review recent progress in the discovery of drug-like small molecules that antagonize the function of methyl-lysine and methyl-arginine reader domains (Royal family, plant homeodomain (PHD) and WD40 domains) as well as the acyl-lysine-binding YEATS domain.

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Fig. 1: MBT, chromodomain and Tudor domain antagonists.
Fig. 2: PWWP, PHD and YEATS domain ligands.
Fig. 3: WDR domain antagonists.

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Authors and Affiliations

  1. Structural Genomics Consortium, University of Toronto, Toronto, Canada

    Cheryl H. Arrowsmith & Matthieu Schapira

  2. Department of Medical Biophysics, University of Toronto, Toronto, Canada

    Cheryl H. Arrowsmith

  3. Princess Margaret Cancer Centre, Toronto, Canada

    Cheryl H. Arrowsmith

  4. Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada

    Matthieu Schapira

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Correspondence to Cheryl H. Arrowsmith.

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Arrowsmith, C.H., Schapira, M. Targeting non-bromodomain chromatin readers. Nat Struct Mol Biol 26, 863–869 (2019). https://doi.org/10.1038/s41594-019-0290-2

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