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Targeting epigenetic protein-protein interactions with small-molecule inhibitors. | LitMetric

AI Article Synopsis

  • - Epigenetic protein-protein interactions (PPIs) are crucial for regulating gene expression, and disruptions in these interactions can lead to various diseases.
  • - Researchers are focusing on developing small-molecule inhibitors to target these PPIs, particularly in the context of cancer therapy, with some success in targeting known domains.
  • - The article suggests that creating effective inhibitors for challenging epigenetic PPIs, especially those recognizing methylated lysine on histones, may require interdisciplinary strategies and a broad exploration of chemical compounds.

Article Abstract

Epigenetic protein-protein interactions (PPIs) play essential roles in regulating gene expression, and their dysregulations have been implicated in many diseases. These PPIs are comprised of reader domains recognizing post-translational modifications on histone proteins, and of scaffolding proteins that maintain integrities of epigenetic complexes. Targeting PPIs have become focuses for development of small-molecule inhibitors and anticancer therapeutics. Here we summarize efforts to develop small-molecule inhibitors targeting common epigenetic PPI domains. Potent small molecules have been reported for many domains, yet small domains that recognize methylated lysine side chains on histones are challenging in inhibitor development. We posit that the development of potent inhibitors for difficult-to-prosecute epigenetic PPIs may be achieved by interdisciplinary approaches and extensive explorations of chemical space.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7421387PMC
http://dx.doi.org/10.4155/fmc-2020-0082DOI Listing

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