Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • RESEARCH HIGHLIGHT

Novel chemistry for covalent inhibitors

  1. Megan Cully
    View author publications

    You can also search for this author in PubMed  Google Scholar

The formation of an irreversible covalent bond between inhibitor and target increases the stability of the complex and can have therapeutic advantages such as longer duration of action. However, the exploration of covalent inhibitors has been limited by concerns about off-target reactivity, which may be alleviated by developing irreversible inhibitors based on weak electrophiles that only form covalent bonds after specific binding to a target protein. So far, most such inhibitors have incorporated acrylamides that form thioethers with cysteine residues in the target protein, but two new papers use different chemistry, and one targets residues other than cysteine.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Nature Reviews Drug Discovery 19, 754 (2020)

doi: https://doi.org/10.1038/d41573-020-00161-6

References

  1. Huang, H. et al. Covalent inhibition of NSD1 histone methyltransferase. Nat. Chem. Biol. https://doi.org/10.1038/s41589-020-0626-6 (2020)

  2. Brighty, G.J. et al. Using sulfuramidimidoyl fluorides that undergo sulfur(vi) fluoride exchange for inverse drug discovery. Nat. Chem. https://doi.org/10.1038/s41557-020-0530-4 (2020)

Download references

Subjects

Latest on:

Nature Careers

Jobs

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing

Search

Advanced search

Quick links