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COVALENT PRODRUGS

A masked zinger to block GPX4

Nature Chemical Biology volume 16, pages 482–483 (2020)Cite this article

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Ferroptosis induced by GPX4 inhibition offers promise for killing drug-resistant cancer cells, yet current GPX4 inhibitors lack selectivity. The discovery of masked nitrile oxide electrophiles as selective prodrug inhibitors of GPX4 points to an attractive path for chemically inducing ferroptosis.

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Fig. 1: Electrophile unmasking in cells leads to GPX4 inhibition and ferroptosis.

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Acknowledgements

The authors thank the NIH (CA231991, CA228436) for support.

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Authors and Affiliations

  1. Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA

    Stefan G. Kathman & Benjamin F. Cravatt

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  1. Stefan G. Kathman
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  2. Benjamin F. Cravatt
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Correspondence to Stefan G. Kathman or Benjamin F. Cravatt.

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Kathman, S.G., Cravatt, B.F. A masked zinger to block GPX4. Nat Chem Biol 16, 482–483 (2020). https://doi.org/10.1038/s41589-020-0511-3

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