Stick it to E3s

The limited availability of small-molecule ligands for E3 ubiquitin ligases stymies the development of next-generation degraders. Two recent papers report the identification of novel, covalent and PROTAC-compatible ligands that hijack the previously untargeted ligases RNF114 and DCAF16.

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Fig. 1: Out of around 600 E3 ligases, only a small subset is amenable for targeted protein degradation.


  1. 1.

    Sakamoto, K. M. et al. Proc. Natl. Acad. Sci. USA 98, 8554–8559 (2001).

  2. 2.

    Paiva, S. L. & Crews, C. M. Curr. Opin. Chem. Biol. 50, 111–119 (2019).

  3. 3.

    Buckley, D. L. et al. J. Am. Chem. Soc. 134, 4465–4468 (2012).

  4. 4.

    Vassilev, L. T. et al. Science 303, 844–848 (2004).

  5. 5.

    Ito, T. et al. Science 327, 1345–1350 (2010).

  6. 6.

    Winter, G. E. et al. Science 348, 1376–1381 (2015).

  7. 7.

    Lu, J. et al. Chem. Biol. 22, 755–763 (2015).

  8. 8.

    Winter, G. E. et al. Mol. Cell 67, 5–18.e19 (2017).

  9. 9.

    Spradlin, J. N. et al. Nat. Chem. Biol. (2019).

  10. 10.

    Zhang, X. et al. Nat. Chem. Biol. (2019).

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Correspondence to Georg E. Winter.

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