TARGETED PROTEIN DEGRADATION

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

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

References

  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. https://doi.org/10.1038/s41589-019-0304-8 (2019).

  10. 10.

    Zhang, X. et al. Nat. Chem. Biol. https://doi.org/10.1038/s41589-019-0279-5 (2019).

Download references

Author information

Correspondence to Georg E. Winter.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark