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.

  • COMMENT

Targeted protein degraders: a call for collective action to advance safety assessment

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Nature Reviews Drug Discovery 21, 401-402 (2022)

doi: https://doi.org/10.1038/d41573-022-00055-9

Acknowledgements

This work was supported by the Health and Environmental Science Institute (HESI). The authors gratefully acknowledge the contributions of all speakers and the input from workshop participants of all sectors and geographical areas for enriching the discussions.

References

  1. Chamberlain, P. P. & Hamann, L.G. Development of targeted protein degradation therapeutics. Nat. Chem. Biol. 15, 937–944 (2019).

    PubMed  Article  Google Scholar 

  2. Bekes, M., Langley, D. R. & Crews, C. M. PROTAC targeted protein degraders: the past is prologue. Nat. Rev. Drug Discov. 21, 181–200 (2022).

    PubMed  Article  Google Scholar 

  3. Moreau, K. et al. Proteolysis-targeting chimeras in drug development: a safety perspective. Br. J. Pharmacol. 177, 1709–1718 (2020).

    PubMed  Article  Google Scholar 

  4. Donovan, K. A. et al. Mapping the degradable kinome provides a resource for expedited degrader development. Cell 183, 1714–1731.e10 (2020).

    PubMed  Article  Google Scholar 

  5. Nowak, R. & Jones, L, H. Target validation using PROTACs: applying the four pillars framework. SLAS Discov. 26, 474–483 (2021).

    PubMed  Article  Google Scholar 

Download references

Supplementary Information

  1. Supplementary information

Competing Interests

HESI does not have a direct conflict of interest and holds no financial stake in specific pharmaceutical products or methods. The HESI scientific programming described in this article was supported by in-kind contributions from public and private sector participants of time, expertise and experimental effort, and direct funding from multiple pharmaceutical companies. A list of supporting organizations is available at www.hesiglobal.org. L.H.J. serves on the scientific advisory board for, and holds equity in, Interline Therapeutics, Umbra Therapeutics and Rapafusyn Pharmaceuticals. He also holds equity in Jnana Therapeutics and consults for EoCys. The Center for Protein Degradation at DFCI receives research funding from Deerfield. L.L., M.P., M.R, R.R., K.S., L.V. and M.B.W. are employed by companies engaged in the TPD field as indicated in their affiliations.

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

Quick links