Skip to main content

Thank you for visiting 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.


Aiming for the pocket

Isoform-selective inhibition of JAK kinases is of key interest in drug discovery. A novel pocket in the JAK pseudokinase domain was targeted by an allosteric covalent inhibitor, leading to specific JAK1 inhibition and providing a deeper understanding of cytokine signaling.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: JAK1 inhibition by VVD-118313.


  1. Schwartz, D. M. et al. Nat. Rev. Drug Discov. 17, 78 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Spinelli, F. R., Meylan, F., O’Shea, J. J. & Gadina, M. Eur. J. Immunol. 51, 1615–1627 (2021).

    Article  CAS  PubMed  Google Scholar 

  3. Kavanagh, M. E. et al. Nat. Chem. Biol. (2022).

  4. Hammarén, H. M., Virtanen, A. T., Raivola, J. & Silvennoinen, O. Cytokine 118, 48–63 (2019).

    Article  PubMed  Google Scholar 

  5. Vinogradova, E. V. et al. Cell 182, 1009–1026.e29 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wylie, A. A. et al. Nature 543, 733–737 (2017).

    Article  CAS  PubMed  Google Scholar 

  7. Glassman, C. R. et al. Science 376, 163–169 (2022).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Olli Silvennoinen.

Ethics declarations

Competing interests

O.S. holds intellectual property rights to JAK kinases, is a scientific advisory board member and co-founder of Ajax Therapeutics and has received speaking honoraria from Pfizer and Abbvie.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Silvennoinen, O., Haikarainen, T. & Virtanen, A. Aiming for the pocket. Nat Chem Biol 18, 1296–1297 (2022).

Download citation

  • Published:

  • Issue Date:

  • DOI:


Quick links

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