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KINASE INHIBITORS

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.

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Fig. 1: JAK1 inhibition by VVD-118313.

References

  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. https://doi.org/10.1038/s41589-022-01098-0 (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

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Correspondence to Olli Silvennoinen.

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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.

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Silvennoinen, O., Haikarainen, T. & Virtanen, A. Aiming for the pocket. Nat Chem Biol 18, 1296–1297 (2022). https://doi.org/10.1038/s41589-022-01120-5

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  • DOI: https://doi.org/10.1038/s41589-022-01120-5

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