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Drug discovery

The druggability of SH2 domains unmasked

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Developing inhibitors for SH2 domains is challenging due to their shallow pockets and highly charged ligands. Structure-guided drug design has enabled the discovery of a cell-permeable covalent inhibitor of the SOCS2 SH2 domain, a key regulator of cytokine signaling pathways.

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Fig. 1: Development of a cell-permeable ligand targeting the SH2 domain of the cytokine receptor signaling regulator SOCS2.

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  1. Institute of Physiological Chemistry, Philipps-University of Marburg, Marburg, Germany

    Oliver Hantschel

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  1. Oliver Hantschel
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Correspondence to Oliver Hantschel.

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Hantschel, O. The druggability of SH2 domains unmasked. Nat Chem Biol 20, 271–272 (2024). https://doi.org/10.1038/s41589-024-01557-w

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