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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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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DOI: https://doi.org/10.1038/s41589-024-01557-w