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ID: ALA4732051
Journal: Eur J Med Chem
Title: The discovery of potent small molecule activators of human STING.
Authors: Pryde DC,Middya S,Banerjee M,Shrivastava R,Basu S,Ghosh R,Yadav DB,Surya A
Abstract: The adaptor protein STING plays a major role in innate immune sensing of cytosolic nucleic acids, by triggering a robust interferon response. Despite the importance of this protein as a potential therapeutic target for serious unmet medical conditions including cancer and infectious disease there remains a paucity of STING ligands. Starting with a benzothiazinone series of weak STING activators (human EC ∼10 μM) we identified several chemotypes with sub-micromolar STING activity across all the major protein polymorphs. An example compound 53 based on an oxindole core structure demonstrated robust on-target functional activation of STING (human EC 185 nM) in immortalised and primary cells and a cytokine induction fingerprint consistent with STING activation. Our study has identified several related series of potent small molecule human STING activators with potential to be developed as immunomodulatory therapeutics.
CiteXplore: 33038794