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. 2022 Jun 3;17(11):e202100719.
doi: 10.1002/cmdc.202100719. Epub 2022 Mar 31.

Identification of Ziyuglycoside II from a Natural Products Library as a STING Agonist

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Identification of Ziyuglycoside II from a Natural Products Library as a STING Agonist

Xiangling Cui et al. ChemMedChem. .

Abstract

Given the emerging pivotal roles of stimulator of interferon genes (STING) in host pathogen defense and immune-oncology, STING is regarded as a promising target for drug development. Cyclic dinucleotides (CDNs) are the first-generation STING agonists. However, their poor metabolic stability and membrane permeability limits their therapeutic application. In contrast, small-molecule STING agonists show superior properties such as molecular weight, polar character, and delivery diversity. The quest for a potent small-molecular agonist of human STING remains ongoing. In our study, through an IRF/IFN pathway-targeted cell-based screen of a natural products library, we identified a small-molecular STING agonist, Ziyuglycoside II, termed ST12, with potent stimulation of the IRF/IFN and NF-κB pathways. Furthermore, its binding to the C-terminal domain of human STING, detected by bio-layer interferometry, indicates that ST12 is a human STING agonist. Further Tanimoto similarity analysis with existing small-molecule STING agonists indicates that ST12 is a lead compound with a novel core structure for the further optimization.

Keywords: STING; natural products; small-molecule STING agonist; ziyuglycoside II.

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References

    1. G. N. Barber, Nat. Rev. Immunol. 2015, 15, 760-770.
    1. None
    1. J. Ahn, H. Konno, G. N. Barber, Oncogene 2015, 34, 5302-5308;
    1. G. Berger, M. Marloye, S. E. Lawler, Trends Mol. Med. 2019, 25, 412-427;
    1. J. B. Foote, L. A. Emens, Immunotherapy 2018, 10, 729-731.

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