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ChemMedChem

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

Published:15 March 2022 DOI: 10.1002/cmdc.202100719 PMID: 35293138
Xiangling Cui, Yongli Xie, Min Zhang, Jieke Gao, Xujun Zhou, Dr. Jiwei Ding, Dr. Shan Cen, Dr. Jinming Zhou

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.

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Procduct Name CAS Molecular Formula Supplier Price
Ziyuglycoside II 35286-59-0 C35H56O8 181 suppliers Inquiry

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