@article{APS11477,
author = {Man Zhao and Zu-yi Jin and Wei-zhen Fan and Peng-fei Qiang and Zhi-hua Zheng and Guo-feng Li and Liang Hong and Min Li},
title = {Zinc pyrithione functions as a small-molecule STING agonist to exert antitumor immunotherapy effects},
journal = {Acta Pharmacologica Sinica},
volume = {47},
number = {3},
year = {2026},
keywords = {},
abstract = {The stimulator of interferon genes (STING) is a crucial pattern recognition receptor that activates innate immunity, particularly in response to pathogen infection and various stimuli. Notably, activation of STING exhibits remarkable potential in enhancing anti-tumor immunity, underscoring the significance of discovering STING small molecule agonists. Recently, zinc pyrithione (ZPT), a marketed antifungal small molecule, has been reported to possess anti-tumor activity through various mechanisms. Our preliminary screening of STING agonists revealed that ZPT could significantly induce STING activation. In this study, we investigated whether ZPT exerted anticancer effects as a small molecule activator of STING. We showed that ZPT bound to the STING protein in vitro with KD value of 2.72 μM, and ZPT (1–16 μM) dose-dependently activated the STING-TBK1-IRF3 signaling axis in THP-1 cells. In MC38 tumor-bearing wild-type C57BL/6 mice with normal immune systems, administration of ZPT (5, 10, or 20 mg/kg, i.p., every two days for 14 days) dose-dependently inhibited the tumor growth, activated CD45+, CD3+, and CD8+ T cells in both tumors and spleens, and significantly elevated IL-6 secretion in the peripheral blood. These results highlight the potential of ZPT as an immunotherapeutic agent targeting STING.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/11477}
}