2. Academic Validation
  3. Zinc pyrithione functions as a small-molecule STING agonist to exert antitumor immunotherapy effects

Zinc pyrithione functions as a small-molecule STING agonist to exert antitumor immunotherapy effects

  • Acta Pharmacol Sin. 2025 Oct 17. doi: 10.1038/s41401-025-01674-9.
Man Zhao # 1 2,  Zu-Yi Jin # 1,  Wei-Zhen Fan # 1,  Peng-Fei Qiang 1,  Zhi-Hua Zheng 1,  Guo-Feng Li 3,  Liang Hong 4,  Min Li 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Anti-infective Drug Discovery and Development, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
  • 2 School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518060, China.
  • 3 School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518060, China. liguofeng@szu.edu.cn.
  • 4 State Key Laboratory of Anti-infective Drug Discovery and Development, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China. hongliang@sysu.edu.cn.
  • 5 State Key Laboratory of Anti-infective Drug Discovery and Development, Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China. limin65@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 41107405 DOI: 10.1038/s41401-025-01674-9
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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z