STING activation by teniposide: a potential direct mechanism beyond cGAS stimulation.

ABSTRACT:

Introduction

The STimulator of Interferon Genes (STING) is a key adaptor protein in the innate immune response to cytosolic DNA, making it a promising therapeutic target. Identifying novel STING ligands could provide new opportunities for immune modulation.

Methods

We employed high-throughput virtual screening to identify potential STING ligands and selected Teniposide, an anticancer drug primarily used for infant leukemia. Direct binding of Teniposide to STING's cytosolic domain was confirmed via isothermal titration calorimetry (ITC) and validated using a double mutant STING variant unable to bind Teniposide. Computational docking and molecular dynamics simulations were performed to characterize the binding mode.

Results

Teniposide activated the IFN-β signaling path

SUBMITTER: Arranz-Herrero J 

PROVIDER: S-EPMC12808447 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature