ChX710

Cell lines

HEK-293T (human embryonic kidney epithelial cells), A549 (human lung epithelial adenocarcinoma cells), MRC5 (human lung fibroblasts), Vero (African green monkey kidney epithelial cells), and primary human peripheral blood mononuclear cells (PBMCs)

Preparation Method

Reporter cell lines (e.g., STING-37, a HEK-293 cell line stably expressing luciferase under the control of ISRE) or other cell types were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal calf serum (FCS), penicillin, and streptomycin at 37°C and 5% CO₂. Cells were treated with ChX710 (6-50µM) or related compounds for specified durations. For synergy experiments, cells were co-treated with ChX710 and transfected with plasmid DNA or stimulated with 2',3'-cGAMP using JetPrime transfection reagent.

Reaction Conditions

6-50µM; 8-48 hours.

Applications

ChX710 specifically activates the Interferon-Stimulated Response Element (ISRE) promoter. This activation is dependent on the adaptor protein MAVS and the transcription factor IRF1, but independent of STAT1/STAT2. ChX710 induces phosphorylation of IRF3 but is insufficient to trigger type I interferon (IFN-α/β) secretion on its own. ChX710 induces a modest, cell-type-specific profile of Interferon-Stimulated Genes (ISGs). Crucially, ChX710 potently primes and synergistically enhances the cellular type I interferon response to cytosolic (transfected) DNA, leading to a strong, STING-dependent increase in IFN-β secretion and ISG expression. ChX710 exhibits significant cytotoxicity at higher concentrations, reducing cellular ATP levels and viability.

References:
[1] Khiar S, Lucas-Hourani M, Nisole S, et al. Identification of a small molecule that primes the type I interferon response to cytosolic DNA. Sci Rep. 2017 May 31;7(1):2561.