XL-3158 is a selective and cross-species Cyclic GMP-AMP synthase (cGAS) inhibitor. It simultaneously occupies allosteric and orthosteric sites, stabilizing the activation loop in a closed, inactive conformation, thereby attenuating cGAS-DNA interactions. It efficiently penetrates cells by inhibiting aggregate formation, effectively reducing the local concentration of cGAS within cells. This compound can be used for the study of cGAS-dependent inflammatory diseases.
- Blocks cGAS intracellular condensation with DNA by inhibiting cGAS phase separation in L929 cells.
- Specifically inhibits downstream signaling activation of the cGAS-STING pathway in THP-1 Dual cells.
- Selectively inhibits the DNA-triggered cGAS-dependent interferon pathway in THP-1 Dual cells.
- Has CC50 values of 77.55 μM against THP-1 cells and 56.79 μM against RAW-ISG cells.
- Attenuates Cerulein-induced acute pancreatitis.