RU.521 is an inhibitor of cyclic GMP-AMP synthase (cGAS), an important innate immune system sensor of foreign cytoplasmic double-stranded DNA.1,2 IC50 = 0.70 µM in dsDNA-stimulated RAW macrophages1 and ~0.80 µM in wild type human THP-1 cells2. It is selective for cGAS with no targeting of IFNB1 protein, interferon receptors, or downstream signaling components of the JAK/STAT pathway. RU.521 was able to significantly increase cardiac output in a mouse model of sepsis.3 Active in both mouse and human cell lines.
- Vincent et al. (2017), Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice; Nat. Commun. 8 750
- Wiser et al. (2020), Small molecule inhibition of human cGAS reduces total cGAMP output and cytokine expression in cells; Sci. Rep. 10 7604
- Xu et al. (2020), Small molecule inhibition of cyclic GMP-AMP synthase ameliorates sepsis-induced cardiac dysfunction in mice; Life Sci. 260 118315