RU32052;RU320521;10mM in DMSO;RU.521 RU320521;RU320521 RU-320521;RU.521, 10 mM in DMSO;RU.521;RU521;RU-320521;1(3H)-Isobenzofuranone, 3-[1-(6,7-dichloro-1H-benzimidazol-2-yl)-5-hydroxy-3-methyl-1H-pyrazol-4-yl]-;3-(1-(6,7-dichloro-1H-benzo[d]imidazol-2-yl)-5-hydroxy-3-methyl-1H-pyrazol-4-yl)isobenzofuran-1(3H)-one;inflammatory,oxidative stress,RU 320521,cGAS,RU-320521,Inhibitor,inhibit,RU.521,Cyclic GMP-AMP Synthase,signaling pathway
In sequence, RU.521 were diluted in the solution containing 10% DMSO, 40% PEG300, 5% Tween-80% and 45% saline. Then, the solution was sonicated until there was no obvious precipitation. The method of administration and the effectiveness of RU.521 was described in previous studies. In brief, mice were intraperitoneally injected with 100 μL solution with or without RU.521 at a 5 mg/kg dose for 3 consecutive days. The intraperitoneal injection was performed within 1 h after the initial intratracheal injection of ZnONPs.
Biochem/physiol Actions
The potency and selectivity of a chemically improved inhibitor, RU.521, in cellular assays show that while it inhibits cGAS-mediated interferon upregulation, it has reduced to no effect on inflammatory pathways independent of cGAS. Furthermore, RU.521 suppresses the chronically elevated levels of type I interferon observed in primary macrophages from Trex1 null mice, a model of AGS. Crystal structures show that RU.521 occupies the catalytic pocket of murine cGAS, thus interfering with the entry of its ATP and GTP substrates. RU.521 inhibits cytoplasmic DNA-dependent upregulation of IRF3-dependent transcriptional targets only in the presence of an intact cGAS-STING pathway[1-2].
