RU320521 是选择性的环状 GMP-AMP 合成酶 (cGAS) 抑制剂，抑制 cGAS 介导的干扰素上调。它也抑制dsDNA 激活受体的活性，IC50为 700 nM。它可降低来自 Aicardi-Goutières 综合征小鼠模型的巨噬细胞中干扰素的组成型表达。

RU.521 (RU320521) is a potent dsDNA inhibitor (IC50 : 700 nM), inhibition of the dsDNA pathway by RU.521 requires the presence of cGAS.

Treatment of primary BMDMs with RU.521 or its analogs reduced IFNB1 expression in mice, indicating their effectiveness in suppressing intrinsic DNA-dependent, constitutively-activated type I interferon expression in cells deficient of a cytoplasmic DNA exonuclease.

Small-molecule compounds were serially diluted to concentrations spanning the range tested in the response curves were added to 6.7?×?10^5 RAW-Blue macrophages plated 16?h prior in 96-well dishes, then harvested 72?h after compound addition. ATP was measured using CellTiter Glo Viability Assay using 50?μM Tamoxifen as a positive control for cytotoxicity. Viability values were generated using vehicle (DMSO) or the first dose as 100% and Tamoxifen as 0%. Outliers were removed.

the chronically elevated levels of cytokines observed in Trex1 null mice are a consequence of constitutively activated cGAS, due to the inability to eliminate aberrantly localized self-DNA. We harvested BMDMs from 6–8-week old Trex1 ?/? mice, treated them with each compound, and measured expression levels of IFNB1 by quantitative reverse transcription PCR (qRT-PCR). Treatment of primary BMDMs with RU.521 or its analogs reduced IFNB1 expression, indicating their effectiveness in suppressing intrinsic DNA-dependent, constitutively-activated type I interferon expression in cells deficient of a cytoplasmic DNA exonuclease.

2262452-06-0

C19H12Cl2N4O3

415.23

RU320521

DMSO:125 mg/mL (301.04 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years