| Name | RU.521 |
| Description | RU.521 (RU3205217) is a selective cyclic GMP-AMP synthetase (cGAS) inhibitor (mouse: IC50=0.11 μM), (human: IC50=2.94 μM). RU.521 is an inhibitor of the receptor activated by dsDNA (IC50=700 nM). RU.521 inhibits cGAS-mediated interferon upregulation. RU.521 reduces constitutive interferon expression in macrophages derived from a mouse model of Aicardi-Goutieres syndrome. |
| Cell Research | 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. |
| Animal Research | 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. |
| In vitro | METHODS: Human THP1-Dual cells were treated with RU.521 for 24 hours, and the cytotoxicity was determined using the CCK-8 assay.
RESULTS: RU.521 inhibited cell growth (CC50=38.4 μM). [1] |
| In vivo | METHODS: To study the effect of RU.521 on sepsis, mice were intraperitoneally injected with RU.521 (5 mg/kg) (injected with LPS) in a single dose.
RESULTS: RU.521 enhanced cardiac function, reduced cardiac inflammation, oxidative stress and apoptosis, and alleviated the symptoms of sepsis in mice. [2] |
| Storage | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | 5% DMSO+40% PEG300+5% Tween 80+50% Saline : 2 mg/mL (4.82 mM)
DMSO : 126.3 mg/mL (304.17 mM), Sonication is recommended.
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| Keywords | signaling pathway | RU-320521 | RU.521 | RU 320521 | oxidative stress | Inhibitor | inhibit | inflammatory | dsDNA/cGAS | Cyclic GMP-AMP Synthase | cGAS |
| Inhibitors Related | Norharmane | 2',3'-cGAMP sodium | Cyclophosphamide hydrate | Quinacrine dihydrochloride | Elinafide | L82 | Clofazimine | Methoxsalen | NSC16168 | Cyclophosphamide | Crystal Violet | Deoxyribonucleic acid |
| Related Compound Libraries | DNA Damage & Repair Compound Library | Bioactive Compound Library | Multi-Target Compound Library | Inhibitor Library | NO PAINS Compound Library | Anti-Aging Compound Library | Immunology/Inflammation Compound Library | Bioactive Compounds Library Max |
United States
