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| Product Name: | RU.521 | | Synonyms: | RU.521;RU521;RU-320521;RU320521;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;RU.521 RU320521;inflammatory,oxidative stress,RU 320521,cGAS,RU-320521,Inhibitor,inhibit,RU.521,Cyclic GMP-AMP Synthase,signaling pathway;RU320521 RU-320521;RU32052 | | CAS: | 2262452-06-0 | | MF: | C19H12Cl2N4O3 | | MW: | 415.23 | | EINECS: | | | Product Categories: | | | Mol File: | 2262452-06-0.mol |  |
| | RU.521 Chemical Properties |
| Boiling point | 658.2±65.0 °C(Predicted) | | density | 1.73±0.1 g/cm3(Predicted) | | storage temp. | Keep in dark place,Sealed in dry,Store in freezer, under -20°C | | solubility | Soluble in DMSO (>25 mg/ml) | | form | solid | | pka | 6.17±0.30(Predicted) | | color | Off-white to pale pink | | Stability: | Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months. | | InChI | InChI=1S/C19H12Cl2N4O3/c1-8-13(16-9-4-2-3-5-10(9)18(27)28-16)17(26)25(24-8)19-22-12-7-6-11(20)14(21)15(12)23-19/h2-7,16,26H,1H3,(H,22,23) | | InChIKey | VIQXILLOJLATEF-UHFFFAOYSA-N | | SMILES | C1(=O)C2=C(C=CC=C2)C(C2=C(O)N(C3NC4=C(Cl)C(Cl)=CC=C4N=3)N=C2C)O1 |
| | RU.521 Usage And Synthesis |
| Description | RU.521 (2262452-06-0) 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. | | 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]. | | storage | Store at -20°C | | References | 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
[1] Jessica Vincent. “Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice.” Nature Communications (2017): 750.
[2] Caroline Wiser. “Small molecule inhibition of human cGAS reduces total cGAMP output and cytokine expression in cells.” Scientific Reports (2020): 7604. |
| | RU.521 Preparation Products And Raw materials |
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