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Chemical Structure| 2262452-06-0 Chemical Structure| 2262452-06-0

Structure of RU.521
CAS No.: 2262452-06-0

Chemical Structure| 2262452-06-0

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RU.521 (RU320521) is a potent and selective inhibitor of cyclic GMP-AMP synthase (cGAS), inhibiting cGAS-mediated interferon upregulation with an IC50 of 0.7 μM. It also reduces interferon expression in macrophages from a mouse model of Aicardi-Goutières syndrome (AGS).

Synonyms: RU320521; RU-521

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Product Details of RU.521

CAS No. :2262452-06-0
Formula : C19H12Cl2N4O3
M.W : 415.23
SMILES Code : ClC1=C2C(N=C(N3C(O)=C(C4OC(C5=C4C=CC=C5)=O)C(C)=N3)N2)=CC=C1Cl
Synonyms :
RU320521; RU-521
MDL No. :MFCD32173679
InChI Key :IAWZUQAOMURCLV-UHFFFAOYSA-N
Pubchem ID :135397653

Safety of RU.521

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
RAW macrophage cells 700 nM 24 hours To evaluate the efficacy of RU.521 in suppressing cGAS-mediated interferon upregulation, results showed that RU.521 effectively inhibited dsDNA-activated cGAS activity. PMC5622107
RAW264.7 cells 5μM 24 hours RU.521 completely neutralized ALDH2-deficiency-induced macrophage polarization. PMC11388276
BV2 microglia 1 µM 30 minutes RU.521 pre-treatment robustly inhibited sevoflurane-induced NLRP3 inflaμMasome activation. PMC10929193
MLE12 cells 500 ng/mL 12 hours To evaluate NETs-induced necroptosis in MLE12 cells, results showed that NETs induced necroptosis in MLE12 cells by activating the cGAS-STING pathway PMC11414388
Human aortic endothelial cells (HAECs) 3μM 48 hours To investigate the effect of RU.521 on D-GAL-induced senescence in HAECs, results showed that RU.521 partially reversed the D-GAL-induced decrease in eNOS expression and increase in senescence markers PMC9662267
Raw-Lucia ISG cells 10 μM 2 hours To evaluate the inhibitory effect of RU.521 on cGAS-mediated signaling, the results showed that RU.521 could inhibit ISD-stimulated cGAS activation with an IC50 of 2.41 ± 0.87 μM. PMC10043009
MLE12 cells 10 µM 30 minutes To evaluate the role of RU.521 in CdCl2-induced pyroptosis of MLE12 cells, results showed that RU.521 significantly down-regulated STING protein expression, phosphorylation levels of TBK1 and NF-κB p65, and reduced the expression of pyroptosis-related proteins. PMC11414388

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
C57BL/6J mice Cerebral venous sinus thrombosis (CVST) model Intranasal administration 5 mg/kg every 2 days for 4 times RU.521 decreased the levels of 2′3′-cGAMP, STING, and downstream inflammatory cytokines, and suppressed the expressions of NLRP3 inflammasome and pyroptosis-related components. Additionally, RU.521 treatment reduced oxidative stress, lessened the numbers of microglia and neutrophils, and ameliorated neuronal apoptosis, degeneration, and neurological deficits post-CVST. PMC9188164
Mice Postoperative cognitive dysfunction (POCD) model Intraperitoneal injection 450 µg/kg Once daily for 7 days RU.521 attenuated cognitive dysfunction and NLRP3 inflammasome activation in mice by inhibiting the cGAS-STING pathway. PMC10929193
C57BL/6N mice APAP-induced liver injury model Intraperitoneal injection 30, 60, 90 mg/kg Once daily for 14 or 28 days To evaluate the therapeutic effect of RU.521 in APAP-induced liver injury, the results showed that the combination of RU.521 and recombinant IL-33 significantly improved liver injury, reduced serum ALT/AST levels, and improved survival rate. PMC10116723
C57BL/6J mice Acute lung injury model Intraperitoneal injection 200 μg/kg Single injection, lasting 36 hours To evaluate the protective effect of RU.521 on NETs-induced acute lung injury, results showed that RU.521 alleviated NETs-induced necroptosis of alveolar epithelial cells and lung injury by inhibiting the cGAS-STING pathway PMC11414388
C57BL/6 mice Aging mouse model Intraperitoneal injection 10 mg/kg PR-619, 5 mg/kg cisplatin Daily PR-619, twice weekly cisplatin, for 36 days To investigate the effect of RU.521 on endothelial function in aging mice, results showed that RU.521 significantly improved endothelium-dependent vasodilation and reversed the increased expression of aging markers PMC9662267
Mice DSS-induced colitis model Intraperitoneal injection 100 mg/kg Daily administration To evaluate the therapeutic effect of RU.521 on DSS-induced colitis, the results showed that RU.521 could alleviate intestinal inflammation. PMC10043009
C57BL/6J mice Cadmium poisoning model Intraperitoneal injection 5 mg/kg/day Once daily for 6 months To evaluate the effect of RU.521 on cadmium exposure-induced lung injury and alveolar epithelial cell pyroptosis, results showed that RU.521 significantly alleviated lung injury and the expression of pyroptosis-related proteins. PMC11590492

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.41mL

0.48mL

0.24mL

12.04mL

2.41mL

1.20mL

24.08mL

4.82mL

2.41mL

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