2262452-06-0

Usage

Uses

Used in Immune System Regulation:
3-[1-(6,7-dichloro-1H-benzimidazol-2-yl)-5-hydroxy-3-methyl-pyrazol-4-yl]-3H-isobenzofuran-1-one is used as an inhibitor for [cGAS] in the [innate immune system] to [regulate the immune response to foreign cytoplasmic double-stranded DNA].
Used in Sepsis Treatment:
In the medical industry, 3-[1-(6,7-dichloro-1H-benzimidazol-2-yl)-5-hydroxy-3-methyl-pyrazol-4-yl]-3H-isobenzofuran-1-one is used as a therapeutic agent for [sepsis treatment] due to its ability to [significantly increase cardiac output in a mouse model of sepsis].
Used in Cell Line Research:
3-[1-(6,7-dichloro-1H-benzimidazol-2-yl)-5-hydroxy-3-methyl-pyrazol-4-yl]-3H-isobenzofuran-1-one is utilized as a research tool in [cell line research], particularly in [mouse and human cell lines], for [studying the activity and selectivity of cGAS inhibitors].

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

Upstream product

• 731773-32-3 ethyl 3-oxo-2-<3-oxo-1,3-dihydroisobenzofuran-1-yl>butanoate 
• 17700-09-3 4-nitro-1,2,3-trichlorobenzene 
• 65078-77-5 2,3-dichloro-6-nitroaniline 
• 1668-01-5 3,4-dichloro-1,2-phenylenediamine 
• 273930-54-4 4,5-dichloro-1,3-dihydrobenzimidazol-2-one 

Relevant academic research and scientific papers

Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice

Cyclic GMP-AMP synthase is essential for innate immunity against infection and cellular damage, serving as a sensor of DNA from pathogens or mislocalized self-DNA. Upon binding double-stranded DNA, cyclic GMP-AMP synthase synthesizes a cyclic dinucleotide that initiates an inflammatory cellular response. Mouse studies that recapitulate causative mutations in the autoimmune disease Aicardi-Goutières syndrome demonstrate that ablating the cyclic GMP-AMP synthase gene abolishes the deleterious phenotype. Here, we report the discovery of a class of cyclic GMP-AMP synthase inhibitors identified by a high-throughput screen. These compounds possess defined structure-activity relationships and we present crystal structures of cyclic GMP-AMP synthase, double-stranded DNA, and inhibitors within the enzymatic active site. We find that a chemically improved member, RU.521, is active and selective in cellular assays of cyclic GMP-AMP synthase-mediated signaling and reduces constitutive expression of interferon in macrophages from a mouse model of Aicardi-Goutières syndrome. RU.521 will be useful toward understanding the biological roles of cyclic GMP-AMP synthase and can serve as a molecular scaffold for development of future autoimmune therapies.