dsdna/cgas

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.

G150 inhibited interferon expression triggered by DSDNA with IC50 of 10.2 nM.G150 is an effective and highly selective inhibitor of human cyclic GMP-AMP synthase (H-CGAS).

PROTAC cGAS degrader-1 (Compound TH35) is a potent and selective cGAS PROTAC degrader, exhibiting DC50 values of 0.9 μM in THP-1 cells and 4.6 μM in RAW 264.7 cells. It effectively inhibits the activation of cGAS signaling induced by dsDNA. PROTAC cGAS degrader-1 also demonstrates anti-inflammatory properties, making it suitable for research into cGAS-related inflammatory diseases. (Pink: cGAS inhibitor; Black: Linker; Blue: E3 ligase ligand)

Cyclic di-UMP is a pyrimidine-containing cyclic dinucleotide (CDN).1It is produced by bacterial cGAS/DncV-like nucleotidyltransferases (CD-NTases), such as LpCdnE02 fromL. pneumophila, and binds to cGAS, in the apo or dsDNA-bound forms, with reduced affinity compared to 2'3'-cGAMP or 3'3'-cGAMP .1,2Cyclic di-UMP is intended for use as a negative control for cyclic di-GMP signaling. 1.Whiteley, A.T., Eaglesham, J.B., de Oliveira Mann, C.C., et al.Bacterial cGAS-like enzymes synthesize diverse nucleotide signalsNature564(7747)194-199(2019) 2.Hall, J., Ralph, E.C., Shanker, S., et al.The catalytic mechanism of cyclic GMP-AMP synthase (cGAS) and implications for innate immunity and inhibitionProtein Sci.26(12)2367-2380(2017)