cGAS-IN-1 (compound C20), a flavonoid that acts as a Cyclic GMP-AMP Synthase (cGAS) inhibitor, demonstrates IC50 values of 2.28 μM for human cGAS and 1.44 μM for mouse cGAS. By inhibiting the abnormal activation of cGAS linked to numerous immune-mediated inflammatory diseases, cGAS-IN-1 possesses potential anti-inflammatory properties [1].

2',3'-cGAMP sodium (2'-3'-cyclic GMP-AMP sodium) is a second messenger in cellular innate immunity and is catalyzed by cGAMP synthase (cGAS) under DNA binding conditions. 2',3'-cGAMP sodium binds to STING to form a dimer, inducing the production and expression of interferon-β and other cytokines.

USP15-IN-1 is a potent USP15 inhibitor (IC50 is 3.76 μM). USP15-IN-1 showed high antiproliferative activity against non-small cell lung cancer and leukemia cells. USP15 is an interacting protein of cGAS, and USP15 can promote cGAS to recognize DNA and activate downstream signaling pathways.

2',3'-cGAMP (2'-3'-cyclic GMP-AMP) is a second messenger in cellular innate immunity and is catalyzed by cGAMP synthase (cGAS) under DNA binding conditions. 2',3'-cGAMP binds to STING to form a dimer, inducing the production and expression of interferon-β and other cytokines.

RU.521 (RU3205217) is a potent dsDNA inhibitor (IC50 : 700 nM), inhibition of the dsDNA pathway by RU.521 requires the presence of cGAS.

IRAK4-IN-4 (compound 15) inhibits cyclic GMP-AMP synthase (cGAS) with an IC50 of 2.1 nM.IRAK4-IN-4 is an interleukin-1 receptor–associated kinase 4 (IRAK4) inhibitor, has an IC50 of 2.8 nM.

XQ2B is a cGAS inhibitor that impedes protein-DNA interactions and phase separation. It suppresses antiviral immune responses induced by herpes simplex virus 1 (HSV-1) and augments HSV-1 infection in both in vitro and in vivo settings [1].

G108 is a Novel h-cGAS specific inhibitor for repression of dsDNA-triggered interferon expression (IC50 of 27.5 nM and 5150 nM for h-cGAS and m-cGAS, respectively).

Biotin-labeled ODN TTAGGG (sodium) is an inhibitory oligonucleotide (ODN) that functions as an antagonist to TLR9, AIM2, and cGAS. It serves as a tool for assessing cellular uptake and localization of CpG ODN using biotin detection systems and light microscopy.

FITC-labeled ODN TTAGGG (sodium) is an inhibitory oligonucleotide that functions as an antagonist of TLR9, AIM2, and cGAS. This compound facilitates the assessment of CpG ODN cellular uptake and localization via confocal laser-scanning microscopy (excitation at 495 nm, emission at 520 nm) or flow cytometry.

CU-32 is an inhibitor of cyclic GMP-AMP (cGAMP) synthase (cGAS; IC50= 0.45 μM).1It reduces DNA-, but not Sendai virus-, induced dimerization of IFN regulatory factor 3 in THP-1 cells, indicating selectivity for the cGAS DNA sensing pathway over the RIG-I-MAVS RNA sensing pathway. It is also selective for cGAS over toll-like receptors (TLRs) at 50 μM. CU-32 decreases IFN-stimulatory DNA-induced production of IFN-β in THP-1 cells when used at concentrations of 10, 30, and 100 μM. 1.Padilla-Salinas, R., Sun, L., Anderson, R., et al.Discovery of small-molecule cyclic GMP-AMP synthase inhibitorsJ. Org. Chem.85(3)1579-1600(2020)

SB02024 is a VPS34 inhibitor. SB02024 activates cGAS-STING signaling and sensitizes tumors to STING agonist. SB02024 blocked autophagy in vitro and reduced xenograft growth of two breast cancer cell lines, MDA-MB-231 and MCF-7, in vivo. Vps34 inhibitor significantly potentiated cytotoxicity of Sunitinib and Erlotinib in MCF-7 and MDA-MB-231 in vitro in monolayer cultures and when grown as multicellular spheroids. Our data suggests that inhibition of autophagy significantly improves sensitivity to Sunitinib and Erlotinib and that Vps34 is a promising therapeutic target for combination strategies in breast cancer.

SR-717 free acid is a stable cGAMP mimetic and a non-nucleotide STING agonist. It exhibits antitumor activity with EC50 values of 2.1 μM and 2.2 μM in ISG-THP1 (WT) and ISG-THP1 cGAS KO (cGAS KO) cell lines, respectively.

ODN TTAGGG (A151) is an inhibitory oligonucleotide (ODN), a TLR9, AIM2 and cGAS antagonist. oDN TTAGGG competitively inhibits AIM2 inflammasome activation by DNA and inhibits cGAS activation, exhibiting immunosuppressive activity. ODN TTAGGG can be used to study autoimmune diseases such as lupus erythematosus. oDN TTAGGG sequence: 5'-T-T-A-G-G-G-T-T-A-G-G-G-G-T-T-A-G-G-G-G-G-T-T-A-G-G-G-G-G-G-3'.

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)

PF-06928215 is an inhibitor of cGAS (cyclic GMP-AMP Synthase) (IC50 of 4.9 μΜ).

SU0268 is a potent and specific 8-Oxoguanine DNA glycosylase 1 (OGG1) inhibitor. SU0268 regulates inflammatory responses during Pseudomonas aeruginosa infection.

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).

G140 is a potent and selective inhibitor of cyclic GMP-AMP synthase (cGAS).

CU-76 is an inhibitor of cyclic GMP-AMP synthase (cGAS; IC50= 0.24 μM).1It reduces DNA-, but not Sendai virus-, induced dimerization of IFN regulatory factor 3 in THP-1 cells, indicating selectivity for the cGAS DNA sensing pathway over the RIG-I-MAVS RNA sensing pathway. CU-76 decreases IFN-stimulatory DNA-induced production of IFN-β in THP-1 cells when used at concentrations of 10, 30, and 100 μM. 1.Padilla-Salinas, R., Sun, L., Anderson, R., et al.Discovery of small-molecule cyclic GMP-AMP synthase inhibitorsJ. Org. Chem.85(3)1579-1600(2020)