gmp-amp

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

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

2',3'-cGAMP is an endogenous cyclic dinucleotide (CDN) produced by cGAS (cGAMP synthase) in response to double-stranded DNA in the cytoplasm. It acts as a STING activator and ligand, inducing interferons (IFNs) via the TBK1/IRF3 pathway and pro-inflammatory factors via the NF-κB pathway.

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).

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.

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

cGAMP is an endogenous second messenger in metazoans and triggers interferon production in response to cytosolic DNA. It also is a STING ligand.

Decoyinine (Decynylene), a selective inhibitor of GMP synthase, is a novel potential microbial insecticide, a secondary metabolite produced by Streptomyces hygroscopicus.Decoyinine induces resistance in rice to the small brown ladybug Laodelphax striatellus.

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.

cGAS-IN-4 (Compound 36) is an orally active inhibitor of cyclic GMP-AMP synthase (cGAS) with IC50 values of 32 nM for human cGAS (h-cGAS) and 5.8 nM for mouse cGAS (m-cGAS). In THP-1 cells, cGAS-IN-4 inhibits cGAMP with an IC50 of 60 nM, enhancing cellular potency. Additionally, cGAS-IN-4 exhibits anti-inflammatory effects in a mouse model of Concanavalin A-induced acute liver injury.

(R)-cGAS-IN-4 (Compound 77A*) is the R-enantiomer of cGAS-IN-4, which acts as an orally active inhibitor of cyclic GMP-AMP synthase-adenosine synthase (cGAS).

cGAS-IN-3 (compound 30d-S) is an orally active inhibitor of cyclic GMP-AMP synthase (cGAS) that exhibits excellent plasma exposure and low clearance rate. It demonstrates anti-inflammatory properties, significantly reducing pulmonary inflammation in rats.

cGAS-IN-7 is an inhibitor of the cyclic GMP-AMP synthase (cGAS) with an IC50 value of 0.66 μM for human cGAS. It moderately reduces cGAMP levels in THP1 cells and is applicable in Alzheimer's disease research.

cGAS-IN-8 is an indazole-based inhibitor of cyclic GMP-AMP synthase (cGAS), demonstrating an IC50 of 6 nM for human cGAS. It inhibits the production of cGAMP in THP-1 cells with an IC50 of 0.12 µM. Notably, cGAS-IN-8 does not inhibit hERG activity and is applicable in the study of autoimmune diseases.

8-CPT-Cyclic AMP sodium is an activator of cAMP-dependent PKA and cAMP receptor activator, and also an inhibitor of cAMP-specific phosphodiesterase (PDE VA) (IC50 = 0.9 μM). The IC50 values for PDE III and PDE IV are 24 and 25 μM, respectively.

5'-pApA is a linearized form of cyclic di-AMP, a bacterial second messenger that activates the host innate immune system through stimulator of interferon genes (STING).1,2,3,4It is a metabolite of cyclic di-AMP formedviahydrolysis by various phosphodiesterases (PDEs).55'-pApA is intended for use as a negative control for cyclic di-AMP signaling. 1.Burdette, D.L., Monroe, K.M., Sotelo-Troha, K., et al.STING is a direct innate immune sensor of cyclic-di-GMPNature478(7370)515-518(2011) 2.Parvatiyar, K., Zhang, Z., Teles, R.M., et al.DDX41 recognizes bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I interferon immune responseNat. Immunol.13(12)1155-1161(2012) 3.Woodward, J.J., Iavarone, A.T., and Portnoy, D.A.c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon responseScience328(5986)1703-1705(2010) 4.Witte, C.E., Whiteley, A.T., Burke, T.P., et al.Cyclic di-AMP is critical for Listeria monocytogenes growth, cell wall homeostasis, and establishment of infectionmBio4(3)e00282-00213(2013) 5.Fahmi, T., Port, G.C., and Cho, K.H.c-di-AMP: An essential molecule in the signaling pathways that regulate the viability and virulence of gram-positive bacteriaGenes (Basel)8(8)197(2017)

Cyclic di-IMP (sodium salt) (c-di-IMP) is a synthetic second messenger structurally related to the bacterial second messengers cyclic di-GMP and cyclic di-AMP . C-di-IMP has adjuvant properties when co-administered with antigens in vitro and by mucosal routes in vivo. C-di-IMP enriches the population of MHC class I and II, CD80, CD86, CD40, and CD54 positive dendritic cells derived from murine bone marrow. It also stimulates macrophages at 500 ng/ml. Mice immunized with β-galactosidase (β-gal) plus c-di-IMP through the intranasal route show a humoral immune response, evidenced by an increase in IgG titers up to 2-fold compared to mice immunized with β-gal alone. Mice immunized with β-gal plus c-di-IMP also exhibit a Th1/Th2 response, indicating that the adjuvant activity of c-di-IMP leads to a cellular immune response as well.

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)

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)

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)

Phosphoribosyl pyrophosphate pentasodium is the sodium salt form of PRPP. PRPP is a phosphoribosyl donor for AMP and GMP synthesis in reactions catalysed by adenine phosphoribosyltransferase and hypoxanthine/guanine phosphoribosyltransferase. PRPP is synthesized from ribose-5-phosphate and ATP by PRPP synthetase (EC 2.7.6.1).

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].

cGAS-IN-2 (compound 109) serves as a potent inhibitor of Cyclic GMP-AMP Synthase (cGAS), exhibiting an IC50 of 0.01512 μM against h-cGAS [1].

TDI-6570 is a cyclic GMP-AMP synthase (cGAS) inhibitor with an IC50 value of 0.138 μM.