cyclic gmp-amp

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

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 (2'-3'-cyclic GMP-AMP) 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.

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

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)

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.

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

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].

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)

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.

Cyclic GMP is an endogenous second messenger that initiates interferon production in response to cytoplasmic DNA. It activates the stimulator of interferon genes (STING), triggering a signaling cascade that results in the production of type I interferons and other immune mediators. The conjugate of cyclic GMP and AMP, known as Cyclic-GMP-AMP, can induce the phosphorylation and nuclear translocation of IRF3, thereby enhancing antiviral immune responses. Additionally, Cyclic GMP may activate PDE to degrade cAMP, inhibit the myocardial calcium current ICa, and regulate cardiac contractility. The derivative 8-Br-cGMP exhibits antiplatelet activity, and Cyclic GMP is used in research related to antiviral immunity and cardiovascular diseases.

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.

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

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)

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].

8-CPT-Cyclic AMP (8-CPT-cAMP) sodium is a selective activator of cyclic AMP-dependent protein kinase (PKA) and a potent inhibitor of cyclic GMP-specific phosphodiesterase (PDE VA) with an inhibitory concentration (IC50) of 0.9 μM. It also inhibits PDE III and PDE IV while significantly activating Epac, demonstrating diverse pharmacological activities [1] [2].

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)

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).

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.