cgamp

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

cGAMP disodium is a cyclic dinucleotide (CDN) found in bacteria that acts as an endogenous second messenger affecting interferon production in response to cytoplasmic DNA. cGAMP disodium cascades signals from type I interferons and other immune mediators by activating interferon gene stimulator (STING). cGAMP disodium is a potent sublingual immune adjuvant that enables better immune function (serum anti-PA neutralization and airway secretions anti-PA SIgA response).

SR-717 is a cGAMP analog, a non-nucleoside STING agonist that induces a "closed" activation conformation of STING. SR-717 has antitumor activity and promotes activation of immune cells and cross-presentation of antigens.

STING-IN-2 (C-170) is a potent, covalent inhibitor of STING, effectively targeting both mouse (mmSTING) and human STING (hsSTING), and is applicable for autoinflammatory disease research.

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.

2'2'-cGAMP is a synthetic dinucleotide (CDN) that contains non-canonical 2'5'-phosphodiester bonds. It binds to the adapter protein stimulator of interferon genes , which is a component of the innate immune response that activates the type I interferon pathway when bound to cyclic dinucleotides. 2'2-cGAMP shows weaker binding to STING than 2'3'-cGAMP but binds more strongly than 3'3'-cGAMP , cyclic di-GMP , or 3'2'-cGAMP, which bind in the micromolar range (Kds = 1.04, 1.21, or 1.61 μM, respectively). Despite weaker binding, 2'2'-cGAMP induces IFN-β production in the same concentration range as 2'3'-cGAMP (EC50s = 15.8 and 19.4 nM, respectively, in L929 cells).

3'3'-cGAMP is a second messenger produced in bacteria by specific dinucleotide cyclases. It contains canonical 3'5'-phosphodiester bonds and regulates chemotaxis, colonization, and other cellular functions. 3'3'-cGAMP shows weaker binding to the adapter protein stimulator of interferon genes (STING; Kd = 1.04 μM) than 2'2'-cGAMP and 2'3'-cGAMP but has similar binding affinity to 3'2'-cGAMP (Kd = 1.61 μM) and cyclic di-GMP . 3'3'-cGAMP induces IFN-β mRNA expression in L929 cells (EC50 = 40.5 nM).

2',3'-cGAMP-C2-PPA (45) is a cyclic di-nucleotide that acts as a STING agonist (US20210015941A1). It is a drug-linker conjugate for antibody-drug conjugates (ADC) used in the targeted treatment of cancer.

3',3'-cGAMP sodium salt is a STING agonist. Reduces B cell proliferation and induces apoptosis of malignant B cellsin vitro. Suppresses 5TGM1 multiple myeloma xenograft growth in immunodeficient mice, and induces leukemic regression in Eμ-TCL1 mice.

cGAMP (Cyclic GMP-AMPP) diammonium serves as an intrinsic second messenger in metazoans, initiating the production of interferons upon cytosolic DNA detection. It activates the stimulator of interferon genes (STING), subsequently triggering a signaling cascade that culminates in the synthesis of type I interferons and various immune mediators [1] [2] [3] [4].

Mal-Val-Ala-PABA-cGAMP serves as an ADC linker for attachment to STING agonists and is utilized in the synthesis of antibody-drug conjugates (ADCs) [1].

cAIMP acts as a STING agonist and has been shown to more effectively activate STING-dependent IRF and NF-κB signaling pathways in mammalian cells in vitro when compared to standard murine (DMXAA) and human (2',3'-cGAMP) STING agonists. In ex vivo experiments with human blood, cAIMP analogs can induce the production of type I interferons (IFNs) and pro-inflammatory cytokines.

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.

Enpp-1-IN-25 (Compound 30) is an ENPP1 inhibitor with an IC50 of 8.05 nM and exhibits low oral bioavailability. By inhibiting cGAMP degradation, it effectively activates the intracellular STING pathway. Enpp-1-IN-25 can enhance immune cell infiltration and type I interferon response in the tumor microenvironment, thereby increasing the antitumor efficacy of anti-PD-L1 antibodies. It is applicable for research in cancer immunotherapy.

(S)-2-(1-Ethyl-3-methyl-1H-pyrazole-5-carboxamido)-1-(2-hydroxy-2-phenylethyl)-1H-benzo[d]imidazole-5-carboxamide (compound 4) is a STING agonist containing the crucial amide benzimidazole (ABZI) component. It consistently inhibits the binding of 3 H-cGAMP to STING, with an apparent inhibition constant (IC50) of 14 μM. This compound is applicable in tumor research.

STF-1084 is an inhibitor that cannot penetrate cells and targets ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (ENPP1) with an apparent Ki of 0.11 µM. It demonstrates selectivity for ENPP1 over ENPP2 and alkaline phosphatase (ALP) with apparent Kis of 5.5 and >100 µM, respectively, and does not affect a panel of 468 kinases at 1 µM. STF-1084 hinders the extracellular breakdown of cGAMP in ENPP1-overexpressing and cGAS-expressing 293T cells, with an IC50 of 0.340 µM, and enhances mRNA expression for the gene encoding IFN-β in CD14+ primary human peripheral blood mononuclear cells (PBMCs) when incubated with conditioned medium from ENPP1-overexpressing and cGAS-expressing 293T cells treated with STF-1084. In a live setting, STF-1084, when combined with ionizing radiation, elevates the proportion of tumor-associated CD11c+ cells among antigen-presenting cells (APCs) in a murine mammary cancer model (4T1).

STING-IN-8 (Compound 15b) is a potent inhibitor of the stimulator of interferon genes (STING), with an IC50 value of 0.121 μM in humans and 0.033 μM in mice. This compound effectively inhibits STING signaling induced by MSA-2 or 2',3'-cGAMP, as well as the levels of immune and inflammatory cytokines in human and mouse cells. STING-IN-8 shows significant potential for research in STING-related inflammatory and autoimmune diseases.

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)

STING18 is a competitive ligand of stimulator of interferon genes (STING; IC50 = 0.068 μM in a radioligand binding assay).1 It inhibits cGAMP-induced IFN-β production (IC50 = 11 μM) but does not stimulate IFN-β production (EC50 = >30 μM) in THP-1 cells. |1. Siu, T., Altman, M.D., Baltus, G.A., et al. Discovery of a novel cGAMP competitive ligand of the inactive form of STING. Med. Chem. Lett. 10(1), 92-97 (2019).

93-O17O is a chalcogen-containing cationic lipidoid used in the generation of lipid nanoparticles (LPNs). LPNs containing 93-O17O localize to the spleen after intravenous injection into mice and have been utilized for delivering Cre recombinase, ribonucleoproteins for genome editing, and intratumoral delivery of cGAMP to enhance cross-presentation of tumor antigens. [1,2,3]

93-O17S is a chalcogen-containing cationic lipidoid. It has been used in the synthesis of lipid nanoparticles (LPNs) for the delivery of Cre recombinase and ribonucleoproteins for genome editing in mice. LPNs containing 93-O17S have been utilized for the intratumoral delivery of cGAMP to enhance cross-presentation of tumor antigens and stimulation of interferon genes [STING] activation in a B16/F10 murine melanoma model.

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)

BPK-25 is an active acrylamide compound that enhances the degradation of proteins in the nucleosome remodeling and deacetylation (NuRD) complex through a post-translational mechanism involving covalent protein interaction. Additionally, BPK-25 acts as an inhibitor of TMEM173 activation by the cyclic dinucleotide ligand cGAMP.