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.

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.

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-SH is a ADC cytotoxin.

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.

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.

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

Enpp-1-IN-17 (example 274) is a potent inhibitor of ENPP1, with inhibition constants (Ki values) ranging from 100 nM to 1 μM for cGAMP hydrolysis and greater than 1 μM for ATP hydrolysis, demonstrating a selectivity ratio of over 6.4 favoring cGAMP hydrolysis inhibition [1].

Enpp-1-IN-19 (compound 29f) is an orally active inhibitor of ENPP1 that effectively blocks cGAMP hydrolysis with an IC50 of 68 nM. It not only enhances anti-PD-L1 responses and curtails tumor growth in CT26 syngeneic models but also boosts STING-mediated type I interferon responses. Additionally, Enpp-1-IN-19 fosters immune memory and aids in preventing tumor recurrence [1].