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 是在细菌中发现的一种环二核苷酸 (CDN) ，可作为内源性第二信使，影响干扰素的产生以响应胞浆 DNA。cGAMP disodium 通过激活干扰素基因刺激因子 (STING)使 I 型干扰素和其他免疫介质的信号产生级联现象。cGAMP disodium 是一种有效的舌下免疫佐剂，能使免疫功能（血清抗 PA 中和和气道分泌物抗 PA SIgA 反应） 更好的发挥作用。

SR-717 是一种 cGAMP 的类似物，一种非核苷类 STING 激动剂，可以诱导 STING 形成“封闭”的激活构象。SR-717 具有抗肿瘤活性，可以促进免疫细胞的激活以及抗原的交叉提呈。

STING-IN-2 (C-170) 是一种 STING 共价抑制剂，可抑制小鼠 STING (mmSTING) 和人类 STING (hsSTING)，可用于自身炎症性疾病的研究。

2',3'-cGAMP sodium (2'-3'-cyclic GMP-AMP sodium) 是细胞天然免疫中第二信使，在 DNA 结合条件下由 cGAMP 合成酶 (cGAS) 催化形成。2',3'-cGAMP sodium 可与 STING 结合形成二聚体，诱导 IFN-β 及其他细胞因子的产生和表达。

2',3'-cGAMP (2'-3'-cyclic GMP-AMP) 是细胞天然免疫中第二信使，在DNA结合条件下由 cGAMP 合成酶 (cGAS) 催化形成。2',3'-cGAMP 可与 STING 结合形成二聚体，诱导干扰素-β（IFN-β）及其他细胞因子的产生和表达。

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 是一种内源性第二信使，通过触发干扰素的产生来响应胞浆 DNA。它通过激活干扰素基因刺激因子（STING），启动信号级联，进而导致I型干扰素及其他免疫介质的生成。

Mal-Val-Ala-PABA-cGAMP 是一款 ADC 连接剂，适用于与 STING 激动剂的结合。该化合物主要用于合成抗体-活性分子偶联物（ADCs）。

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).

cAIMP作为STING激动剂，在体外的哺乳动物细胞中，与标准的小鼠（DMXAA）和人类（2',3'-cGAMP）STING激动剂相比，cAIMP类似物能更强烈地激活STING依赖的IRF和NF-κB信号通路。在人类血液的离体实验中，它们能诱导I型干扰素（IFNs）和促炎细胞因子的产生。

cGAS-IN-4 (Compound 36) 是一种口服有效的环状 GMP-AMP 合酶 (cGAS) 抑制剂，对 h-cGAS 和 m-cGAS 的 IC50 分别为 32 nM 和 5.8 nM。在 THP-1 cell 细胞中，cGAS-IN-4 以 IC50 为 60 nM 抑制 cGAMP，从而提高细胞效能。在小鼠模型中，该化合物对 Concanavalin A 诱发的急性肝损伤展现抗炎作用。

Enpp-1-IN-25 (Compound 30) 是一种ENPP1抑制剂，IC50为8.05 nM，具有低口服生物利用度。通过抑制cGAMP的降解，Enpp-1-IN-25 能有效激活细胞内STING途径，并增强肿瘤微环境中免疫细胞的浸润和I型干扰素响应，从而提高抗PD-L1抗体的抗肿瘤效力。Enpp-1-IN-25 可用于癌症免疫疗法的研究。

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.1,2It has been used in the generation of lipid nanoparticles (LPNs). LPNs containing 93-O17O localize to the spleen after intravenous injection into mice.1LPNs containing 93-O17O have been used for the delivery of Cre recombinase and ribonucleoproteins for genome editing in mice and for the intratumoral delivery of cGAMP to enhance cross-presentation of tumor antigens.3,2 1.Zhao, X., Chen, J., Qiu, M., et al.Imidazole-based synthetic lipidoids for in vivo mrna delivery into primary T lymphocytesAngew Chem. Int. Ed. Engl.59(45)20083-20089(2020) 2.Chen, J., Qiu, M., Ye, Z., et al.In situ cancer vaccination using lipidoid nanoparticlesSci. Adv.7(19)eabf1244(2021) 3.Li, Y., Yang, T., Yu, Y., et al.Combinatorial library of chalcogen-containing lipidoids for intracellular delivery of genome-editing proteinsBiomaterials178652-662(2018)

93-O17S is a chalcogen-containing cationic lipidoid.1It 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 used 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.2 1.Li, Y., Yang, T., Yu, Y., et al.Combinatorial library of chalcogen-containing lipidoids for intracellular delivery of genome-editing proteinsBiomaterials178652-662(2018) 2.Chen, J., Qiu, M., Ye, Z., et al.In situ cancer vaccination using lipidoid nanoparticlesSci. Adv.7(19)eabf1244(2021)

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 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.

Enpp-1-IN-17 (example 274) 是一种ENPP1抑制剂，其对cGAMP水解的Ki值在100 nM-1 μM范围内，而对ATP水解的Ki值则大于1 μM。该化合物在抑制cGAMP水解方面相对于ATP水解的选择性比率超过6.4。