cyclic dinucleotide

SN-011 (GUN35901) 是选择性 STING 抑制剂，可与环状二核苷酸 (CDN) 竞争 STING 二聚体的结合口袋，从而阻断 CDN 结合和 STING 激活。它用于 STING 驱动的自身免疫和炎症性疾病的研究，抑制 STING 信号传导的 IC50值为 76 nM。

2',3'-cGAMP是一种内源性环二核苷酸（CDN），是由cGAS(cGAMP synthase)响应细胞质中的双链DNA而产生。2',3'-cGAMP是一种STING激活剂和配体，进而通过TBK1/IRF3通路诱导IFNs，和通过NF-κB通路诱导促炎因子。

ADU-S100 (MIW815)是一种环二核苷酸(CDN)类的STING激动剂，可显著诱导IFN-β和促炎细胞因子TNF-α、IL-6、MCP-1的产生，诱导TBK1和IRF3磷酸化，具有抗肿瘤作用。

IACS-8803 is a potent cyclic dinucleotide STING agonist that exhibits strong systemic antitumor efficacy.

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。

3’,5’-DiOA-dC 是一种疏水性核苷酸脂质和 STING 激动剂 c-di-GMP（CDG）的配体。它可以与 CDG 结合，通过分子识别驱动的超分子力形成稳定的环状二核苷酸纳米颗粒。此复合物能减小肿瘤重量和体积，并增加肿瘤微环境中的 CD8 T 细胞、中性粒细胞和 NK 细胞数量。此外，3’,5’-DiOA-dC 还可以提升小鼠黑色素瘤模型中的 TNF-α 和 IFN-γ 水平。

CDN prodrug-1 (Compound 2) 是一种STING配体，由一个环状二核苷酸 (CDN) 和一个二丙氨酸肽连接体构成。该化合物在被组织蛋白酶内化到溶酶体后发生裂解，从而释放出母体 CDN。同时，CDN prodrug-1 可被合成为纳米颗粒，用于药物递送研究。

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).

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)

MSA-2 dimer is a selective, orally active non-nucleotide STING agonist (Kd=145 μM) with long-term antitumor and immunogenic activity. MSA-2 dimer is bound to STING as a non-covalent dimer exhibiting higher permeability than cyclic dinucleotide[1]. MSA-2 dimer (60 mg/kg; p.o.; 50 days) inhibits tumor growth and prolongs overall survival[1]. MSA-2 dimer (40 mg/kg; s.c.; 25 days) induces complete tumor regression[1].MSA-2 dimer (60 mg/kg; p.o.; 4 hours) increases proinflammatory cytokine (IFN-β) level in tumors[1].MSA-2 dimer (60 mg/kg; s.c.; 4 hours) concentrations is observed in tumors than in plasma or other nontumor tissues [1].MSA-2 dimer (THP-1 cells) induces phosphorylation of both TBK1 and IR. MSA-2 dimer (10 μM and 33 μM; macrophages) induces IFN-β[1].MSA-2 dimer also exhibits dose-dependent antitumor activity when administered by IT, SC, or PO routes[1]. [1]. Pan BS, et al. An orally available non-nucleotide STING agonist with antitumor activity. Science. 2020;369(6506):eaba6098.

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).

BPK-25 是一种活性丙烯酰胺，能够抑制环二核苷酸配体cGAMP对TMEM173的激活，抑制NF-κB的激活，促进核小体重塑，导致脱乙酰化 (NuRD) 复合物蛋白的降解。

IACS-8803 disodium 是一种高效环状二核苷酸的STING 激动剂，具有强大的全身抗肿瘤作用。

IACS-8803 diammonium 是一种高效环状二核苷酸的STING 激动剂，具有强大的全身抗肿瘤作用。

CL845-PAB-Ala-Val-C5-MC 是一种可结合的 STING 配体，由专有的环状二核苷酸 CL845 合成。CL845-PAB-Ala-Val-C5-MC 可用于生物偶联。

CL845-PAB-Ala-Val-PEG4-Azide 是一种可结合的 STING 配体，由专有的环状二核苷酸 CL845 合成。CL845-PAB-Ala-Val-PEG4-Azide 可用于生物偶联。

β-Nicotinamide adenine dinucleotide reduced dipotassium 作为一种口服有效的还原型辅酶，在ADP-核糖基转移酶反应中担任ADP-核糖单元的供体及环状ADP-核糖的前体。该化合物在细胞能量代谢，包含糖酵解、β-氧化及三羧酸(TCA)循环中，发挥重要的再生电子供体角色。

BI 7446 是一种基于环状二核苷酸 (CDN) 的高效、特异性STING (干扰素基因刺激蛋白) 激动剂。它能激活所有五种STING变体并在体外诱导肿瘤特异性的免疫介导反应，从而消除肿瘤。此化合物适用于免疫肿瘤学领域的研究。

C82 acts as an inhibitor of Mycobacterium tuberculosis (Mtb) cyclic dinucleotide phosphodiesterase (CdnP), with an IC50 value of 17.5 µM. This particular enzyme is responsible for breaking down cyclic di-AMP (c-di-AMP) into adenosine 5'-monophosphate (AMP). Notably, C82 demonstrates selectivity for Mtb CdnP over other bacterial cyclic dinucleotide phosphodiesterases (CDN PDEs) such as Yybt, RocR, and Group B Streptococcus (GBS) CdnP, as well as the mammalian CDN PDE ENPP1, and the viral CDN PDE poxin, showing effectiveness at a concentration of 200 µM.

2',3'-Cyclic NADP disodium (2',3'-cNADP+; β-Nicotinamide adenine dinucleotide-2',3'-cyclic phosphate) 是 2',3'-环状核苷酸 3'-磷酸二酯酶 (CNP) 的一种底物，CNP 在髓鞘中丰富存在。此化合物被用于偶联酶测定以量化 CNP 活性。使用 2',3'-Cyclic NADP disodium (5 μM) 可以增加钙超载引发的钙释放并防止大鼠脑线粒体发生钙诱导的肿胀。