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。

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。

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 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.

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.