cyclic dinucleotide

SN-011 (GUN35901) is a STING inhibitor, which inhibited the activation of the STING signal pathway and to prevent or treat a STING- mediated disease. It is a demethyl analogue of DUN99845.

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.

ADU-S100 (MIW815) is a cyclic dinucleotide (CDN) class STING agonist that significantly induces the production of IFN-β and pro-inflammatory cytokines TNF-α, IL-6, and MCP-1, induces TBK1 and IRF3 phosphorylation, and exhibits antitumour activity.

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

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).

3’,5’-DiOA-dC is a hydrophobic nucleotide lipid and acts as a ligand for the STING agonist c-di-GMP (CDG). It can assemble with CDG to form stable cyclic dinucleotide nanoparticles through molecular recognition-driven supramolecular forces. This interaction reduces tumor weight and volume while increasing the levels of CD8 T cells, neutrophils, and NK cells in the tumor microenvironment. Additionally, 3’,5’-DiOA-dC enhances TNF-α and IFN-γ levels in a mouse melanoma model.

CDN prodrug-1 (Compound 2) acts as a STING ligand. It is composed of a cyclic dinucleotide (CDN) linked by a diproline peptide. Once CDN prodrug-1 is internalized into lysosomes by cathepsins, it can be cleaved to release the parent CDN. Additionally, CDN prodrug-1 can be synthesized into nanoparticles for drug delivery research.

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, a selective and orally active non-nucleotide STING agonist with a dissociation constant (Kd) of 145 μM, demonstrates prolonged antitumor and immunogenic activity. It non-covalently binds to STING as a dimer, showing greater permeability compared to cyclic dinucleotide[1].

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. It can inhibit the activation of TMEM173 by the cyclic dinucleotide ligand cGAMP, suppress the activation of NF-κB, promote nucleosome remodeling, and lead to the degradation of the deacetylated (NuRD) complex proteins.

IACS-8803 Disodium, a potent cyclic dinucleotide STING agonist, exhibits strong systemic antitumor efficacy [1].

IACS-8803 diammonium, a potent cyclic dinucleotide STING agonist, demonstrates robust systemic antitumor efficacy [1].

CL845-PAB-Ala-Val-C5-MC, a conjugatable STING ligand, derives from the proprietary cyclic dinucleotide CL845 and is designed for bioconjugation.

CL845-PAB-Ala-Val-PEG4-Azide is a conjugatable STING ligand, synthesized from the proprietary cyclic dinucleotide [CL845]. It can be utilized for bioconjugation.

β-Nicotinamide adenine dinucleotide reduced dipotassium is an orally active, reduced coenzyme that functions as a donor of ADP-ribose units in ADP-ribosylation reactions and as a precursor of cyclic ADP-ribose. It also serves as a regenerative electron donor in essential cellular energy metabolism processes, including glycolysis, β-oxidation, and the tricarboxylic acid (TCA) cycle [1].

BI 7446 is a potent and selective cyclic dinucleotide (CDN)-based stimulator of interferon genes (STING) agonist capable of activating all five STING variants in cells, thus inducing tumor-specific immune-mediated tumor rejection. This compound is utilized in immuno-oncology research [1].

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) is a substrate of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), an enzyme abundantly found in the myelin. It is utilized in coupled enzyme assays for the quantification of CNP activity. At a concentration of 5 μM, 2',3'-cNADP disodium can enhance calcium release due to calcium overload and prevent calcium-induced swelling in rat brain mitochondria.