2',3'-cGAMP sodium salt
[CAS# 2734858-36-5]

Identification

• Classification: Biochemical >> Inhibitor >> Metabolism
• Name: 2',3'-cGAMP sodium salt
• Synonyms: Disodium 2-amino-9-[(1R,6R,8R,9R,10S,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-dihydroxy-3,12-dioxido-3,12-dioxo-2,4,7,11,13,16-hexaoxa-3?5,12?5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one
• Molecular Formula: C₂₀H₂₂N₁₀Na₂O₁₃P₂
• Molecular Weight: 718.37
• CAS Registry Number: 2734858-36-5
• SMILES: C1[C@@H]2[C@H]([C@H]([C@@H](O2)N3C=NC4=C3N=C(NC4=O)N)OP(=O)(OC[C@@H]5[C@H]([C@H]([C@@H](O5)N6C=NC7=C(N=CN=C76)N)O)OP(=O)(O1)[O-])[O-])O.[Na+].[Na+]

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319
• Safety Statements: P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Discovery and Applications

2',3'-cGAMP sodium salt is a chemically synthesized cyclic dinucleotide that acts as a potent endogenous ligand of the Stimulator of Interferon Genes (STING) pathway, a crucial component of the innate immune response. The molecule 2',3'-cyclic GMP-AMP (2',3'-cGAMP) is composed of guanosine monophosphate (GMP) and adenosine monophosphate (AMP) linked through both 2'-5' and 3'-5' phosphodiester bonds. The sodium salt form of 2',3'-cGAMP is typically used in biochemical and biomedical research to increase its solubility and stability in aqueous solutions for experimental applications.

The discovery of 2',3'-cGAMP as an immune signaling molecule originated from investigations into the mechanisms by which host cells detect the presence of cytosolic DNA, often associated with viral or bacterial infections. Upon sensing double-stranded DNA in the cytosol, cyclic GMP-AMP synthase (cGAS) is activated and catalyzes the synthesis of 2',3'-cGAMP from ATP and GTP. This cyclic dinucleotide subsequently binds to and activates the STING protein, which is located on the endoplasmic reticulum membrane. STING activation leads to a cascade of downstream signaling events, including phosphorylation of TBK1 and IRF3, resulting in the production of type I interferons and other pro-inflammatory cytokines.

The endogenous role of 2',3'-cGAMP in host defense has prompted its use as a research tool and as a potential therapeutic agent in immuno-oncology and infectious disease. Synthetic 2',3'-cGAMP sodium salt is commonly utilized in laboratory studies to mimic the natural activation of STING signaling and to explore the effects of innate immune stimulation. It has been used in various models to assess antiviral responses, tumor immunity, and the regulation of inflammatory processes.

In cancer immunotherapy, the administration of 2',3'-cGAMP sodium salt has been studied for its ability to convert immunologically “cold” tumors into “hot” tumors by enhancing local immune cell infiltration and promoting antigen presentation. When injected intratumorally in preclinical models, 2',3'-cGAMP sodium salt has been shown to trigger STING-mediated activation of dendritic cells and cytotoxic T lymphocytes, leading to reduced tumor growth and, in some cases, systemic anti-tumor immunity. These effects have made STING agonists attractive candidates for combination with immune checkpoint inhibitors and other forms of cancer immunotherapy.

In the context of infectious diseases, 2',3'-cGAMP sodium salt is being studied for its ability to boost host defense mechanisms. Experimental models have shown that it can enhance resistance to certain viral infections by promoting interferon responses and inflammatory signaling. The capacity of 2',3'-cGAMP to amplify innate immune responses is also being investigated for the development of vaccine adjuvants, particularly in formulations designed to improve T cell immunity.

In addition to therapeutic research, 2',3'-cGAMP sodium salt is a valuable tool in basic science to study the STING pathway and its regulation. It is often used in assays involving cell lines engineered to express STING or cGAS, and its effects are measured using techniques such as quantitative PCR, western blotting, and ELISA to monitor cytokine expression and signal transduction.

The chemical synthesis and formulation of 2',3'-cGAMP sodium salt have been optimized to ensure high purity and biological activity. Commercially available preparations are used in both in vitro and in vivo research. Although the compound itself is not yet approved as a therapeutic drug, it serves as the basis for the design of novel STING agonists that are being tested in clinical trials.

References

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