2',3'-cGAMP (Synonyms: 2'-3'-cyclic GMP-AMP)

2',3'-cGAMP is a specific agonist of the STING receptor, and its mechanism of action primarily involves activating the STING signaling pathway, promoting the production of interferons and inflammatory cytokines. 2',3'-cGAMP plays an important role in the innate immune pathway of mammals, responsible for the surveillance of cytoplasmic DNA. The K_d value of 2',3'-cGAMP binding to STING is 3.79 nM^[1]. 2',3'-cGAMP is commonly used in research on immune regulation, antiviral immunity, and cancer treatment.

In vitro, 2',3'-cGAMP (2.2, 4.4, 8.75, 17, 35 μM) treatment of PC 3 cells for 48 hours has an IC₅₀ value of 11.46 μM^[2]. Treating the PC 3 cell line with 2',3'-cGAMP (4 µg/ml) for 10 minutes activates STING^[3].

In vivo, 10 μg of 2',3'-cGAMP is as effective as 200 μg of PD-L1 antibody in combating melanoma in C57 BL/6 mice. Titration experiments show that 2',3'-cGAMP enhances the antitumor effect of the PD-L1 antibody in a dose-dependent manner^[4].

References:

[1] Zhang X, et al. Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Mol Cell. 2013 Jul 25;51(2):226-35. 

[2] Rezaei M .09-P53. Docetaxel Enhances the Expression of STING Protein in PC3 Prostate Cancer Cells, and cGAMP Attenuates This Effect[C]. Benchmarking an Artificial Intelligence Method for Fast Diagnosis of Rare Genetic Disease.2020.

[3] Hannes S , Karlowitz R , Wijk S J L V .The Smac mimetic BV6 cooperates with STING to induce necroptosis in apoptosis-resistant pancreatic carcinoma cells[J].Cell Death & Disease.2024.

[4] Wang, H. et al. cGAS is essential for the antitumor effect of immune checkpoint blockade. Proc. Natl Acad. Sci. USA 114, 1637–1642 (2017).