News | TargetMol

2023/12/22

WIKIMOLE—2',3'-cGAMP

2',3'-cGAMP，T10065/T10065L, is an endogenous cGAMP molecule in mammalian cells. The cGAMP molecule belongs to the cyclic dinucleotide (CDNs) family and exists in three different forms: 3′3′-cGAMP, 2′3′-cGAMP, and 3′2′-cGAMP. Due to its low solubility in water (solubility < 1 mg/mL), it is often prepared in the form of its sodium salt (solubility in H2O: 45.0 mg/mL, DMSO: 0.9 mg/mL) for scientific research purposes.

Mechanism of Action

2',3'-cGAMP can bind to STING, activating a cascade of downstream signaling events. The cGAS-STING signaling pathway serves as an intracellular surveillance system. When DNA from viruses or cancer cells enters the cytoplasm, cGAS (cyclic GMP-AMP synthase) is activated and catalyzes the synthesis of 2',3'-cGAMP from ATP and GTP. 2',3'-cGAMP acts as a warning signal, activating the STING (Stimulator of Interferon Genes) pathway. This ultimately induces the production of type I interferon (IFN-β) and other cytokines, initiating the immune response.

Biological Applications

2',3'-cGAMP, as the second messenger in the cGAS-STING signaling pathway, plays a crucial role in various pathological and physiological processes, including anti-infection, anti-tumor responses, autoimmune diseases, and inflammatory conditions. Consequently, the STING signaling pathway is a promising target for drug development. Additionally, the natural synthesis yield of 2',3'-cGAMP is low, and the phosphodiester bonds in its structure are susceptible to enzymatic degradation. Therefore, structural modifications of 2',3'-cGAMP to enhance stability contribute significantly to its pharmaceutical value.