Cyclic GMP-AMP

• CAS: 849214-04-6
• Catalog Number: ACM-ONT849214046
• Category: Cyclic Dinucleotides
• Molecular Weight: 674.41
• Molecular Formula: C20H24N10O13P2

Case Study

Cyclic GMP-AMP for the Preparation of a STING-Activating Nucleobase Liposomal Nanovaccine

Dong W, et al. Colloids and Surfaces B: Biointerfaces, 2026, 262, 115540.

Cyclic GMP-AMP (cGAMP) was employed as an immune adjuvant to construct a STING-activating nanovaccine through nucleobase-lipid liposome encapsulation. In the preparation process, 490 μg of nucleobase lipid DTL was dissolved in chloroform and subjected to rotary evaporation to form a thin lipid film, followed by overnight vacuum drying. An aqueous solution containing 85.03 μg cGAMP in PBS (pH 7.2) was then added to hydrate the lipid film at room temperature. The mixture underwent ultrasonic treatment at 50 °C for 30 min to facilitate liposome formation and encapsulation of cGAMP, producing the nanovaccine formulation 2'3'-cGAMP@DTL. Subsequently, dialysis with a 1000 Da molecular weight cut-off membrane for 12 h removed unencapsulated molecules. The final formulation exhibited a DTL:cGAMP mass ratio of 6:1, demonstrating an efficient strategy for constructing STING-activating lipid nanovaccines for tumor immunotherapy.

Cyclic GMP-AMP for Investigating Transport Mechanisms in Tumor-Associated Immunity

Thöne FMB, et al. Journal of Biological Chemistry, 2026, 302(2), 111060.

cGAMP was used as a functional probe to investigate the transport mechanisms of tumor-derived immunomodulatory signals within the tumor microenvironment. Syngeneic mouse tumor models were established using MC38 and B16-F10 cells, including genetically modified variants deficient in cGAMP production or in the volume-regulated anion channel (VRAC) component LRRC8A. Comparative tumor growth studies were conducted in mice with selective LRRC8 subunit disruptions. Serum cytokine levels were quantified to evaluate systemic immune activation associated with cGAMP signaling. These experiments allowed assessment of VRAC-mediated cGAMP efflux from tumor cells and uptake by host cells. The results indicated that although tumor-derived cGAMP strongly suppresses tumor growth, its extracellular transport in vivo is largely independent of VRAC channels, suggesting the presence of alternative cGAMP transport pathways in tumor immunity.

Cyclic GMP-AMP for Bacterial-Mediated Intratracheal Drug Delivery in Lung Tumor Immunotherapy

Li Z, et al. Journal of Controlled Release, 2026, 391, 114606.

cGAMP was utilized as a STING agonist payload in a bacterial carrier system designed for targeted lung tumor immunotherapy. An engineered Salmonella strain (VNPDCX) with flagella overexpression and inducible lysis capability was developed to deliver cGAMP directly to orthotopic lung tumors via intratracheal administration. To monitor biodistribution, bacteria expressing tdTomato were administered to C57BL/6 mice at 10⁷ CFU per animal, followed by fluorescence imaging (λex/λem = 535/600 nm) 24 h post-administration. For visualization of drug delivery, fluorescently labeled cGAMP (cGAMP-Fluo) was administered either as a free molecule or conjugated to the bacterial carrier (VNPDCX-PAMAM-cGAMP-Fluo). Fluorescence signals (λex/λem = 490/530 nm) were subsequently detected in lung tissues and orthotopic tumors, confirming efficient tumor-targeted delivery of cGAMP using motile bacterial vectors.

Cyclic GMP-AMP for Modulating Oxidative Stress Pathways in an Ischemic Stroke Model

Li X, et al. Biochemical Pharmacology, 2025, 242, 117334.

cGAMP was investigated for its neuroprotective role in ischemic stroke using a mouse model of transient focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO). Following ischemic injury induction, cGAMP treatment was administered to evaluate its effects on oxidative stress and ferroptosis pathways. Neurological function and brain lesion size were assessed to determine therapeutic outcomes. Molecular analyses revealed that cGAMP activated the Nrf2/HO-1/GPX4 signaling axis, which regulates antioxidant defense and lipid peroxidation. To confirm pathway specificity, pharmacological inhibitors ML-385 (Nrf2 inhibitor) and ML-210 (GPX4 inhibitor) were applied, which abolished the protective effects of cGAMP. These experimental results demonstrated that cGAMP mitigates mitochondrial oxidative stress and ferroptosis independently of canonical cGAS-STING signaling, highlighting its potential as a regulator of redox homeostasis in ischemic injury.