Cayman Chemical cGAS Inhibitor Screening Assay Kit

Cayman Chemical’s cGAS Inhibitor Screening Assay Kit provides a robust and easy-to-use platform for identifying novel inhibitors of human cyclic GMP-AMP (cGAMP) synthase (cGAS), a key enzyme in the innate immune response to pathogenic dsDNA.

cGAS is a cytosolic mammalian nucleotidyltransferase that acts as a dsDNA sensor. Upon binding to pathogenic dsDNA, cGAS produces the cyclic dinucleotide second messenger cGAMP, which activates stimulator of interferon genes (STING), leading to activation of the type I IFN pathway as part of the innate immune response. Activation of cGAS and production of 2′3′-cGAMP are important in host defence but may play a role in the development of autoimmune diseases, such as systemic lupus erythematosus. Additionally, cGAS is activated in response to cancer-associated mitochondrial DNA leakage. Inhibition of cGAS activity decreases type I IFN production in patient-derived samples and mouse models of autoimmune diseases, indicating therapeutic utility of cGAS inhibition.

The cGAS Inhibitor Screening Assay Kit allows users to screen for modulators of cGAS activity using a straightforward two-stage method. In the first stage, a 30 min cGAS reaction is conducted, wherein active cGAS enzyme produces 2′3′-cGAMP in the presence of DNA, ATP and GTP. The addition of an effective inhibitor will suppress this reaction. In the second stage, a 2′3′-cGAMP ELISA is used to quantify the cyclic dinucleotide product of the cGAS reaction. This ELISA is a competitive assay with a range of 4.57–10,000 pM, a midpoint of approximately 300 pM (50% B/B₀) and a sensitivity (80% B/B₀) of approximately 50 pM.