cGAS (cyclic GMP-AMP synthase)

Class

Small molecule cGAS inhibitor

Pathway

cGAS-STING type I interferon pathway

cGAS (cyclic GMP-AMP synthase) is an enzyme that functions as a sensor of DNA located outside the nucleus, in the cytoplasm of cells. Under normal circumstances, DNA should not be present in this compartment, so its detection there signals danger, such as viral infection or damage to the cell's own genetic material. When cGAS binds such DNA, it produces a small signaling molecule that activates a partner protein called STING, triggering production of type I interferons and other inflammatory mediators as part of the innate immune response. This pathway is essential for antiviral defense, but it can become chronically and inappropriately active when cells accumulate self-DNA in the cytoplasm, for example from genomic instability, mitochondrial stress, or leakage of nuclear material. Persistent activation of this pathway contributes to autoimmune and inflammatory conditions characterized by excessive interferon signaling, as well as to some age-related and neurodegenerative processes. A small molecule that inhibits cGAS is designed to dampen this DNA-sensing step directly at its source, reducing downstream interferon output in diseases driven by chronic innate immune activation, rather than addressing viral infection, where this pathway is protective.