UM-203 is a reversible covalent STING antagonist effective against both mouse and human STING. It is particularly potent in inhibiting the common human STINGR232 variant. UM-203 prevents STING oligomerization and decreases the phosphorylation of downstream TBK1 and IRF3, thereby blocking the signaling pathways mediated by IRF3 and NF-κB, and inhibiting the secretion of IFNβ and IL-6. UM-203 is useful for research in inflammation and immunology, such as systemic lupus erythematosus.