XL-3158

Description

XL-3158 is a selective and cross-species Cyclic GMP-AMP synthase cGAS inhibitor IC50: 11.1 ?M for human cGAS, 2.19 ?M for mouse cGAS . XL-3158 simultaneously occupy allosteric and orthosteric sites, stabilizing the activation loop in a closed, inactive conformation and thereby attenuating the cGAS-DNA interactions. XL-3158 inhibits cGAS by targeting phase separation. XL-3158 efficiently penetrates cells by inhibiting aggregate formation, effectively reducing the local concentration of cGAS within cells. XL-3158 has no obvious cytotoxicity within the effective concentration range and is suitable for subsequent cell function experiments. XL-3158 overcomes species selectivity barriers and serves as a drug candidate for cGAS-dependent inflammatory diseases.