STING agonist 22 is a novel, non-nucleotide specific small-molecule STING agonist with IC50 of 28, 11 uM for human STING isoforms WT and HAQ, respectively.STING agonist 22 did not show any cytotoxicity in an immune cell proliferation panel across a variety of immune cell types and also did not show any activity in a kinome panel.STING agonist 22 introduced higher levels of iFIT3 and MX1 mRNA across three different donors possessing different STING genotypes: WT/WT, WT/HAQ, and WT/R232H in human PBMCs (IC50=5-35 uM).STING agonist 22 demonstrated in vivo antitumor effect in an MC38 mice model, with STING pathway activation and production of type I IFNs and proinflammatory cytokines, serum levels of IL-6, G-SCF, and MIP-1β.
