SB24011 (SB 24011) is a selective small molecule inhibitor of the STING-TRIM29 E3 ligase interaction with IC50 of 3.85 uM in luciferase complementation assays, enhances cGAMP-mediated STING immunity.
SB24011 (10 uM) increases the cellular STING levels in A431 cells, via blocking K48-linkage specific ubiquitination induced by TRIM29.
SB24011 binds to STING and induces thermal destabilization of the dimeric STING within the cellular context, Lys224 and Arg238 of STING are two key residues that participate in the direct binding with SB24011.
SB24011-induced STING upregulation augments STING downstream immune responses, co-treatment of SB24011 with cGAMP enhanced the phosphorylation of STING, TBK1, and IRF3 as compared with the cGAMP-only-treated Raw264.7 cells, time-and dose-dependently enhanced the mRNA expression of type 1 interferon molecules, including interferon (IFN)-β, and proinflammatory cytokines, including interleukin (IL)-6, IL-15, and IL-15Rα.
SB24011 (1-3 ug, intratumoral injection) potentiates STING agonist cGAMP (1 μg)-based cancer immunotherapy in in vivo syngeneic mouse model of CT26 tumor.
SB24011 dose-dependently increased PD-L1 expression in CT26 cancer cells, increased the population of PD-1+CD8+T cells as well as PD-L1 expression in the TME of CT26 syngeneic mice.
SB24011 can potentiate cancer immunotherapy with anti-PD-1 as well as STING agonists.