Sanofi-14h is a selective inhibitor of the AGC family kinase SGK3, blocks DMXAA-stimulated IRF3-promoter activity with IC50 of 1.73 uM, inhibits IFNβ production under STING stimulation.
Sanofi-14h not only shows higher activity toward SGK3 as compared with SGK1 but also has significant activity against kinases such as S6K1 (P70S6K1) and MLK3.
Sanofi-14h blocks IFNβ mRNA induction in a dose-dependent manner with EC50 of 0.5-1 uM in RAW264.7 cells.
Sanofi-14h blocks the phosphorylation of TBK1 and IRF3, along with the dimerization and nuclear translocation of IRF3 following treatment with a STING agonist, thus blocking IFNβ gene induction.
Sanofi-14h blocks the recruitment of TBK1 and IRF3 into the STING complex. Sanofi-14h blocks IFNβ gene induction induced by STING ligands and HSV-1. Sanofi-14h blocks the STING-induced TBK1-IRF3 signaling cascade.
Sanofi-14h blocks DMXAA-stimulated interferon and ISG gene expression in macrophages.
Sanofi-14h disrupts inducible TBK1-STING interaction.
Sanofi-14h inhibits phosphorylation of TBK1 through an unknown mechanism preventing STING and IRF3 phosphorylation, dimerization, and nuclear translocation in the presence of 2′3′-cGAMP and DMXAA.