Biochem/physiol Actions

GSK8612 is a potent and highly selective tank-binding kinase-1 (TBK1) inhibitor (pIC₅₀ = 6.8; pK_d = 8.0 vs pK_a = 6.2/STK17B, 6.0/IKKε, 6.1/LRRK2, 6.0/FLT4, 5.8/ULK3, 5.7/BMP2K, 5.7/CSNK2A1, 5.6/CSNK2A2, 5.6/FLT4, 5.5/PIK3CD, ﹤5.5/more than 270 kinases). GSK8612 inhibits IFNβ secretion induced by dsDNA containing virus or STING ligand cGAMP (IC₅₀ = 1.25 & 0.5 µM, respectively; THP-1), as well as suppresses TLR3 ligand poly(I:C)-induced IRF3 Ser396 phosphorylation (IC₅₀ = 1 µM; Ramos) and IFNα release (IC₅₀ = 0.79 µM; human PBMCs), a IFN positive feedback response steming from IFNβ.