GSK8612 is an inhibitor of TANK-binding kinase 1 (TBK1; IC50 = 158 nM).1 It is selective for TBK1 over a panel of 285 kinases. GSK8612 inhibits IFN-α release in isolated human peripheral blood mononuclear cells (PBMCs) stimulated with polyinosinic-polycytidylic acid (poly(I:C); IC50 = 794 nM). It also inhibits IFN-β secretion in THP-1 cells stimulated with dsDNA-containing baculovirus or cGAMP (IC50s = 1,258 and 501 nM, respectively). GSK8612 (5 mg/kg) reduces tumor volume and increases the number of tumor-infiltrating CD8+ T cells in immunocompetent, but not immunodeficient, mice in a model of carbon tetrachloride-induced hepatocellular carcinoma (HCC).2
1.Thomson, D.W., Poeckel, D., Zinn, N., et al.Discovery of GSK8612, a highly selective and potent TBK1 inhibitorMed. Chem. Lett.10(5)780-785(2019) 2.Jiang, Y., Chen, S., Li, Q., et al.TANK-binding kinase 1 (TBK1) serves as a potential target for hepatocellular carcinoma by enhancing tumor immune infiltrationFront. Immunol.12612139(2021)