CPD1578

CU-CPT-8m is a specific TLR8 antagonist, with an IC ₅₀ of 67±10 nM and negligible cytotoxicity. The K _d value of CU-CPT-8m is determined to be 220 nM. CU-CPT-8m only reduces the proinflammatory response in the TLR8-overexpressing cells strongly supports that CU-CPT-8m directly recognizes TLR8 in cells. It is particularly notable that TLR7 signaling is not affected at concentrations up to 75 μM. TLR7 and TLR8 are closely related and share many common ligands. Treatment of 1 μM CU-CPT-8m completely abolishes the elevation of TNF-α and IL-8 mRNA levels induced by R848. CU-CPT-8m inhibits R848-induced TNF-α production in the differentiated THP-1 monocytes cells in a dose-dependent manner with an IC ₅₀ of 90±10 nM, which is in good agreement with its IC ₅₀ value determined in HEK-Blue TLR8 cells.