CU-CPT22 is a specific small-molecule inhibitor of the TLR1/TLR2 complex with IC50 of 0.58 uM (NO production in RAW 264.7 cells).
CU-CPT22 preferentially inhibits TLR2/1 signaling, without affecting a panel of homologous TLRs (TLR2/6, TLR3, TLR4, and TLR7).
CU-CPT22 competes with the synthetic triacylated lipoprotein (Pam3CSK4) binding to TLR1/2 with high inhibitory activity and specificity.
CU-CPT22 demonstrated minimal non-specific inhibition against a panel of 10 representative kinases (PDGFRB, MET, DDR2, SRC, MAPK1, PAK1, AKT1, PKC-γ, CAMK1, and PLK4).
CU-CPT22 also inhibits the downstream signaling transduction in cellular assays, inhibits TNF-α (60%) and IL-1β (95%) at 8 uM in the Pam3CSK4-activated RAW 264.7 cells.
CU-CPT22 reduced the nuclear translocation of NF-κB and secretion of TNF-α from cultured primary mouse microglia.
CU-CPT22 also inhibits the downstream signaling transduction in cellular assays, inhibits TNF-α (60%) and IL-1β (95%) at 8 uM in the Pam3CSK4-activated RAW 264.7 cells.