NCI 126224

NCI 126224 is a toll-like receptor 4 (TLR4) antagonist.¹ NCI 126224 selectively inhibits nitric oxide (NO) production induced by the TLR4 agonist LPS (IC₅₀ = 0.31 µM) over the TLR7/8 agonist R-848 , TLR1/2 agonist Pam₃CSK₄ , and TLR3 agonist poly(I:C) in RAW 264.7 macrophages but also inhibits NO production induced by the TLR2/6 agonist FSL-1 in the same cells at 0.6 µM. NCI 126224 inhibits LPS-induced NF-κB activity in a reporter assay using BV-2 microglial cells and LPS-induced increases in IL-1β and TNF-α levels in RAW 264.7 macrophages (IC₅₀s = 5.92, 0.42, and 1.54 µM, respectively).