TAK-242

TAK-242 is an antagonist of toll-like receptor 4 (TLR4) with an IC50 value of 0.68 µM in a secreted alkaline phosphatase (SEAP) assay.{60760} It selectively binds to TLR4 over TLR1-3 and TLR5-10 when used at a concentration of 100 nM.{28193} TAK-242 (1 µM) prevents the interaction of TLR4 with its adaptor proteins TIRAP or TRAM in HEK293 cells expressing the human receptors.{28193} It inhibits IFN-?- and LPS-induced production of nitric oxide (NO), TNF-?, IL-6, and IL-1? in isolated mouse peritoneal macrophages (IC50s = 5.7-11 nM), as well as inhibits LPS-induced NETosis in isolated human neutrophils when used at concentrations ranging from 5 to 20 µM.{28174,60761} TAK-242 (0.3, 1, and 3 mg/kg) improves survival in a mouse model of septic shock induced by LPS.{28192}