Resatorvid (TAK-242) is a selective inhibitor of Toll-like receptor 4 (TLR4). Resatorvid inhibits IL-6, TNF-R and NO production (IC50s: 1.3 nM, 1.9 nM, and 1.8 nM).
Resatorvid suppresses the production of NO, TNF-α, and IL-6 from LPS-stimulated human peripheral blood mononuclear cells (PBMCs, IC50s: 11-33 nM). Resatorvid (1-100 nM; 15 minutes; PBMCs cells) markedly inhibits the LPS-induced phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2), p38, and JNK/SAPK as well as degradation of IκBβ at a concentration of 100 nM. Resatorvid (1-100 nM; 4 hours) inhibits mRNA expression of IL-6 and TNF-α induced by LPS and IFN-γ in RAW264.7 cells .
In ApoE knockout and wild-type mice, Resatorvid (0.3?mg/kg; intraperitoneal injection; twice a week; for 4 weeks) treatment inhibits serum autoantibodies (ANA and anti-dsDNA), cytokines (IFN-γ, TNF-α, IL-1β), lung inflammation, and intima-media thickness in brachiocephalic artery .