TLR1 (compound 4a) is a low molecular weight, cell-penetrating Toll/IL-1 receptor/resistance (TIR) domain/BB-Loop mimic. TLR1 inhibits IL-1 receptor-mediated responses.In Vitro: TLR1 inhibits IL-1β-induced phosphorylation of the mitogen-activated protein kinase p38 in EL4 thymoma cells and in freshly isolated murine lymphocytes in a concentration-dependent manner.In Vivo: TLR1 interferes with the interactions between mouse MyD88 and IL-1RI at the TIR domains. TLR1 produces a significant attenuation of the IL-1β-induced fever response (200 mg/kg, i.p.).