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Description

A cell-permeable, end protected L-valyl derivative modeled on the MyD88-binding sequence of the TIR (Toll/IL-1R/resistance) domain BB-loop of IL-1RI (type I IL-1 receptor). It specifically inhibits TIR domain-mediated MyD88/IL1-RI interaction without affecting TLR4/MyD88 interaction. It was used successfully to reduce IL-1beta-induced fever in mice in vivo and to attenuate IL-1beta-induced, but not LPS-induced, activation of MAP kinase signaling cascades in murine lymphocytes and EL4 thymoma cells in vitro., A cell-permeable, end protected L-valyl derivative of the MyD88-binding sequence of the TIR (Toll/IL-1R/resistance) domain BB-loop of IL-1RI (type I IL-1 receptor). It specifically inhibits TIR domain-mediated MyD88/IL1-RI interaction without affecting TLR4/MyD88 interaction. It was used successfully to reduce IL-1beta-induced fever in mice in vivo and to attenuate IL-1beta-induced, but not LPS-induced, activation of MAP kinase signaling cascades in murine lymphocytes and EL4 thymoma cells in vitro.