The extracellular signal-regulated kinase (ERK) pathway is a key signaling cascade involved in cell growth and proliferation. FR 180204 is a potent, selective ERK inhibitor that inhibits the kinase activity of ERK1 and ERK2 with IC50 values of 0.51 and 0.33 µM, respectively, and Ki values of 0.31 and 0.14 µM, respectively. FR 180204 also inhibits p38α with an IC50 value of 10 µM. FR180204 dose-dependently inhibited AP-1 transactivation in Mv1Lu cells with an IC50 of 3.1 µM[3]. Pretreatment of FR 180204 at 100 mg/kg (i.p., b.i.d.) significantly ameliorated the bodyweight loss and clinical arthritis in mice with collagen-induced arthritis (CIA). CIA mice treated with FR 180204 also showed a reduction (62%) in the plasma level of anti-type II collagen (CII) compared to the control group. In CII-immunized DBA/1 mice, FR 180204 (32 and 100mg/kg) decreased delayed-type hypersensitivity induced by CII-reactive T cells in a dose-dependent manner. It also inhibited in vitro CII-induced proliferation of lymph node cells prepared from CII-immunized mice[4].
作用机制
FR 180204 selectively inhibits ERK1/2 in an ATP-competitive manner. The novel hydrophobic interactions in FR180204/ERK complex attribute to the selectivity and potency of FR180204.
搜索
