c-Jun N-terminal kinase (JNK) is a serine threonine protein kinase that belongs to the mitogen-activated protein kinase family. SP-600125 is an anthrapyrazolone inhibitor of JNK with IC50 values of 40, 40, and 90nM for JNK1, JNK2, and JNK3, respectively. SP-600125 also exhibits inhibitory activity against p56Lck, MMK3, MMK4, MMK6, MM7, PKB/AKT, and PKCα with IC50 values of 4.3, 1.5, 0.4, 1.0, 5.1, 1.0, and 1.5μM, respectively. SP-600125 inhibited JNK2 in an ATP-competitive manner with a Ki value of 0.19±0.06μM. It inhibited the phosphorylation of c-Jun in Jurkat T cells with an IC50 value of 5-10μM. In cells stimulated with PMA and phytohemagglutinin, SP-600125 inhibited both IL-2 and IFN-γ expression in a dose-dependent manner with IC50 values of 6 and 7μM, respectively. The incubation of Th1 cells with SP-600125 for 5 days potently inhibited the expression of IFN-γ, TNF-α, and IL-10 (IC50 = 7-12μM), but only weakly blocked the production of IL-1β and IL-6 (IC50 > 30μM). In primary human peripheral blood mononuclear cells stimulated with LPS (100 ng/ml) for 4 h, treatment with SP-600125 dose-dependently inhibited the mRNA expression of COX-2 and TNF-α with IC50 values of 5 and 10μM. In CD-1 mice induced with LPS, intravenous administration of SP-600125 significantly decreased the serum level of TNF-α at doses of 15 and 30mg/kg, while oral administration of 30mg/kg SP-600125 significantly inhibited TNF-α expression compared to the vehicle-treated group[2].
作用机制
SP-600125 is a small-molecule, ATP-competitive inhibitor of JNK[1].
SP600125 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
A549
20 μM
Growth Inhibition Assay
72 h
Rapid and potent inhibition of cell proliferation
23912840
A549
20 μM
Function Assay
1 h
Inhibition of TPA-induced MMP-2 and u-PA expression
20492175
B16-F10
Function Assay
1 h
Inhibition of TNF-alpha-induced c-JUN phosphorylation
21815634
BV-2
2 μM
Function Assay
1 h
Inhibits the increase of sBAFF release in Gmix-treated BV-2 cells
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