Extracellular signal-regulated kinases (ERKs) are protein kinase intracellular signaling molecules that participate in Ras-Raf-MEK-ERK signal transduction cascade, which is related with the regulation of various processes including cell adhesion, cell cycle progression, cell migration, cell survival, differentiation, metabolism, proliferation, and transcription[3]. VX-11e is an ERK inhibitor with IC50 value of 17 nM and 15 nM on ERK1 and ERK2, respectively[4]. While VX-11e was tested for cytotoxic activity on A549 and DM122, they EC50 value is 770 nM and 370 nM after four days of incubation. The ERK1/2 phosphorylation level analyzed by western blot assay showed enhancement at both 0.5 μM and 2μM of vx-11e[4]. In human melanoma RPDX tumor expanded NSG mice, the vx-11e was given 50 mg/kg BID for 2 weeks. VX-11 could inhibit the tumor growth significantly compared to control, and the PI3K expression level measured by western blot assay was inhibited in the tumor tissue[5].
作用机制
The vx-11e can bind with the inactive, unphosphorylated and active, phosphorylated ERK2. The equilibrium between the T and R-state conformers formed by the inhibitor with the inactive and active enzyme is strongly shifts to favor the R form. Thus, the allosteric properties of ERK2 endow the active form of the kinase with a novel capability of being inhibited through mechanisms involving conformational selection[6].
VX-11e 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
HT-29 cells
Proliferation assay
Antiproliferative activity against human HT-29 cells, IC50=0.048 μM
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