UPR (unfolded protein response), dysregulation of which has been implicated in many important pathologies, is an essential pathway to cope with ER stress. PERK is one of three primary effectors of the UPR. It can be activated by the released ER chaperones caused by increase of unfolded proteins in the ER and thus phosphorylates eIF2α. GSK2606414 is a potent and selective PERK inhibitor with IC50 value of 0.4nM (measured by cytoplasmic PERK domain phosphorylation of EIF2α). Treatment with GSK2606414 at concentration ranging in 0.03-0.3μM for 2h can significantly inhibit p-PERK induced by 1μM thapsigargin with IC50 value<0.03μM in A549 cells. Oral administration of GSK2606414 at dose of 50mg/kg and 150mg/kg, b.i.d., for 21 days showed antitumor activity in a human pancreatic tumor xenograft model[1].
作用机制
The trifluoromethyl meta-substituent of GSK2606414 can occupy the PERK kinase domain.[1]
GSK2606414 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
human A549 cells
Function assay
2 h
Inhibition of thapsigargin-induced autophosphorylation of PERK in human A549 cells after 2 hrs by Western blotting
22827572
human A549 cells
0.03 μM
Function assay
2 h
Inhibition of thapsigargin-induced autophosphorylation of PERK in human A549 cells at 0.03 uM after 2 hrs by Western blotting
22827572
human A549 cells
Function assay
1 h
Inhibition of thapsigargin-induced autophosphorylation of PERK in human A549 cells preincubated for 1 hr followed by thapsigargin-induction measured after 1 hr by Western blotting analysis
Inhibition of thapsigargin-induced autophosphorylation of PERK in human A549 cells after 2 hrs by Western blotting
22827572
human A549 cells
0.03 μM
Function assay
2 h
Inhibition of thapsigargin-induced autophosphorylation of PERK in human A549 cells at 0.03 uM after 2 hrs by Western blotting
22827572
human A549 cells
Function assay
1 h
Inhibition of thapsigargin-induced autophosphorylation of PERK in human A549 cells preincubated for 1 hr followed by thapsigargin-induction measured after 1 hr by Western blotting analysis
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