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CAS No.: 1337532-29-2

GSK2656157 Catalog No. CSN15812

Synonyms: GSK2656157

GSK2656157 is an ATP-competitive inhibitor of PERK enzyme activity with an IC(50) of 0.9 nM and is highly selective for PERK with IC50 values > 100 nM against a panel of 300 kinases.

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400-920-2911

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tech@csnpharm.cn

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纯度 & 质量文件批次:

靶点选择性

生物活性

实验方案

技术信息

生物活性

靶点 PERK

IC50:0.9nM
描述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. GSK2656157 is a potent and selective PERK inhibitor with IC50 value of 0.9nM on PERK enzyme activity, highly selective for PERK with IC50 values >100nM against a panel of 300 kinases. Pretreatment with GSK2656157 at concentration ranging in 10-30nM resulted in block of UPR activated by thapsigargin or tunicamycin, including autophosphorylation of PERK and its downstream substrates as p-eIF2α, ATF4 and CHOP in BxPC3 cells. The transcription of a series of tunicamycin-induced UPR gene was attenuated by 1μM GSK2656157 in the same cell line, including CHOP, HERP, ERO1LB, DNAJB9, SEL1L, etc.. Complete inhibition of pPERK-Thr980 can be observed through 8h after a single oral dose of 50mg/kg GSK2656157 In vivo, which showed the pharmacokinetic properties of this compound, without effect on p-eIF2α-S51 level. Oral dose of 50mg/kg or 150mg/kg GSK2656157 twice daily resulted in varying degrees of tumor growth inhibition in mice bearing various human tumor xenografts, including by 61% tumor growth inhibition in BxPC3 pancreas xenografts, by 47% and 65% in NCI-H929 multiple myeloma xenografts, by 31% and 54% in HPAC pancreas xenografts and by 107% and 114% in Capan2 pancreas xenografts. After treatment with 50mg/kg or 150mg/kg GSK2656157 for 3 weeks, a decrease in blood vessel density in tumors can be observed in BxPC3 tumor-bearing mice^[1].
作用机制GSK2656157 is an ATP-competitive PERK inhibitor.^[1]
细胞研究

Cell Data

Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
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, IC50=0.03 μM	24900593

动物研究

剂量

Mice^[1] (p.o.): 1.5 mg/kg - 150 mg/kg

给药途径

p.o.

动物药代数据

Animal	Mice^[2]	Rats^[2]	Dogs^[2]
Dose	2 mg/kg	2.2 mg/kg	2.9 mg/kg
Administration	i.v.	i.v.	i.v.
AUC_0→inf	3270 ng·h/ml		3128.5 ng·h/ml
CL_b	10.5 ml/min/kg	9.5 ml/min/kg	15.5 ml/min/kg
AUC_0-inf		3921 ng·h/ml
Vd_ss	0.72 L/kg	0.6 L/kg	2.8 L/kg

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.4012 mL
- 12.0062 mL
- 24.0124 mL
- 5 mM
- 0.4802 mL
- 2.4012 mL
- 4.8025 mL
- 10 mM
- 0.2401 mL
- 1.2006 mL
- 2.4012 mL

技术信息

CAS号

1337532-29-2

储存条件

粉末: Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C23H21FN6O

运输

蓝冰

分子量

416.45

别名

GSK2656157

溶解度

DMSO	32.0 mg/mL (76.8 mM)
Water	Insoluble
Ethanol	Insoluble

动物实验配方

1% CMC Na+water

30 mg/mL

suspension

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