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GSK2606414

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纯度: 99.53%

货号 T2614Cas号 1337531-36-8

GSK2606414 是可渗透细胞且有口服活性的蛋白激酶 R 样内质网激酶抑制剂,IC50值为 0.4 nM。 GSK2606414抑制细胞中的 PERK 激活,并抑制小鼠人肿瘤异种移植物的生长。

GSK2606414
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GSK2606414

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Rating icon 很棒

纯度: 99.53%

货号 T2614Cas号 1337531-36-8

GSK2606414 是可渗透细胞且有口服活性的蛋白激酶 R 样内质网激酶抑制剂,IC50值为 0.4 nM。 GSK2606414抑制细胞中的 PERK 激活,并抑制小鼠人肿瘤异种移植物的生长。

规格价格库存数量
2 mg
¥ 592
现货
5 mg
¥ 921
现货
10 mg
¥ 1,255
现货
50 mg
¥ 3,525
现货
1 mL x 10 mM (in DMSO)
¥ 911
现货
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产品介绍


GSK2606414 AI Summary
GSK2606414 exhibits a broad spectrum of bioactivities, including potent inhibition of various kinases such as YES1, WNK2, AXL, TRKB, TRKA, and PERK with IC50 values ranging from 154.0 nM to 3195.0 nM. It shows antitumor activity in human BxPC3 cell xenografts in nude mice, with tumor growth inhibition percentages of 20.0% to 59.0% at different dosages, and demonstrates high oral bioavailability from 62.0% to 100.0% across different animal models. The compound's half-life ranges from 2.5 to 10.6 hours, and its volume of distribution at steady state varies from 3.8 to 8.2 L/kg. In addition to its kinase inhibition, GSK2606414 exhibits antiviral activity against SARS-CoV-2, reducing virus-induced cytotoxicity in Caco-2 cells by 85.4% at 10 µM and showing an IC50 value of 250.0 nM. It also inhibits SARS-CoV-2 3CL-Pro protease and displays selectivity with a selectivity index greater than 100.0, with low toxicity indicated by a CC50 value of 70350.0 nM. The compound effectively inhibits RIPK1 (IC50 of 18.0 nM) and demonstrates strong anti-necrotic activity in mouse L929 and MEF cells with IC50 values of 0.4 nM and 7.3 nM, respectively. It also exhibits anti-inflammatory effects in a mouse model of systemic inflammatory response syndrome (SIRS). Additional bioactivities include inhibition of cytochrome P450 enzymes, thapsigargin-induced autophosphorylation of PERK in human A549 cells (IC50 < 30 nM), and Toxoplasma gondii GST-tagged IF2Kalpha (IC50 of 0.4 nM). It also shows selective inhibition among NEK enzymes and modest inhibition of human HDAC6. Overall, GSK2606414 is a promising candidate with diverse pharmacological activities including kinase inhibition, antiviral, antitumor, anti-inflammatory, and antiparasitic effects..
Note: Summary generated by AI. Data source: ChEMBL
生物活性
产品描述
GSK2606414 is a cell-permeable and orally active protein kinase R-like endoplasmic reticulum kinase(PERK)inhibitor with IC50 of 0.4 nM. GSK2606414 inhibits PERK activation in cells and suppresses the growth of human tumor xenografts in mice.
靶点活性
EIF2AK3 (PERK):0.4 nM, N2A cells:5.3 μM, KIT (tyrosine kinase receptor):154 nM, EIF2AK1 (HRI):420 nM, ARPE-19 cells:1.7 µM, EIF2AK2 (PKR):696 nM
体外活性

方法:GSK2606414(0.1,1,3,10,30,100μM,72小时)处理S1-M1-80 载体和 S1-M1-80 sgABCG2 细胞,MTT法进行细胞毒性测定。
结果:GSK2606414 对两个细胞均显示出剂量依赖性细胞毒作用。[2]
方法:GSK2606414(0.5,1μM,24小时)和高葡萄糖 (30 mM) 处理 N2A 细胞,裂解细胞并进行免疫印迹分析。
结果:GSK2606414 处理的N2A 细胞降低了细胞中的 eIF2α 的磷酸化并以剂量依赖性方式显著降低 p-PERK 水平,GSK2606414 可以抑制 PERK/p-eIF2α/ATF4/CHOP 信号轴。[3]

体内活性

方法:GSK2606414(50,150mg/kg,口服,每天两次, 21 天)治疗携带皮下胰腺人类 BxPC3肿瘤的小鼠,观察对小鼠肿瘤生长的影响。
结果:GSK2606414 以剂量依赖性方式抑制肿瘤生长,两种剂量下,对小鼠肿瘤生长抑制率分别为 20% 和 59%。[1]

化学信息
分子量451.44
分子式C24H20F3N5O
CAS No.1337531-36-8
SmilesNC1=C2C(=CN(C)C2=NC=N1)C=3C=C4C(=CC3)N(C(CC5=CC(C(F)(F)F)=CC=C5)=O)CC4
密度1.43 g/cm3 (Predicted)
颜色White
物理性状Solid
储存&溶解度
存储Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
溶解度信息
DMSO: 130 mg/mL (287.97 mM), Sonication is recommended.
体内实验配方
10% DMSO+40% PEG300+5% Tween 80+45% Saline: 4 mg/mL (8.86 mM), Sonication is recommended.
请按顺序添加溶剂,在添加下一种溶剂之前,尽可能使溶液澄清。如有必要,可通过加热、超声、涡旋处理进行溶解。工作液建议现配现用。以上配方仅供参考,体内配方并不是绝对的,请根据不同情况进行调整。
溶液配制表
DMSO
1mg5mg10mg50mg
1 mM2.2151 mL11.0757 mL22.1513 mL110.7567 mL
5 mM0.4430 mL2.2151 mL4.4303 mL22.1513 mL
10 mM0.2215 mL1.1076 mL2.2151 mL11.0757 mL
20 mM0.1108 mL0.5538 mL1.1076 mL5.5378 mL
50 mM0.0443 mL0.2215 mL0.4430 mL2.2151 mL
100 mM0.0222 mL0.1108 mL0.2215 mL1.1076 mL

计算器

  • 摩尔浓度 计算器
  • 稀释 计算器
  • 配液 计算器
  • 分子量 计算器

体内实验配液计算器

请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法:
TargetMol | Animal experiments 比如您的给药剂量是10 mg/kg,每只动物体重20g,给药体积100 μLTargetMol | Animal experiments 一共给药动物10只,您使用的配方为5%TargetMol | reagent DMSO + 30%PEG300 + 5%Tween 80 + 60%Saline/PBS/ddH2O, 那么您的工作液浓度为2mg/mL
母液配置方法: 2 mg 药物溶于 50 μLDMSOTargetMol | reagent ( 母液浓度为 40 mg/mL ), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:50μLDMSOTargetMol | reagent 母液,添加 300 μLPEG300TargetMol | reagent 混匀澄清,再加 50μLTween80, 混匀澄清,再加 600μLSaline/PBS/ddH2OTargetMol | reagent 混匀澄清

以上为“体内实验配液计算器”的使用方法举例,并不是具体某个化合物的推荐配制方式,请根据您的实验动物和给药方式选择适当的溶解方案。

方案所需的各类助溶剂如: DMSOPEG300 / PEG400Tween 80SBE-β-CD玉米油 等, 均可在TargetMol网站点击购买。
1 请输入动物实验的基本信息
mg/kg
g
μL
2 请输入动物体内配方组成,不同的产品配方组成不同,如有配方需求,可先联系我们提供正确的体内配方。
% DMSO
%
% Tween 80
% Saline/PBS/ddH2O

剂量转换

对于不同动物的给药剂量换算,您也可以参考 更多

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