AG-490

别名: Tyrphostin B42, Zinc02557947

AG-490是一种EGFR抑制剂,在无细胞试验中IC50为0.1 μM,作用于EGFR比作用于ErbB2选择性高135倍,对JAK2也有抑制作用,对Lck,Lyn,Btk,Syk和Src没有抑制活性。

AG-490 Chemical Structure

AG-490 Chemical Structure

CAS: 133550-30-8

规格 价格 库存 购买数量
10mM (1mL in DMSO) 790 现货
10mg 647.01 现货
25mg 819.84 现货
50mg 1449.63 现货
100mg 2760.17 现货
300mg 5872.23 现货
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AG-490相关产品

相关信号通路图

细胞实验数据示例

细胞系 实验类型 给药浓度 孵育时间 活性描述 文献信息(PMID)
SUPT1  Apoptosis Assay 50 μM 24/48 h enhances TRAIL-induces cell apoptosis
Jurkat  Apoptosis Assay 50 μM 24/48 h enhances TRAIL-induces cell apoptosis
SUPT1  Growth Inhibition Assay 50 μM 24/48/72 h enhances TRAIL-induces cell growth inhibition
Jurkat  Growth Inhibition Assay 50 μM 24/48/72 h enhances TRAIL-induces cell growth inhibition
PA-1 Function Assay 10 uM 1 h inhibits LPA-induced ovarian cancer cell motility
OVCAR-3 Function Assay 10 uM 1 h inhibits LPA-induced ovarian cancer cell motility
PA-1 Function Assay 10 uM 1 h inhibits LPA-induced STAT3 phosphorylation
OVCAR-3 Function Assay 10 uM 1 h inhibits LPA-induced STAT3 phosphorylation
A549 Function Assay 15 μm 1 h inhibits the phosphorylation of STAT1 on tyrosine 701 was detected 15 min after SPE B treatment
BMMC Function Assay 0-10 μM 15 min inhibits LTC4 release in a dose-dependent fashion with near complete inhibition at concentrations ⩾10 μM
THP1 Function Assay 10 uM 30 min  inhibits STAT3 tyrosine phosphorylation by over 60%
SW1990 Invasion Assay 20 μM 24 h reduces invasion of SW1990 cells 
SW1990 Function Assay 20 μM 24 h decreases the intensity of p-Stat3 expression
SW1990 Function Assay 20 μM 24 h decreases the expression of MMP-2 and VEGF mRNAs
SW1990 Growth Inhibition Assay 20 μM 24/48/72 h inhibits cell growth time dependently
MZ-304 Function Assay 50/100 μM 48 h reduces transcription of MMP genes and reduces enzymatic activity of MMPs
MZ-256 Function Assay 50/100 μM 48 h reduces transcription of MMP genes and reduces enzymatic activity of MMPs
MZ-54 Function Assay 50/100 μM 48 h reduces transcription of MMP genes and reduces enzymatic activity of MMPs
MZ-18 Function Assay 50/100 μM 48 h reduces transcription of MMP genes and reduces enzymatic activity of MMPs
A-172 Function Assay 50/100 μM 48 h reduces transcription of MMP genes and reduces enzymatic activity of MMPs
MZ-304 Function Assay 100 μM 48 h inhibits invasion
MZ-256 Function Assay 100 μM 48 h inhibits invasion
MZ-54 Function Assay 100 μM 48 h inhibits invasion
MZ-18 Function Assay 100 μM 48 h inhibits invasion
A-172 Function Assay 100 μM 48 h inhibits invasion
MZ-304 Function Assay 50/100 μM 48 h inhibits migration
MZ-256 Function Assay 50/100 μM 48 h inhibits migration
MZ-54 Function Assay 50/100 μM 48 h inhibits migration
MZ-18 Function Assay 50/100 μM 48 h inhibits migration
A-172 Function Assay 50/100 μM 48 h inhibits migration
MZ-304 Growth Inhibition Assay 50/100 μM 48 h leads to a statistically significant reduction of cell proliferation over a time period of 48 h
MZ-256 Growth Inhibition Assay 50/100 μM 48 h leads to a statistically significant reduction of cell proliferation over a time period of 48 h
MZ-54 Growth Inhibition Assay 50/100 μM 48 h leads to a statistically significant reduction of cell proliferation over a time period of 48 h
MZ-18 Growth Inhibition Assay 50/100 μM 48 h leads to a statistically significant reduction of cell proliferation over a time period of 48 h
A-172 Growth Inhibition Assay 50/100 μM 48 h leads to a statistically significant reduction of cell proliferation over a time period of 48 h
MZ-304 Function Assay 50/100 μM 48 h reduces the levels of constitutively activated STAT3 in a time-dependent and dose-dependent fashion
MZ-256 Function Assay 50/100 μM 48 h reduces the levels of constitutively activated STAT3 in a time-dependent and dose-dependent fashion
MZ-54 Function Assay 50/100 μM 48 h reduces the levels of constitutively activated STAT3 in a time-dependent and dose-dependent fashion
MZ-18 Function Assay 50/100 μM 48 h reduces the levels of constitutively activated STAT3 in a time-dependent and dose-dependent fashion
A-172 Function Assay 50/100 μM 48 h reduces the levels of constitutively activated STAT3 in a time-dependent and dose-dependent fashion
HEL Growth Inhibition Assay 100 μM 0-5 d reduces growth of JAK2V617F-expressing HEL cells
HEL  Function Assay 100 μM 12-72 h inhibits the level of p-JAK2, JAK2
KF8 Function Assay 10 μM  1 h  inhibits IL-33-induced IκBα degradation and NF-κB activation
KF8 Function Assay 10 μM  1 h inhibits IL-33-induced NF-κB activation
Hep-2 Function Assay 50 μM 24/48/72 h downregulates the STAT3, p-STAT3 and survivin protein levels
Hep-2 Function Assay 50 μM 24/48/72 h inhibits G1 to S cell cycle transition and induces G1 cell cycle arrest
Hep-2 Apoptosis Assay 50 μM 24/48/72 h induces cell apoptosis time dependently
Hep-2 Growth Inhibition Assay 25-100 μM 24/48/72 h inhibits cell growth in both time and dose dependent manner
HSC-T6 Function Assay 10 μM 2 h  inhibits the expressions of pY-STAT1 and Bad induced by CDE
HSC-T6 Apoptosis Assay 10 μM 2 h  inhibits the apoptosis of HSC-T6 cells induced by CDE
ARPE-19 Function Assay 5 μM 30 min inhibits JAK2 phosphorilation
HT29 Function Assay 100 µM  24/48/72 h decreases the pSTAT3 levels in a time-dependent manner 
SW1116 Function Assay 100 µM  24/48/72 h decreases the pSTAT3 levels in a time-dependent manner 
HT29 Function Assay 100 µM  24/48/72 h decreases the expression of JAK2 and pJAK2 time-dependently
SW1116 Function Assay 100 µM  24/48/72 h decreases the expression of JAK2 and pJAK2 time-dependently
RPE  Function Assay 30 µM  3 h inhibits the induction of p-STAT3 expression
SW620  Function Assay 20 µM 1/6 h inhibits p-STAT3 activation
NRK-52E  Function Assay 5 μM 30 min attenuates Ang-(1–7)-inhibited TGF-β1 mRNA at 16 h 
BV-2  Function Assay 20 µM 16 h inhibits LPS-induced STAT1 phosphorylation with almost completely diminished iNOS expression
HUVECs Apoptosis Assay 20 µM 4 h significantly decreases the cell apoptotic index
HUVECs Cell Viability Assay 20 µM 4 h attenuates H2O2-induced cell shrinkage and improved the attachment rate of the cells
A549  Function Assay 10/20/40 μM 24 h suppresses the radiation-induced elevation of VEGF 
A549  Function Assay 20/40 μM 20 h 20 μM AG490 suppresses the radiation-induced invasion of A549 cells
RAW264.7 Function Assay 50 μM 24/48 h inhibits RANKL-induced NFATc1 expression and phosphorylation of Ser727STAT3
RAW264.7 Growth Inhibition Assay 0-50 μM  48 h causes an arrest of RAW264.7 cells at the G0/G1 phase of the cell cycle
RAW264.7 Growth Inhibition Assay 0-50 μM  48 h inhibits cell growth dose-dependently
RAW264.7  Function Assay 50 μM  24/48 h suppresses RANKL-induced osteoclastogenesis
HepG2  Function Assay 100 μM 12/24 h inhibits STAT3 tyrosine phosphorylation
7TD1-WD-90  Function Assay 50 μM 6 h significantly inhibits the phosphorylation of JAK2 and phosphorylation of STAT3
7TD1-WD-90 Apoptosis Assay 50 μM 48 h induces apoptosis
7TD1-DXM Apoptosis Assay 50 μM 48 h induces apoptosis
7TD1-WD-90 Growth Inhibition Assay 10 μM 72 h inhibits cell growth
7TD1-DXM Growth Inhibition Assay 10 μM 72 h inhibits cell growth
MC3T3-E1  Function Assay 50 μM 4 h inhibits HSE-induced BMP7 and GHR protein expression 
AGS  Function Assay 50 μM 24/48/72 h the cytoplasmic localization of pJAK2 (JAK2 phosphorylated at residues Tyr1007 and Tyr1008) decreased after AG490 treatment for 24 and 48 hr, but started to rebound at 72 hr
SGC7901 Function Assay 50 μM 24/48/72 h the cytoplasmic localization of pJAK2 (JAK2 phosphorylated at residues Tyr1007 and Tyr1008) decreased after AG490 treatment for 24 and 48 hr, but started to rebound at 72 hr
AGS  Function Assay 50 μM 24/48/72 h the levels of pJAK2 began to decline at 24 hr, and rebounded at 72 hr 
SGC7901 Function Assay 50 μM 24/48/72 h the levels of pJAK2 began to decline at 24 hr, and rebounded at 72 hr 
AGS  Cell Viability Assay 0-100 μM 24/48/72 h causes a significant reduction in cell viability dose-dependently but not time-dependently
SGC7901 Cell Viability Assay 0-100 μM 24/48/72 h causes a significant reduction in cell viability dose-dependently but not time-dependently
HepG2 Function Assay 50-500 μM 60 min inhibits the IL-6-induced phosphorylation of STAT1 (Tyr705) and STAT3 (Tyr705) in a dose-dependent manner
EJ Function Assay 50/80 μM 48 h downregulates c-Myc, cyclinD1, survivin and VEGF expressions
EJ Growth Inhibition Assay 50/80 μM 48 h causes S-phase arrest
EJ Growth Inhibition Assay 50/80 μM 24/48/72 h inhibits cell growth in both time and dose dependent manner
HSC  Function Assay 20 μM 1 h abrogates the differential effects of leptin or AGEs
NRK-52E Function Assay 1 µM 10 min blocks Ang II induced CD24 expression
NRK-52E Function Assay 1 µM 10 min blocks the stimulatory effect of Ang II on Pax-2 expression 
GL37  Cell Viability Assay 0-10 µM 48 h suppresses La expression
TRPM2/HEK  Function Assay 10 µM 40 min reduces TRPM2 activation even at high concentrations of H2O2
U937  Function Assay 0.1–25 µM 15 min reduces H2O2-induced Ca2+increase in a concentration-dependent manner, and the IC50 value was 0.4 µM
TRPM2/HEK  Function Assay 0.1–25 µM 15 min reduces H2O2-induced Ca2+increase in a concentration-dependent manner, and the IC50 value was 1.7 µM
B16-F0 Function Assay 50/100 µM 48 h reduces anoikis resistance
SK-MEL-2 Function Assay 50/100 µM 48 h reduces anoikis resistance
SK-MEL-5 Function Assay 50/100 µM 48 h reduces anoikis resistance
MeWo Function Assay 50/100 µM 48 h reduces anoikis resistance
SK-MEL-28 Function Assay 50/100 µM 48 h reduces anoikis resistance
BCBL1 Function Assay 100 µM 24 h induces a complete autophagic flux 
BC3 Function Assay 100 µM 24 h induces a complete autophagic flux 
BCBL1 Function Assay 100 µM 24 h mediates de-phosphorylation of STAT3 correlated with HSP70 and HSF2 reduction
BC3 Function Assay 100 µM 24 h mediates de-phosphorylation of STAT3 correlated with HSP70 and HSF1 reduction
BCBL1 Function Assay 100 µM 24 h mediates PEL cell apoptosis
BC3 Function Assay 100 µM 24 h mediates PEL cell apoptosis
点击查看更多细胞系数据

生物活性

产品描述 AG-490是一种EGFR抑制剂,在无细胞试验中IC50为0.1 μM,作用于EGFR比作用于ErbB2选择性高135倍,对JAK2也有抑制作用,对Lck,Lyn,Btk,Syk和Src没有抑制活性。
靶点
JAK2 (V617F) [8] EGFR [1]
(Cell-free assay)
0.1 μM
体外研究(In Vitro)
体外研究活性

AG-490抑制EGF依赖的HER 14细胞增殖,IC50为3.5 μM。[1] 与特异性作用于前B细胞急性白血病(ALL)细胞抑制组成型激活的JAK2 相一致,5 μM AG-490通过诱导程序性细胞死亡,几乎完全抑制所有ALL 细胞生长,而对正常造血功能不会造成有害影响。AG-490不会抑制Lck, Lyn, Btk, Syk, 和 Src激活。[2]AG-490 (60-100 μM) 抑制Stat3sm组成型激活,且抑制自发的或白细胞介素2诱导的蕈菌(MF)肿瘤细胞生长 ,IC50分别为75 μM和 20 μM。[3]通过抑制JAK3和 STAT5a/b.的活性,AG-490有效抑制IL-2调节的人 T 细胞生长, IC50 为 25 μM。[4] AG-490 作用于MOPC, MPC11, 和S194细胞 ,显著抑制Stat3 组成型激活,导致显著的细胞凋亡,这种作用存在剂量依赖性。[6] AG-490 (100 μM) 抑制Akt磷酸化, 抑制核因子-κB激活, 且激活GSK-3β,导致c-Myc降低。AG-490 (50 μM)可以诱导表达Bcr-Abl 突变型T315I 和E255K 的BaF3细胞凋亡。[7] 30 μM AG-490 不仅抑制Epo诱导的野生型JAK2磷酸化,也抑制 组成型的JAK2 V617F突变型磷酸化。AG-490作用于BaF3细胞,有效抑制JAK 2 V617F 突变诱导的细胞因子非依赖的细胞生长。[8]

激酶实验 体外激酶自磷酸化检测
AG-490溶于DMSO 10%-H2O-乙醇 45%。原油膜提取物 (0.125 μg/mL)与EGF (20 nM) 在50 mM HEPES buffer, pH 7.6, 和125 mM NaCl中在 4oC下预温育15分钟。在V形 96孔板上进行 EGFR 或 ErbB2激酶自磷酸化活性检测,在4oC 进行30分钟。在含反应混合物(12 μL, 50mM, HEPES, pH 7.4,125 mM NaCl, 12 mM M8Ac2, 2 mM MnCl2, 1 mM NaVO3, 1 μM ATP, 及1 μCi[γ-32P]ATP,) 及浓度不断增高的AG-490 (4 μL)的每孔中加入膜抽提物(8 μL)。加入热样本缓冲液终止反应,样本在6% SDS-聚丙烯酰胺凝胶电泳微小胶体上跑胶,然后烘干凝胶,在线性处理时间进行自显影。扫描受体带,然后通过Ez-Fit 程序分析结果。 为了分析 JAK2, JAK2的自磷酸化,使用从G2期细胞得到的裂解物抗JAK2抗体,进行免疫沉淀,与浓度不断增高的AG-490(0-50 μM)预处理16小时。免疫复合物与抗磷酸抗体进行免疫印迹。通过测量JAK2自磷酸化而测定对体外激酶活性的抑制情况。
细胞实验 细胞系 Pre-B ALL
浓度 溶于DMSO, 终浓度为~ 50 μM
孵育时间 16小时
方法

使用不同浓度AG-490 处理细胞16小时。为了测定细胞增殖,加入[3H]胸甘(1 μCi) 培养,6小时或更长时间以后终止培养。收集细胞,样本在液体闪烁计数器上计数。

体内研究(In Vivo)
体内研究活性

AG-490处理,大幅降低 CD45+和HLA-DR+ 细胞数,作用于骨髓时,这两种细胞数分别从48% 和46%降低到不可检测水平,作用于未处理小鼠脾脏时,这两种细胞数分别从 38%和 22% 降低到不可检测水平。[2] 在体内,AG-490 处理,引起小鼠骨髓瘤细胞凋亡,但是不抑制IL-12诱导的巨噬细胞活化和IFN-γ产量。[6]与在体外抑制 JAK2 V617F 突变活性一致,AG-490每天按0.5 mg处理裸鼠 10天,高效抑制JAK2 V617F突变诱导的肿瘤形成和肿瘤细胞入侵。[8]

动物实验 Animal Models 静脉注射ALL 细胞的SCID小鼠
Dosages 每天0.85 mg + 0.5 mg
Administration 持续输液泵输液加之以每天腹腔注射
  • https://pubmed.ncbi.nlm.nih.gov/1676428/
  • https://pubmed.ncbi.nlm.nih.gov/8628398/
  • https://pubmed.ncbi.nlm.nih.gov/9192639/
  • https://pubmed.ncbi.nlm.nih.gov/10380915/
  • https://pubmed.ncbi.nlm.nih.gov/11264165/
  • https://pubmed.ncbi.nlm.nih.gov/12481410/
  • https://pubmed.ncbi.nlm.nih.gov/16818614/
  • https://pubmed.ncbi.nlm.nih.gov/19327411/

化学信息&溶解度

分子量 294.30 分子式

C17H14N2O3

CAS号 133550-30-8 SDF Download AG-490 SDF
Smiles C1=CC=C(C=C1)CNC(=O)C(=CC2=CC(=C(C=C2)O)O)C#N
储存条件(自收到货起)

体外溶解度
批次:

DMSO : 58 mg/mL ( (197.07 mM) ;DMSO吸湿会降低化合物溶解度,请使用新开封DMSO)

Ethanol : 9 mg/mL (30.58 mM)

Water : Insoluble

摩尔浓度计算器

体内溶解配方
批次:

现配现用,请按从左到右的顺序依次添加,澄清后再加入下一溶剂

动物体内配方计算器

实验计算

摩尔浓度计算器

质量 浓度 体积 分子量

动物体内配方计算器(澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)

mg/kg g μL

第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)

% DMSO % % Tween 80 % ddH2O
%DMSO %

计算结果:

工作液浓度: mg/ml;

DMSO母液配制方法: mg 药物溶于μL DMSO溶液(母液浓度mg/mL,:如该浓度超过该批次药物DMSO溶解度,请先联系Selleck);

体内配方配制方法:μL DMSO母液,加入μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入μL ddH2O,混匀澄清。

体内配方配制方法:μL DMSO母液,加入μL Corn oil,混匀澄清。

注意:1. 首先保证母液是澄清的;
2.一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。

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常见问题及建议解决方法

问题 1:
I would like to know whether AG490 (S1143) goes to CNS through BBB, or not?

回答:
AG-490 can go through the BBB. You can see this reference: http://bloodjournal.hematologylibrary.org/content/111/4/2062.full.html.

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