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
CAS: 133550-30-8
产品质控
批次：
纯度：
99.99%
99.99
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 |
|---|---|---|---|---|---|
| SUPT1 | Apoptosis Assay | 50 μM | 24/48 h | enhances TRAIL-induces cell apoptosis | 19564891 |
| Jurkat | Apoptosis Assay | 50 μM | 24/48 h | enhances TRAIL-induces cell apoptosis | 19564891 |
| SUPT1 | Growth Inhibition Assay | 50 μM | 24/48/72 h | enhances TRAIL-induces cell growth inhibition | 19564891 |
| Jurkat | Growth Inhibition Assay | 50 μM | 24/48/72 h | enhances TRAIL-induces cell growth inhibition | 19564891 |
| PA-1 | Function Assay | 10 uM | 1 h | inhibits LPA-induced ovarian cancer cell motility | 19647363 |
| OVCAR-3 | Function Assay | 10 uM | 1 h | inhibits LPA-induced ovarian cancer cell motility | 19647363 |
| PA-1 | Function Assay | 10 uM | 1 h | inhibits LPA-induced STAT3 phosphorylation | 19647363 |
| OVCAR-3 | Function Assay | 10 uM | 1 h | inhibits LPA-induced STAT3 phosphorylation | 19647363 |
| A549 | Function Assay | 15 μm | 1 h | inhibits the phosphorylation of STAT1 on tyrosine 701 was detected 15 min after SPE B treatment | 19801665 |
| BMMC | Function Assay | 0-10 μM | 15 min | inhibits LTC4 release in a dose-dependent fashion with near complete inhibition at concentrations ⩾10 μM | 19835845 |
| THP1 | Function Assay | 10 uM | 30 min | inhibits STAT3 tyrosine phosphorylation by over 60% | 20393690 |
| SW1990 | Invasion Assay | 20 μM | 24 h | reduces invasion of SW1990 cells | 20482858 |
| SW1990 | Function Assay | 20 μM | 24 h | decreases the intensity of p-Stat3 expression | 20482858 |
| SW1990 | Function Assay | 20 μM | 24 h | decreases the expression of MMP-2 and VEGF mRNAs | 20482858 |
| SW1990 | Growth Inhibition Assay | 20 μM | 24/48/72 h | inhibits cell growth time dependently | 20482858 |
| MZ-304 | Function Assay | 50/100 μM | 48 h | reduces transcription of MMP genes and reduces enzymatic activity of MMPs | 20589525 |
| MZ-256 | Function Assay | 50/100 μM | 48 h | reduces transcription of MMP genes and reduces enzymatic activity of MMPs | 20589525 |
| MZ-54 | Function Assay | 50/100 μM | 48 h | reduces transcription of MMP genes and reduces enzymatic activity of MMPs | 20589525 |
| MZ-18 | Function Assay | 50/100 μM | 48 h | reduces transcription of MMP genes and reduces enzymatic activity of MMPs | 20589525 |
| A-172 | Function Assay | 50/100 μM | 48 h | reduces transcription of MMP genes and reduces enzymatic activity of MMPs | 20589525 |
| MZ-304 | Function Assay | 100 μM | 48 h | inhibits invasion | 20589525 |
| MZ-256 | Function Assay | 100 μM | 48 h | inhibits invasion | 20589525 |
| MZ-54 | Function Assay | 100 μM | 48 h | inhibits invasion | 20589525 |
| MZ-18 | Function Assay | 100 μM | 48 h | inhibits invasion | 20589525 |
| A-172 | Function Assay | 100 μM | 48 h | inhibits invasion | 20589525 |
| MZ-304 | Function Assay | 50/100 μM | 48 h | inhibits migration | 20589525 |
| MZ-256 | Function Assay | 50/100 μM | 48 h | inhibits migration | 20589525 |
| MZ-54 | Function Assay | 50/100 μM | 48 h | inhibits migration | 20589525 |
| MZ-18 | Function Assay | 50/100 μM | 48 h | inhibits migration | 20589525 |
| A-172 | Function Assay | 50/100 μM | 48 h | inhibits migration | 20589525 |
| 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 | 20589525 |
| 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 | 20589525 |
| 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 | 20589525 |
| 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 | 20589525 |
| 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 | 20589525 |
| MZ-304 | Function Assay | 50/100 μM | 48 h | reduces the levels of constitutively activated STAT3 in a time-dependent and dose-dependent fashion | 20589525 |
| MZ-256 | Function Assay | 50/100 μM | 48 h | reduces the levels of constitutively activated STAT3 in a time-dependent and dose-dependent fashion | 20589525 |
| MZ-54 | Function Assay | 50/100 μM | 48 h | reduces the levels of constitutively activated STAT3 in a time-dependent and dose-dependent fashion | 20589525 |
| MZ-18 | Function Assay | 50/100 μM | 48 h | reduces the levels of constitutively activated STAT3 in a time-dependent and dose-dependent fashion | 20589525 |
| A-172 | Function Assay | 50/100 μM | 48 h | reduces the levels of constitutively activated STAT3 in a time-dependent and dose-dependent fashion | 20589525 |
| HEL | Growth Inhibition Assay | 100 μM | 0-5 d | reduces growth of JAK2V617F-expressing HEL cells | 20621061 |
| HEL | Function Assay | 100 μM | 12-72 h | inhibits the level of p-JAK2, JAK2 | 20621061 |
| KF8 | Function Assay | 10 μM | 1 h | inhibits IL-33-induced IκBα degradation and NF-κB activation | 20940045 |
| KF8 | Function Assay | 10 μM | 1 h | inhibits IL-33-induced NF-κB activation | 20940045 |
| Hep-2 | Function Assay | 50 μM | 24/48/72 h | downregulates the STAT3, p-STAT3 and survivin protein levels | 21309481 |
| Hep-2 | Function Assay | 50 μM | 24/48/72 h | inhibits G1 to S cell cycle transition and induces G1 cell cycle arrest | 21309481 |
| Hep-2 | Apoptosis Assay | 50 μM | 24/48/72 h | induces cell apoptosis time dependently | 21309481 |
| Hep-2 | Growth Inhibition Assay | 25-100 μM | 24/48/72 h | inhibits cell growth in both time and dose dependent manner | 21309481 |
| HSC-T6 | Function Assay | 10 μM | 2 h | inhibits the expressions of pY-STAT1 and Bad induced by CDE | 21396998 |
| HSC-T6 | Apoptosis Assay | 10 μM | 2 h | inhibits the apoptosis of HSC-T6 cells induced by CDE | 21396998 |
| ARPE-19 | Function Assay | 5 μM | 30 min | inhibits JAK2 phosphorilation | 21620963 |
| HT29 | Function Assay | 100 µM | 24/48/72 h | decreases the pSTAT3 levels in a time-dependent manner | 22050790 |
| SW1116 | Function Assay | 100 µM | 24/48/72 h | decreases the pSTAT3 levels in a time-dependent manner | 22050790 |
| HT29 | Function Assay | 100 µM | 24/48/72 h | decreases the expression of JAK2 and pJAK2 time-dependently | 22050790 |
| SW1116 | Function Assay | 100 µM | 24/48/72 h | decreases the expression of JAK2 and pJAK2 time-dependently | 22050790 |
| RPE | Function Assay | 30 µM | 3 h | inhibits the induction of p-STAT3 expression | 23094067 |
| SW620 | Function Assay | 20 µM | 1/6 h | inhibits p-STAT3 activation | 23110625 |
| NRK-52E | Function Assay | 5 μM | 30 min | attenuates Ang-(1–7)-inhibited TGF-β1 mRNA at 16 h | 23174757 |
| BV-2 | Function Assay | 20 µM | 16 h | inhibits LPS-induced STAT1 phosphorylation with almost completely diminished iNOS expression | 23236370 |
| HUVECs | Apoptosis Assay | 20 µM | 4 h | significantly decreases the cell apoptotic index | 23483946 |
| HUVECs | Cell Viability Assay | 20 µM | 4 h | attenuates H2O2-induced cell shrinkage and improved the attachment rate of the cells | 23483946 |
| A549 | Function Assay | 10/20/40 μM | 24 h | suppresses the radiation-induced elevation of VEGF | 23620191 |
| A549 | Function Assay | 20/40 μM | 20 h | 20 μM AG490 suppresses the radiation-induced invasion of A549 cells | 23620191 |
| RAW264.7 | Function Assay | 50 μM | 24/48 h | inhibits RANKL-induced NFATc1 expression and phosphorylation of Ser727STAT3 | 23665018 |
| 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 | 23665018 |
| RAW264.7 | Growth Inhibition Assay | 0-50 μM | 48 h | inhibits cell growth dose-dependently | 23665018 |
| RAW264.7 | Function Assay | 50 μM | 24/48 h | suppresses RANKL-induced osteoclastogenesis | 23665018 |
| HepG2 | Function Assay | 100 μM | 12/24 h | inhibits STAT3 tyrosine phosphorylation | 23836400 |
| 7TD1-WD-90 | Function Assay | 50 μM | 6 h | significantly inhibits the phosphorylation of JAK2 and phosphorylation of STAT3 | 23871159 |
| 7TD1-WD-90 | Apoptosis Assay | 50 μM | 48 h | induces apoptosis | 23871159 |
| 7TD1-DXM | Apoptosis Assay | 50 μM | 48 h | induces apoptosis | 23871159 |
| 7TD1-WD-90 | Growth Inhibition Assay | 10 μM | 72 h | inhibits cell growth | 23871159 |
| 7TD1-DXM | Growth Inhibition Assay | 10 μM | 72 h | inhibits cell growth | 23871159 |
| MC3T3-E1 | Function Assay | 50 μM | 4 h | inhibits HSE-induced BMP7 and GHR protein expression | 23877734 |
| 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 | 24151255 |
| 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 | 24151255 |
| AGS | Function Assay | 50 μM | 24/48/72 h | the levels of pJAK2 began to decline at 24 hr, and rebounded at 72 hr | 24151255 |
| SGC7901 | Function Assay | 50 μM | 24/48/72 h | the levels of pJAK2 began to decline at 24 hr, and rebounded at 72 hr | 24151255 |
| AGS | Cell Viability Assay | 0-100 μM | 24/48/72 h | causes a significant reduction in cell viability dose-dependently but not time-dependently | 24151255 |
| SGC7901 | Cell Viability Assay | 0-100 μM | 24/48/72 h | causes a significant reduction in cell viability dose-dependently but not time-dependently | 24151255 |
| 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 | 24242046 |
| EJ | Function Assay | 50/80 μM | 48 h | downregulates c-Myc, cyclinD1, survivin and VEGF expressions | 24587049 |
| EJ | Growth Inhibition Assay | 50/80 μM | 48 h | causes S-phase arrest | 24587049 |
| EJ | Growth Inhibition Assay | 50/80 μM | 24/48/72 h | inhibits cell growth in both time and dose dependent manner | 24587049 |
| HSC | Function Assay | 20 μM | 1 h | abrogates the differential effects of leptin or AGEs | 24614199 |
| NRK-52E | Function Assay | 1 µM | 10 min | blocks Ang II induced CD24 expression | 24710423 |
| NRK-52E | Function Assay | 1 µM | 10 min | blocks the stimulatory effect of Ang II on Pax-2 expression | 24710423 |
| GL37 | Cell Viability Assay | 0-10 µM | 48 h | suppresses La expression | 24999657 |
| TRPM2/HEK | Function Assay | 10 µM | 40 min | reduces TRPM2 activation even at high concentrations of H2O2 | 25179574 |
| 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 | 25179574 |
| 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 | 25179574 |
| B16-F0 | Function Assay | 50/100 µM | 48 h | reduces anoikis resistance | 25216522 |
| SK-MEL-2 | Function Assay | 50/100 µM | 48 h | reduces anoikis resistance | 25216522 |
| SK-MEL-5 | Function Assay | 50/100 µM | 48 h | reduces anoikis resistance | 25216522 |
| MeWo | Function Assay | 50/100 µM | 48 h | reduces anoikis resistance | 25216522 |
| SK-MEL-28 | Function Assay | 50/100 µM | 48 h | reduces anoikis resistance | 25216522 |
| BCBL1 | Function Assay | 100 µM | 24 h | induces a complete autophagic flux | 26184999 |
| BC3 | Function Assay | 100 µM | 24 h | induces a complete autophagic flux | 26184999 |
| BCBL1 | Function Assay | 100 µM | 24 h | mediates de-phosphorylation of STAT3 correlated with HSP70 and HSF2 reduction | 26184999 |
| BC3 | Function Assay | 100 µM | 24 h | mediates de-phosphorylation of STAT3 correlated with HSP70 and HSF1 reduction | 26184999 |
| BCBL1 | Function Assay | 100 µM | 24 h | mediates PEL cell apoptosis | 26184999 |
| BC3 | Function Assay | 100 µM | 24 h | mediates PEL cell apoptosis | 26184999 |
| 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 |
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| 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] |
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|---|---|---|---|---|
| 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。 |
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| 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] |
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| 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 | |
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) | |||
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体外溶解度 |
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 |
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体内溶解度 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
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
只
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，注：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：取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：取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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