AG-490

别名: Tyrphostin B42, Zinc02557947

目录号：S1143

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

规格	价格	库存
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
更大包装有超大折扣
400-668-6834 info@selleck.cn

产品质控

AG-490相关产品

相关靶点	EGFR/ErbB1 HER2/ErbB2 ErbB3 ErbB4 mutant EGFR	点击展开
相关产品	AG-1478 Canertinib (CI-1033) Rociletinib (CO-1686) WZ4002 Genistein Poziotinib PD153035 PD153035 HCl Allitinib tosylate AEE788 (NVP-AEE788) Pelitinib (EKB-569) Canertinib dihydrochloride Varlitinib Icotinib (BPI-2009H) Nazartinib (EGF816) NSC228155 PD168393 Olmutinib (BI 1482694) Zorifertinib (AZD3759) AZ5104 Lazertinib CL-387785 (EKI-785) TAK-285 Daphnetin Pyrotinib dimaleate Alflutinib (Furmonertinib) mesylate EGFR Inhibitor Chrysophanic Acid Norcantharidin WZ8040 Butein Cyasterone Avitinib (Abivertinib) CNX-2006 MTX-211 Naquotinib(ASP8273) Tuxobertinib (BDTX-189) WZ3146 (S)-Sunvozertinib ((S)-DZD9008) Tyrphostin 9 EAI045 zipalertinib (TAS6417) Almonertinib (HS-10296) AG-18	点击展开
相关化合物库	激酶抑制剂库酪氨酸激酶抑制剂分子库 PI3K/Akt 抑制剂库细胞周期化合物库血管生成相关化合物库	点击展开

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	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

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Stat3^sm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
激酶实验	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 4^oC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4^oC 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

参考文献
http://www.ncbi.nlm.nih.gov/pubmed/1676428 http://www.ncbi.nlm.nih.gov/pubmed/8628398 http://www.ncbi.nlm.nih.gov/pubmed/9192639 http://www.ncbi.nlm.nih.gov/pubmed/10380915 http://www.ncbi.nlm.nih.gov/pubmed/11264165 http://www.ncbi.nlm.nih.gov/pubmed/12481410 http://www.ncbi.nlm.nih.gov/pubmed/16818614 http://www.ncbi.nlm.nih.gov/pubmed/19327411 + 展开

参考文献

http://www.ncbi.nlm.nih.gov/pubmed/1676428
http://www.ncbi.nlm.nih.gov/pubmed/8628398
http://www.ncbi.nlm.nih.gov/pubmed/9192639

http://www.ncbi.nlm.nih.gov/pubmed/10380915
http://www.ncbi.nlm.nih.gov/pubmed/11264165
http://www.ncbi.nlm.nih.gov/pubmed/12481410
http://www.ncbi.nlm.nih.gov/pubmed/16818614
http://www.ncbi.nlm.nih.gov/pubmed/19327411

+ 展开

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)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1年-80°C溶于溶剂
储存条件(自收到货起)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1个月-20°C溶于溶剂

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
=	×	×

稀释计算器分子量计算器

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）

给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 μL 动物数量只

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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操作手册

如果有其他问题，请给我们留言。

* 必填项

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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