AG-490

AG-490 is an inhibitor of EGFR with IC50 of 0.1 μM in cell-free assays, 135-fold more selective for EGFR versus ErbB2, also inhibits JAK2 with no activity to Lck, Lyn, Btk, Syk and Src.

CAS No. 133550-30-8

サイズ	価格(税別)	在庫状況
10mg	JPY 13300	国内在庫あり
25mg	JPY 18600	国内在庫あり
50mg	JPY 27500	国内在庫あり

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（125）

製品安全説明書

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AG-490関連製品

関連ターゲット	EGFR/ErbB1 HER2/ErbB2 ErbB3 ErbB4 mutant EGFR	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Cell Cycle compound library Angiogenesis Related compound Library	もっと見る

シグナル伝達経路

EGFRシグナル伝達経路

EGFR阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	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
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生物活性

製品説明

AG-490 is an inhibitor of EGFR with IC50 of 0.1 μM in cell-free assays, 135-fold more selective for EGFR versus ErbB2, also inhibits JAK2 with no activity to Lck, Lyn, Btk, Syk and Src.

Targets

JAK2 (V617F) ^[8]	EGFR ^[1] (Cell-free assay)
	0.1 μM

In Vitro
In vitro	AG-490 inhibits HER-2 driven cell proliferation with IC50 of 3.5 μM. ^[1] Corresponding to the specific dose-dependent inhibition of constitutively activated JAK2 in pre-B acute leukemia (ALL) cells, AG-490 (5 μM) almost completely blocks the growth of all ALL cells by inducing programmed cell death, with no deleterious effect on normal hematopoiesis. AG-490 does not inhibit the activities of Lck, Lyn, Btk, Syk, and Src. ^[2] AG-490 (60-100 μM) blocks the constitutive activation of Stat3sm, and inhibits spontaneous as well as interleukin 2-induced growth of mycosis fungoides (MF) tumor cells with IC50 values of 75 μM and 20 μM, respectively. ^[3] AG-490 potently inhibits IL-2-mediated human T cell growth with an IC50 of 25 μM by blocking the activities of JAK3 and STAT5a/b. ^[4] Although AG-490 alone has no effect on proliferation of FDrv210H cells at a concentration of 5 μM, AG-490 can synergize with STI571 to enhance its inhibitory effect on p210^bcr-abl driven proliferation. ^[5] AG-490 significantly inhibits the constitutive activation of Stat3 in MOPC, MPC11, and S194 cells, leading to dramatic dose-dependent apoptosis. ^[6] AG-490 (100 μM) inhibits Akt phosphorylation, inhibits the activation of nuclear factor-κB, and causes the activation of GSK-3β, leading to the reduction of c-Myc. AG-490 (50 μM) can induce apoptosis of imatinib-resistant BaF3 cells expressing T315I and E255K mutants of Bcr-Abl. ^[7] AG-490 at 30 μM inhibits not only Epo-induced phosphorylation of wild-type JAK2 but also constitutive phosphorylation of the JAK2 V617F mutant. AG-490 also potently inhibits cytokine-independent cell growth induced by the JAK2 V617F mutant in BaF3 cells. ^[8]
Kinase Assay	In vitro kinase autophosphorylation
Kinase Assay	AG-490 is dissolved in DMSO 10%-H₂O-ethanol 45%. Crude membrane extracts (0.125 μg/mL) are preactivated with EGF (20 nM) in 50 mM HEPES buffer, pH 7.6, and 125 mM NaCl, for 15 minutes at 4 °C. Autophosphorylation activity of EGFR or ErbB2 kinase is assayed at 4 °C for 30 seconds in V-shaped 96-well plates. Membrane extracts (8 μL) are added to each well containing reaction mixture (12 μL, 50mM, HEPES, pH 7.4,125 mM NaCl, 12 mM M₈Ac₂, 2 mM MnCl₂, 1 mM NaVO₃, 1 μM ATP, and 1 μCi[γ-³²P]ATP, final concentrations) and increasing concentrations of AG-490 (4 μL). After termination by addition of hot sample buffer, the samples are run on a 6% SDS-polyacrylamide gel electrophoresis minigel, the gels dried, and autoradiography performed during the linear exposure time period. The receptor bands are scanned densitrometrically, and the results analyzed by the Ez-Fit program. For the analysis of autophosphorylation of JAK2, JAK2 is immunoprecipitated by using anti-JAK2 antibody from lysates of G2 cells pretreated for 16 hours with increasing concentrations of AG-490 (0-50 μM). Immune complexes are then immunoblotted with anti-phosphotyrosine antibody. A dose-dependent inhibition of in vitro kinase activity is demonstrated by assessing JAK2 autophosphorylation.
細胞実験	細胞株	Pre-B ALL
	濃度	Dissolved in DMSO, final concentrations ~ 50 μM
	反応時間	16 hours
	実験の流れ	Cells are exposed to different concentrations of AG-490 for 16 hours. For the determination of cell proliferation, [³H]tymidine (1 μCi) is added 6 hours or more before the cultures are terminated. Cells are then collected and samples counted in a liquid scintillation counter.

In Vivo
In Vivo	Administration of AG-490 drastically reduces the numbers of CD45⁺ and HLA-DR⁺ cells from 48 % and 46% in bone marrow of untreated mice, as well as 38% and 22% in the spleen of untreated mice to undetectale levels. ^[2] In vivo administration of AG-490 causes murine myeloma tumor cell apoptosis but does not inhibit IL-12-mediated macrophage activation and IFN-γ production by lymphocytes. ^[6] Consistent with the in vitro blocking of JAK2 V617F mutant activity, AG-490 treatment at 0.5 mg/day for 10 days effectively inhibits JAK2 V617F mutant-induced tumorigenesis and tumor cell invasion in nude mice. ^[8] Combined therapy with AG-490 and IL-12 induces greater antitumor effects than either agent alone in a murine myeloma tumor model. ^[6]
動物実験	動物モデル	SCID mice intravenously injected with ALL cells
	投与量	0.85 mg + 0.5 mg daily
	投与経路	Continuous pump infusion supplemented with daily intraperitoneal injections

参考
[1] Gazit A, et al. J Med Chem, 1991, 34(6), 1896-1907. [2] Meydan N, et al. Nature, 1996, 379(6566), 645-648. [3] Nielsen M, et al. Proc Natl Acad Sci U S A, 1997, 94(13), 6764-6769. [4] Kirken RA, et al. J Leukoc Biol, 1999, 65(6), 891-899. [5] Sun X, et al. Blood, 2001, 97(7), 2008-2015. [6] Burdelya L, et al. Mol Cancer Ther, 2002, 1(11), 893-899. [7] Samanta AK, et al. Cancer Res, 2006, 66(13), 6468-6472. [8] Abe M, et al. Int Immunopharmacol, 2009, 9(7-8), 870-877. + 展開

参考

+ 展開

化学情報

分子量	294.30	化学式	C₁₇H₁₄N₂O₃
CAS No.	133550-30-8	SDF	Download AG-490 SDFをダウンロードする
Smiles	C1=CC=C(C=C1)CNC(=O)C(=CC2=CC(=C(C=C2)O)O)C#N
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 58 mg/mL ( (197.07 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 9 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):