AG-1478

別名：Tyrphostin AG-1478, NSC 693255

製品コード：S2728 純度：99.92%

AG-1478 is a selective EGFR inhibitor with IC50 of 3 nM in cell-free assays, almost no activity on HER2-Neu, PDGFR, Trk, Bcr-Abl and InsR. AG-1478 (Tyrphostin AG-1478) inhibits encephalomyocarditis virus (EMCV) and hepatitis c virus (HCV) by targeting phosphatidylinositol 4-kinase IIIα (PI4KA).

CAS No. 153436-53-4,175178-82-2

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
5mg	JPY 22000	国内在庫あり
25mg	JPY 55500	国内在庫あり
1g	JPY 388500	国内在庫なし(納期7~10日)

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（96）

製品安全説明書

現在のバッチを見る： S272801 DMSO] 25 mg/mL] false] Ethanol] 13 mg/mL] false] Water] Insoluble] false 純度： 99.92%

99.92

AG-1478関連製品

関連ターゲット	EGFR/ErbB1 HER2/ErbB2 ErbB3 ErbB4 mutant EGFR	もっと見る
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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
A431	Function assay	~10 μM		induces cell cycle arrest	10702262
MDA-468	Kinase assay	~10 μM		inhibits the basal and TGF-α-stimulated tyrosine phosphorylation of the EGFR	10702262
A431	Kinase assay	~10 μM		inhibits the basal and TGF-α-stimulated tyrosine phosphorylation of the EGFR	10702262
HPV 16-immortalized human keratinocytes	Apoptosis assay	~50 μM		induces apoptosis.	9288782
HPV 16-immortalized human keratinocytes	Function assay	~50 μM		induces arrest in the Cell Cycle	9288782
HPV 16-immortalized human keratinocytes	Growth inhibitory assay	~50 μM		inhibits cell growth	9288782
U87MG.wtEGFR.	Kinase assay	~100 μM		inhibits EGFR tyrosine kinase activity	8752145
U87MG.ΔEGFR	Kinase assay	~100 μM		inhibits EGFR tyrosine kinase activity	8752145
U87MG	Kinase assay	~100 μM		inhibits EGFR tyrosine kinase activity	8752145
U87MG.wtEGFR.	Growth inhibitory assay	~100 μM		IC50=48.4 μM	8752145
U87MG.ΔEGFR	Growth inhibitory assay	~100 μM		IC50=8.7 μM	8752145
U87MG	Growth inhibitory assay	~100 μM		IC50=34.6 μM	8752145
MDA-MB-231	Kinase assay	~5 μM		inhibits EGF stimulated phosphorylation of FKHR	11030146
CNE2	Growth inhibitory assay	100 μM		inhibits cell proliferation by 98.4%	11410322
CNE2	Kinase assay	~100 μM		inhibits EGFR tyrosine phosphorylation	11410322
CNE2	Function assay	~100 μM		Inhibits MAPK and AKT activation	11410322
CNE2	Function assay	~50 μM		affects cell cycle distribution	11410322
HSC-2	Kinase assay	8 μM		inhibits phosphorylation of EGFR and Akt	17689285
HSC-2	Apoptosis assay	8 μM		inhibits Fas-mediated apoptosis	17689285
HEp-2	Growth inhibitory assay	~10 μM		enhances oridonin-induced growth-inhibitory	20202741
SubG1	Apoptosis assay	~10 μM		enhances oridonin-induced apoptosis	20202741
HEp-2	Function assay	~10 μM		enhances Oridonin-induced Bax activation, Bcl-2 degradation and SIRT1 inactivation	20202741
H508	Growth inhibitory assay	~1 μM		mitigates CPF-mediated H508 cell growth	26514924
HeLa	Function assay		30 mins	Inhibition of EGFR autophosphorylation in human HeLa cells preincubated for 30 mins prior to EGF stimulation by Western blotting	21718029
HEK293	Function assay		1 hr	Inhibition of human full length PKMYT1 expressed in HEK293 cells using EFS (247 to 259 residues) as substrate after 1 hr by fluorescence polarization immunoasay, Ki=1.87μM	29941193
HEK293	Function assay		1 hr	Inhibition of human full length PKMYT1 expressed in HEK293 cells using EFS (247 to 259 residues) as substrate after 1 hr by fluorescence polarization immunoasay, IC50=19.6μM	29941193
A431	Antiproliferative assay			Tested for antiproliferative activity against human A431 cells, IC50=20μM	15109642
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
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生物活性

製品説明

Targets

EGFR ^[1]
(Cell-free assay)

3 nM

In Vitro
In vitro	AG-1478 is high selective over ErbB2 and PDGFR with IC50 of >100 μM. ^[1] AG-1478 preferentially inhibits U87MG cells expressing truncated EGFR with IC50 of 8.7 μM, compared to those expressing endogenous wt EGFR or overexpressing exogenous wt EGFR with IC50 of 34.6 μM and 48.4 μM, respectively, and inhibits the DNA synthesis with IC50 of 4.6 μM, 19.67 μM, and 35.2 μM, respectively. AG-1478 also preferentially inhibits the tyrosine kinase activity and autophosphorylation of the ΔEGFR compared to endogenous or overexpressed exogenous wt EGFR. ^[2] AG-1478 (0.25 μM) abolishes the MAPK activation induced by Ang II, a Ca2+ ionophore as well as EGF but not by a phorbol ester or platelet-derived growth factor-BB in the VSMC. ^[3] AG-1478 inhibits EGF-induced mitogenesis of the BaF/ERX and LIM1215 cells with IC50 of 0.07 μM and 0.2 μM, respectively. ^[6] AG1478 is able to inhibit the function of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCG2, with a more pronounced effect on ABCG2. ^[7]
細胞実験	細胞株	U87MG
	濃度	Dissolved in DMSO, final concentrations ~100 μM
	反応時間	72 hours
	実験の流れ	Cells are exposed to different concentrations of AG-1478 for 72 hours in 96-well plates. The effects of AG-1478 on cell growth are examined using an Alamar Blue assay. A 20-μL aliquot of Alamar Blue is added to each well, and its absorbance is determined using a Spectromax Scanning Micro plate Reader. The effects of AG-1478 are expressed as percentage of growth inhibition using untreated cells as the control (0% inhibition). Cellular DNA synthesis is determined using a [³H]thymidine incorporation assay.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	EGFR / Neu / p-Tyr Shc / PLC-γ1		10931950
	Growth inhibition assay	Cell viability		25258648

In Vivo
In Vivo	Administration of AG-1478 blocks phosphorylation of the EGFR at the tumor site and inhibits the growth of A431 xenografts that overexpress the WT EGFR and glioma xenografts expressing the de2-7 EGFR. Even subtherapeutic doses of AG-1478 significantly enhance the efficacy of cytotoxic drugs, with the combination of AG-1478 displaying synergistic antitumor activity against human glioma xenografts. The combination of AG-1478 and an anti-EGFR antibody (mAb 806) displays additive and in some cases synergistic, antitumor activity against tumor xenografts overexpressing the EGFR. ^[4] The combination of AG-1478 (0.4 mg) with a single dose of 25 μCi ⁹⁰Y-CHX-A''-DTPA-hu3S193 results in a significant enhancement of efficacy compared with either agent alone. ^[5]
動物実験	動物モデル	Female BALB/c nu/nu mice inoculated s.c. with A431 or U87MG.Δ2-7 tumor cells
	投与量	~1 mg/kg
	投与経路	Injection i.p. three times per week

参考
[1] Levitzki A, et al. Science, 1995, 267(5205), 1782-1788. [2] Han Y, et al. Cancer Res, 1996, 56(17), 3859-3861. [3] Eguchi S, et al. J Biol Chem, 1998, 273(15), 8890-8896. [4] Johns TG, et al. Proc Natl Acad Sci U S A, 2003, 100(26), 15871-15876. [5] Lee FT, et al. Clin Cancer Res, 2005, 11(19 Pt 2), 7080s-7086s. [6] Ellis AG, et al. Biochem Pharmacol, 2006, 71(10), 1422-1434. [7] Shi Z, et al. Biochem Pharmacol, 2009, 77(5), 781-793. [8] Shi Z, et al. Oncol Rep, 2009, 21(2), 483-489. [9] Takai N, et al. Mol Med Report, 2010, 3(3), 479-484. + 展開

参考

+ 展開

化学情報

分子量	315.75	化学式	C₁₆H₁₄ClN₃O₂
CAS No.	153436-53-4,175178-82-2	SDF	Download AG-1478 SDFをダウンロードする
Smiles	COC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=CC=C3)Cl)OC
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 : 25 mg/mL ( (79.17 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 : 13 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。

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