AZ20

製品コード：S7050 純度：99.92%

AZ20 is a novel potent and selective inhibitor of ATR kinase with IC50 of 5 nM in a cell-free assay, 8-fold selectivity over mTOR.

CAS No. 1233339-22-4

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 40500	国内在庫あり
5mg	JPY 29500	国内在庫あり
25mg	JPY 85500	国内在庫あり
1g	JPY 598500	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（44）

製品安全説明書

現在のバッチを見る： S705001 DMSO] 83 mg/mL] false] Ethanol] 3 mg/mL] false] Water] Insoluble] false 純度： 99.92%

99.92

AZ20関連製品

関連ターゲット	ATM ATR	もっと見る
関連製品	KU-55933 VE-821 Chloroquine diphosphate KU-60019 Berzosertib (VE-822) Ceralasertib (AZD6738) AZD0156 Mirin AZD1390 CP-466722 Elimusertib (BAY-1895344) hydrochloride ETP-46464 Elimusertib (BAY-1895344) CGK 733 VX-803 (M4344) AZ31 AZ32 HAMNO	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library Apoptosis Compound Library Cell Cycle compound library NF-κB Signaling Compound Library	もっと見る

シグナル伝達経路

ATM/ATRシグナル伝達経路

ATM/ATR阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
LoVo	Antitumor assay	50 mg/kg	13 days	Antitumor activity against human LoVo cells xenografted in Swiss nu/nu mouse assessed as tumor growth inhibition at 50 mg/kg, po qd for 13 days relative to control	23394205
LoVo	Antitumor assay	25 mg/kg	13 days	Antitumor activity against human LoVo cells xenografted in Swiss nu/nu mouse assessed as tumor growth inhibition at 25 mg/kg, po bid for 13 days relative to control	23394205
LoVo	Function assay	25 mg/kg	8 hrs	Plasma concentration in Swiss nu/nu mouse xenografted with human LoVo cells at 25 mg/kg, po bid after 8 hrs, Cp=1.8μM	30346772
LoVo	Function assay	50 mg/kg	8 hrs	Plasma concentration in Swiss nu/nu mouse xenografted with human LoVo cells at 50 mg/kg, po qd after 8 hrs, Cp=3.5μM	30346772
LoVo	Growth inhibition assay		72 hrs	Growth inhibition of human LoVo cells after 72 hrs by MTS assay, GI50=0.2μM	23394205
HT29	Function assay		1 hr	Inhibition of ATR-mediated CHK1 phosphorylation at serine 345 in human HT29 cells after 1 hr in presence of 4-nitroquinoline 1-oxide, IC50=0.05μM	23394205
HT29	Function assay		60 mins	Inhibition of ATR in human HT29 cells after 60 mins by Hoechst 33258 staining-based assay, IC50=0.061μM	30346772
LoVo	Cytotoxicity assay		72 hrs	Cytotoxicity against human LoVo cells after 72 hrs by MTS assay, GI50=0.2μM	30346772
HT-29	Cytotoxicity assay		72 hrs	Cytotoxicity against human HT-29 cells after 72 hrs by MTS assay, GI50=0.97μM	30346772
MDA-MB-468	Function assay			Inhibition of mTOR-mediated AKT phosphorylation at serine 473 in human MDA-MB-468 cells, IC50=2.4μM	23394205
MDA-MB-468	Function assay			Inhibition of mTOR in human MDA-MB-468 cells assessed as decrease in 70S6K S235/236 phosphorylation, IC50=0.72μM	30346772
MDA-MB-468	Function assay			Inhibition of mTOR in human MDA-MB-468 cells assessed as decrease in AKT phosphorylation at S473 residue, IC50=2.4μM	30346772
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生物活性

製品説明

AZ20 is a novel potent and selective inhibitor of ATR kinase with IC50 of 5 nM in a cell-free assay, 8-fold selectivity over mTOR.

特性

ATR-selective inhibitor with high permeability and good stability.

Targets

ATR ^[2] (Cell-free assay)	mTOR ^[2] (Cell-free assay)
5 nM	38 nM

In Vitro
In vitro	AZ20 shows good selectivity against all of the PI3K isoforms together with ATM and DNA-PK. ^[2] In vitro, AZ20 decreases pChk1 Ser345, pChk1 Ser317 and pChk1 Ser296 levels in a concentration-dependent manner. Prolonged exposure with AZ20 increases γH2AX pan-nuclear staining, indicative of replication stress. This is associated with S-phase arrest and increase in phospho-histone H3. AZ20 induces growth inhibition and cell death in vitro and its profile of activity is distinct from other cytotoxic agents. The cytotoxic effect of AZ20 can be increased in combination with the selective ATM inhibitor KU-60019. ^[1]
実験結果図	Methods	Biomarkers	結果図	PMID
	Growth inhibition assay	IC50		28176818
	Western blot	p-CDK1 / CDK1 / p-CDK2 / CDK2 γH2AX / RRM1 / RRM2		28176818

In Vivo
In Vivo	Female nude mice bearing LoVo tumors are treated with AZ20 orally at a dose of 25 mg/kg twice daily or 50 mg/kg once daily for 13 days, led to significant tumor growth inhibition. ^[2] This is associated with a persistent elevation of γH2AX pan-nuclear staining in xenograft tissue, but a transient increase in mouse bone marrow at therapeutic doses, suggesting a favourable therapeutic index. ^[1] AZ20 is assessed for drug−drug interaction (DDI) potential specifically from inhibition of cytochrome P450 enzymes. AZ20 is found to inhibit the cytochrome 3A4-mediated metabolism of midazolam by 50% at 10 μM. AZ20 has respectable bioavailability in a low dose rat PK study. ^[2]
動物実験	動物モデル	LoVo colorectal adenocarcinoma xenografts
	投与量	25 mg/kg twice daily and 50 mg/kg once daily
	投与経路	orally

参考
[1] Xavier Jacq, et al. Cancer Res 2012;72(8 Suppl):Abstract nr 1823. [2] Foote KM, et al. J Med Chem, 2013, 56(5), 2125-2138.

参考

化学情報

分子量	412.51	化学式	C₂₁H₂₄N₄O₃S
CAS No.	1233339-22-4	SDF	Download AZ20 SDFをダウンロードする
Smiles	CC1COCCN1C2=NC(=NC(=C2)C3(CC3)S(=O)(=O)C)C4=C5C=CNC5=CC=C4
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 : 83 mg/mL ( (201.2 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 : 3 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。

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

* 必須

よくある質問（FAQ）

質問1:
If I want to completely block the kinase activity from the in vitro cell lines, how much concentration I should use?

回答
IC50 5nM was quoted from a previous publication in which the author tested IC50 of AZ20 in cell free assay. In cell culture, many factors, such as membrane permeability and target protein concentration, may affect the efficiency. Each cell line responses to the same compound differently and it is very difficult to predict the optimized concentration simply based on cell free data. In cell culture experiment, the required concentration is usually higher. We recommend that you perform a pilot experiment and test different concentrations (50nM to 500uM) to get the optimized condition.

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):