AZD7762

製品コード：S1532 純度：99.99%

AZD7762 is a potent and selective inhibitor of Chk1 with IC50 of 5 nM in a cell-free assay. It is equally potent against Chk2 and less potent against CAM, Yes, Fyn, Lyn, Hck and Lck. Phase 1.

CAS No. 860352-01-8

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 28800	国内在庫あり
2mg	JPY 22000	国内在庫あり
5mg	JPY 37000	国内在庫あり
25mg	JPY 88500	国内在庫あり
1g	JPY 448500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：sales@selleck.co.jp よく尋ねられる質問

文献中Selleckの製品使用例（130）

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製品安全説明書

現在のバッチを見る：純度： 99.99%

99.99

AZD7762関連製品

関連ターゲット	Chk1 Chk2	もっと見る
関連製品	Rabusertib (LY2603618) MK-8776 (SCH 900776) CHIR-124 Prexasertib HCl (LY2606368) PF-477736 BML-277 (Chk2 Inhibitor II) Prexasertib (LY2606368) CCT245737 (SRA737) GDC-0575	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library MAPK Inhibitor Library DNA Damage/DNA Repair compound Library Cell Cycle compound library	もっと見る

シグナル伝達経路

Chkシグナル伝達経路

Chk阻害剤の選択性比較

阻害剤	Citation	Chk1	Chk2	その他
AZD7762	130	+++
Rabusertib (LY2603618)	95	+++
MK-8776 (SCH 900776)	75	+++		CDK2
CHIR-124	45	++++		FLT3,PDGFR,GSK-3
PF-477736	34	++++	+	VEGFR2,Fms,YES
CCT241533 hydrochloride	0		++++
Prexasertib (LY2606368)	19	++++	++	RSK1
VX-803 (M4344)	7	++		ATR
DB07268	0	+		JNK1
GDC-0575	5	+++
BML-277 (Chk2 Inhibitor II)	15		+
CCT245737 (SRA737)	9	+++
SAR-020106	0	++
PD0166285	7	+		Wee1,Myt1
Prexasertib HCl (LY2606368)	43	++++	++	RSK
LY2880070	0	✔

1. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation. 2. "✔" indicates inhibitory effect, but without specific value.

Cell Data

Cell Lines	Assay Type	活性情報	PMID
EW-16	Growth Inhibition Assay	IC50=0.53774 μM	SANGER
NB13	Growth Inhibition Assay	IC50=0.53657 μM	SANGER
SNU-423	Growth Inhibition Assay	IC50=0.53466 μM	SANGER
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

AZD7762 is a potent and selective inhibitor of Chk1 with IC50 of 5 nM in a cell-free assay. It is equally potent against Chk2 and less potent against CAM, Yes, Fyn, Lyn, Hck and Lck. Phase 1.

Targets

Chk1 ^[1] (Cell-free assay)	Chk2 ^[1] (Cell-free assay)
5 nM	<10 nM

In Vitro
In vitro	AZD7762, a more selective Chk1 inhibitor, inhibits Chk1 phosphorylation of a cdc25C peptide by reversibly binding to the ATP-binding site of Chk1, with IC50 of 5 nM and K_i of 3.6 nM. AZD7762 induces cell arrest with EC50 of 0.620 μM, and significantly abrogates the camptothecin induced G2 arrest with an EC50 of 10 nM, by blocking the chk1 dependent degradation of Cdc25A and activation of Cyclin A. AZD7762 (300 nM) enhances the antitumor efficacy of against SW620 and against MDA-MB-231 by reducing the GI50 values from 24.1 nM and 2.25 μM to 1.08 nM and 0.15 μM, respectively. ^[1] AZD7762 shows cytotoxicity against a variety of neuroblastoma cell lines bearing p53 wild type, p53 mutation, Mdm2 amplification or p14 deletion with IC50 values ranging from 82.6-505.9 nM. ^[2]
Kinase Assay	Chk1 Kinase Assay
Kinase Assay	Recombinant human Chk1 is expressed as a S-transferase fusion in insect cells using a baculovirus vector and purified by affinity chromatography. A synthetic peptide substrate (N-biotinylaminohexanoyl-KKVSRSGLYRSPMPENLNRPR) for Chk1 is synthesized. Final assay concentrations of peptide and ATP (cold + 40 nCi [³³P]ATP) are 0.8 and 1 μM, respectively. Different concentrations of AZD7762, buffer containing peptide and chk1 kinase and ATP, are added sequentially to a 384-well assay plate. The plate is incubated for 2 hours, reaction is stopped by the addition of buffer containing EDTA and scintillation proximity assay beads, and plates are read using a TopCount reader. Data analysis is carried out to determinate a dose response (IC50).
細胞実験	細胞株	HT29, SW620 and MDA-MB-231 cells
	濃度	Dissolved in DMSO, final concentration ~12.5 μM
	反応時間	20 or 48 hours
	実験の流れ	For the checkpoint abrogation assay, HT29 cells are treated for 2 hours with camptothecin (topoisomerase I inhibitor; 0.07 μg/mL) to induce the G2 checkpoint. Cells are then treated for 20 hours with a 12-point titration of AZD7762 (12.5 μM to 6 nM) plus nocodazole. Cells are fixed with 3.7% formaldehyde for 1 hour, permeabilized with PBS containing 0.05% Triton X, and incubated with anti-phH3 antibody for 1 hour followed by Alexa Fluor 488 anti-rabbit and Hoechst stain for 1 hour. Mitotic index is determined on the ArrayScan and expressed as the percentage of cells undergoing mitosis. For the potentiation assays, SW620 or MDA-MB-231 cells are dosed for 24 hours with a 9-point titration of ranging from 0.01 to 100 nM with a constant dose of AZD7762 (300 nM). After 24 hours, medium is removed and AZD7762 alone is added back to the wells for an additional 24 hours. Cells are then incubated in AZD7762-free medium for an additional 72 hours. The effect on cell proliferation is determined by MTT.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	pChk1 / Chk1 / Wee1 / p21 / p53		29963769
	Growth inhibition assay	Cell viability		23715154

In Vivo
In Vivo	AZD7762 alone at 25 mg/kg shows little antitumor activity in the H460-DNp53 xenograft mice and SW620 xenograft mice, but when administrated in combination, AZD7762 shows significant antitumor efficacy in the two xenografts mice with a log cell kill of 0.9 or percent treated/control (%T/C) of 26 even at low dose of 12.5 mg. Dosing of AZD7762 in combination in the H460-DNp53 xenograft rat inhibits the tumor volume in a dose-dependent manner with the %T/C values of 48 and 32 for 10 and 20 mg/kg AZD7762, respectively. AZD7762 (25 mg/kg) in combination causes complete tumor regression in the SW620 xenograft mice with the %T/C increasing significantly to -66% and -67%, respectively. ^[1]
動物実験	動物モデル	Male NCr mice implanted s.c. with H460-DNp53 cells or SW620, and male rnu rats implanted s.c. with H460-DNp53 cells
	投与量	~25 mg/kg
	投与経路	Injection i.v.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT00937664	Terminated	Cancer\|Solid Tumors\|Advanced Solid Malignancies	AstraZeneca	July 2009	Phase 1
NCT00473616	Terminated	Advanced Solid Tumors\|Cancer\|Advanced Solid Malignancies	AstraZeneca	May 2007	Phase 1
NCT00413686	Completed	Solid Tumors	AstraZeneca	December 2006	Phase 1

参考
[1] Zabludoff SD, et al. Mol Cancer Ther, 2008, 7(9), 2955-2966.

参考

[1] Zabludoff SD, et al. Mol Cancer Ther, 2008, 7(9), 2955-2966.

化学情報

分子量	362.42	化学式	C₁₇H₁₉FN₄O₂S
CAS No.	860352-01-8	SDF	Download AZD7762 SDFをダウンロードする
Smiles	C1CC(CNC1)NC(=O)C2=C(C=C(S2)C3=CC(=CC=C3)F)NC(=O)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ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 73 mg/mL ( (201.42 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

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よくある質問（FAQ）

質問1:
If I want to use the inhibitor for i.p. injection, can I use DMSO to dissolve it?

回答
Since DMSO has low toxicity with i.p. injection, hydroxyproplyl-β-cyclodextrin is consider a safer co-solvent in compound formulation. In a previous literature report, 11.3% hydroxyproplyl-β-cyclodextrin was used to formulate this compound for i.v. injection.

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