NU7441 (KU-57788)

製品コード：S2638 純度：99.94%

NU7441 (KU-57788) is a highly potent and selective DNA-PK inhibitor with IC50 of 14 nM and also inhibits mTOR and PI3K with IC50 of 1.7 μM and 5 μM in cell-free assays, respectively. It reduces the frequency of NHEJ while increasing the rate of HDR following Cas9-mediated DNA cleavage.

CAS No. 503468-95-9

サイズ	価格(税別)	在庫状況
5mg	JPY 22000	国内在庫あり
50mg	JPY 59500	国内在庫あり
200mg	JPY 145500	国内在庫あり
1g	JPY 295500	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（286）

1/10

製品安全説明書

現在のバッチを見る：純度： 99.94%

99.94

NU7441 (KU-57788)と併用されることが多い化合物

KU-0060648

NU7441 and KU-0060648 reduce the frequency of the non-homologous end joining (NHEJ) pathway while increasing the rate of homology-directed recombination (HDR).

Robert F, et al. Genome Med. 2015 Aug 27;7(1):93.

KU-55933

NU7441 and KU-55933 combination treatment significantly increase X-ray cytotoxicity in MDCK cells.

Koike M, et al. J Vet Med Sci. 2022 Nov; 84(11): 1485–1490.

NU7026

NU7441 and NU7026 are potent DNA-PK inhibitors that inhibit the DSBs repair pathway and enhance the sensitivity of cancer cells to ionizing radiation or chemo-potentiation.

Li LY, et al. Front Pharmacol. 2021 Feb 8;11:629266.

NU7441 (KU-57788)関連製品

関連製品	NU7026 AZD7648 CC-115 Nedisertib (M3814) KU-0060648 YU238259 LTURM34	もっと見る
関連化合物ライブラリー	FDA-approved Drug Library Natural Product Library Apoptosis Compound Library DNA Damage/DNA Repair compound Library Cell Cycle compound library	もっと見る

シグナル伝達経路

DNA-PKシグナル伝達経路

DNA-PK阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
INA-6	Function assay	10 uM	4 hrs	Inhibition of heat shock response in human INA-6 cells assessed as reduction in HSF-1 mediated upregulation of the HSP72 protein expression at 10 uM preincubated for 4 hrs followed by HSP90 inhibitor and HSR inducer NVP-AUY922 addition measured after 4 hr	28453931
INA-6	Function assay	10 uM	4 hrs	Inhibition of heat shock response in human INA-6 cells assessed as reduction in HSF-1 mediated upregulation of the HSP72 mRNA expression at 10 uM preincubated for 4 hrs followed by HSP90 inhibitor and HSR inducer NVP-AUY922 addition measured after 4 hrs b	28453931
INA-6	Function assay	10 uM	4 hrs	Downregulation of NVP-AUY922-induced HSF-1 protein expression in human INA-6 cells at 10 uM preincubated for 4 hrs followed by NVP-AUY922 addition measured after 4 hrs by Western blot method	28453931
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

Targets

DNA-PK ^[1] (Cell-free assay)	mTOR ^[1] (cell-free assay)	PI3K ^[1] (cell-free assay)
14 nM	1.7 μM	5 μM

In Vitro
In vitro	NU7441 increases the persistence of γH2AX foci after ionizing radiation–induced DNA damage. NU7441 (0.5 μM or 1 μM) appreciably increases G2-M accumulation induced by ionizing radiation, and doxorubicin in both SW620 and LoVo cells. ^[2] NU7441 causes persistence of doxorubicin- and ionising radiation-induced DNA double-strand break and also slightly decreases homologous recombination activity DNA-PK-proficient M059-Fus-1 and DNA-PK-deficient M059 J human tumour cells. ^[3] NU7441 inhibits UV-induced RPA p34 hyperphosphorylation in a dose-dependent manner both in cells lacking and cells expressing polymerase η. ^[4] NU7441 increases levels of -induced γH2AX foci and correspondingly decreased -induced cell death in chronic lymphocytic leukemia cells. ^[5] NU7441 also inhibits -induced DNA-PKcs autophosphorylation and repair in chronic lymphocytic leukemia cells. ^[6] It reduces the frequency of NHEJ while increasing the rate of HDR following Cas9-mediated DNA cleavage^[7].
細胞実験	細胞株	SW620, LoVo, V3-YAC and V3 cells
	濃度	0.5 μM or 1 μM
	反応時間	17 hours
	実験の流れ	The effect of NU7441 on cellular survival following exposure to doxorubicin, and ionizing radiation is measured in SW620, LoVo, V3, and V3-YAC cells by clonogenic assays. Briefly, growing cells in six-well plates or 6-cm dishes are exposed to doxorubicin with or without NU7441 (0.5 or 1.0 μM) for 16 hours. For radiosensitization studies, NU7441 is added to the cells 1 hour before irradiation. V3 and V3-YAC cells are exposed to γ-irradiation (3.1 Gy/min ¹³⁷Cesium). SW620 and LoVo are exposed to X-irradiation (2.9 Gy/min at 230 kV, 10 mA) due to the equipment available. After irradiation, the cells are incubated with or without NU7441 for a further 16 hours. Cells are then harvested by trypsinization, counted, and seeded into 10-cm diameter Petri dishes at densities varying from 100 to 10⁵ per dish in drug-free medium for colony formation. Colonies are stained with crystal violet after 10 to 14 days and counted with an automated colony counter. The survival reduction factor (SRF) is calculated as the surviving fraction of cells in the absence of NU7441 divided by the surviving fraction of cells in the presence of NU7441 for any given dose or concentration of cytotoxic agent. The dose modification ratio (DMR90) is calculated as the concentration/dose of cytotoxic agent required to kill 90% of the cells in the absence of NU7441 divided by the concentration/dose of cytotoxic agent required to kill 90% of the cells in the presence of NU7441.
実験結果図	Methods	Biomarkers	結果図	PMID
実験結果図	Western blot	p-DNA-PKcs / DNA-PKcs / p-ATM / ATM / p-ATR / ATR / Ku70 / p-CHK1 / p-CHK2/ p-AKT / RAD51 p-mTOR(Ser2448) / mTOR / p-S6K(Thr389)		29344644

In Vivo
In Vivo	NU7441 intraperitoneally administrated at dose of 10 mg/kg maintains for at least 4 hours shows nontoxic and increases induced tumor growth delay 2-fold in mice bearing SW620 xenografts. ^[2]
動物実験	動物モデル	Female rude mice bearing SW620 xenografts
	投与量	10 mg/kg
	投与経路	Intraperitoneally administrated

参考
[1] Leahy JJ, et al. Bioorg Med Chem Lett, 2004, 14(24), 6083-6087. [2] Zhao Y, et al. Cancer Res, 2006 , 66(10), 5354-5362. [3] Tavecchio M, et al. Cancer Chemother Pharmacol, 2012, 69(1), 155-164. [4] Cruet-Hennequart S, et al. DNA Repair (Amst), 2006, 5(4), 491-504. [5] Willmore E, et al. Clin Cancer Res, 2008, 14(12), 3984-3992. [6] Elliott SL, et al. Br J Haematol, 2011, 152(1), 61-71. [7] Robert F, et al. Genome Med. 2015, 7:93. + 展開

参考

+ 展開

化学情報

分子量	413.49	化学式	C₂₅H₁₉NO₃S
CAS No.	503468-95-9	SDF	Download NU7441 (KU-57788) SDFをダウンロードする
Smiles	C1COCCN1C2=CC(=O)C3=C(O2)C(=CC=C3)C4=CC=CC5=C4SC6=CC=CC=C56
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 : 5 mg/mL ( (12.09 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。)

Water : Insoluble

Ethanol : 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

Clear solution

5%DMSO 1 40%PEG300 Click to order 2 5%Tween 80 Click to order 3 50%ddH2O

0.75mg/ml (1.81mM)

Taking the 1 mL working solution as an example, add 50 μL of 15 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

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

* 大学・企業名 大学・企業名を記入してください

* 名前 名前を記入してください

* 電子メール 電子メール・アドレスを記入してください 有効なメールアドレスを入力してください

電話番号

* 内容 お問い合わせ内容をご入力ください

よくある質問（FAQ）

質問1:
Could you please suggest formulations of the drug for in vivo injection?

回答
We tested the following formulation for in vivo use, 4% DMSO+30% PEG 300+5% Tween 80+ddH2O up to 1mg/mL. It is a clear solution.

質問2:
Previous aliquots were clear and colorless while this time, it becomes yellow when the powder was dissolved in DMSO? Could you advice on this?

回答
Slight color variation due to different processing is normal and usually doesn't interfere with the function.

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):