Ceralasertib (AZD6738)

製品コード：S7693 純度：99.71%

Ceralasertib (AZD6738) is an orally active, and selective ATR kinase inhibitor with IC50 of 1 nM. Phase 1/2.

CAS No. 1352226-88-0

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 41500	国内在庫あり
5mg	JPY 29500	国内在庫あり
25mg	JPY 104500	国内在庫あり
100mg	JPY 220500	国内在庫あり
1g	JPY 445500	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（121）

製品安全説明書

現在のバッチを見る：純度： 99.71%

99.71

Ceralasertib (AZD6738)と併用されることが多い化合物

Adavosertib (MK-1775)

Ceralasertib and Adavosertib combination exert more potent anti-tumor effects against biliary tract cancer.

Wang LW, et al. Molecules. 2022 Apr 12;27(8):2491.

VX-803 (M4344)

Compare with each other as ATR inhibitors.

Jo U, et al. Mol Cancer Ther. 2021;20(8):1431-1441.

Elimusertib (BAY-1895344)

Compare with each other as ATR inhibitors.

Sartori G, et al. bioRxiv 2023.02.10.528011

Ceralasertib (AZD6738)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 KU-60019 Berzosertib (VE-822) AZ20 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 cells	Function assay	75 mg/kg	8 hrs	Cp = 2.6 μM	30346772
HT-29 cells	Cytotoxicity assay		72 hrs	GI50 = 2.6 μM	30346772
LoVo cells	Function assay	25 mg/kg	8 hrs	Cp = 0.74 μM	30346772
LoVo cells	Function assay	50 mg/kg	8 hrs	Cp = 2.2 μM	30346772
LoVo cells	Cytotoxicity assay		72 hrs	GI50 = 0.44 μM	30346772
LICR-LON-HN4 and LICR-LON-HN5 cells	Function assay	0.03, 0.1, 0.3, 1, 3, 10 μM		AZD6738 inhibition of ATR through loss of downstream phosphorylation of CHK1 on Ser345.	30057890
K8484 cells	Function assay	2 μM	7 hours	In K8484 cells, AZD6738 at 2 µM completely prevented LY-188011-induced Chk1 phosphorylation on Serine 345, the downstream ATR target.	29891488
SNU-601 cells	Cell growth inhibition assay	0-1 μmol/L	5 days	The S and sub-G1 populations of SNU-601 cells were dramatically and dose-dependently increased by AZD6738.	28138034
HT29 cells	Function assay		60 mins	IC50 = 0.074 μM	30346772
LoVo cells	Function assay		24 h	Reduction in cell count; a proportion of the cell population are (in addition to cell cycle arrest) undergoing apoptosis when exposed to drug at concentrations greater than 3 μM	26310312
breast cancer cell lines	Cell growth inhibition assay	0.125, 0.25, 0.5 and 1.0 μM	5 days	IC50 values ranged from 0.3 to >1 μmol/L	27501113
MDA-MB-468 cells	Function assay			IC50 = 5.7 μM	30346772
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

Ceralasertib (AZD6738) is an orally active, and selective ATR kinase inhibitor with IC50 of 1 nM. Phase 1/2.

Targets

ATR ^[1]
(Cell-free assay)

1 nM

In Vitro
In vitro	In four Kras mutant cell lines: H23, H460, A549, and H358, AZD6738 inhibits ATR kinase activity and impairs cell viability. In ATM-deficient H23 cells, AZD6738 strongly synergizes with NSC 119875 to induce rapid cell death. ^[1] In p53 or ATM defective cells, AZD6738 treatment results in replication fork stalls and accumulation of unrepaired DNA damage, resulting in cell death by mitotic catastrophe. ^[2]
細胞実験	細胞株	H23, H460, A549, and H358 cells
	濃度	~30 μM
	反応時間	48 h
	実験の流れ	Cells are treated in white walled, clear bottom 96-well plates with the indicated doses of AZD6738, NSC 119875, LY-188011, or combination for 48 h. ATP levels are assessed as surrogate measure of viability is assessed using the CellTiter-Glo Luminescent Cell Viability Assay and Safire2 plate reader. Raw data are corrected for background luminescence prior to further analysis. For AZD6738 treatment, log dose response curves are generated in GraphPad Prism 6 by nonlinear regression (log(inhibitor) vs. response with variable slope) of log-transformed (x = log(x)) data normalized to the mean of untreated controls. GI50 values, defined as the dose X at which Y = 50%, were extrapolated from dose response curves.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	pCHK1 / pCDC25c / pRPA32 / γH2AX / pHH3 / cleaved caspase-3 / RAD51 ATM pSer1981 / ATM / ATR / Chk1 pSer345 / Chk1 / Chk2 pThr68 / Chk2		29605721
	Immunofluorescence	γH2AX / RAD51 53BP1		29605721
	Growth inhibition assay	Cell viability IC50		26563132

In Vivo
In Vivo	In nude mice bearing H460 and H23 tumors, AZD6738 (50 mg/kg, p.o.) results in tumor growth inhibition (TGI), and the the combination with NSC 119875 causes rapid regression of ATM-deficient H23 tumors. ^[1] In nude mice bearing LoVo xenografts, a combination of AZD6738 (50 mg/kg) + IR (2 Gy) avoids toxicity while still maintaining efficacy. ^[3]
動物実験	動物モデル	Female athymic nude mice bearing H23 or H460 xenografts
	投与量	25 or 50 mg/kg
	投与経路	p.o.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT05941897	Active not recruiting	Advanced or Metastatic NSCLC	AstraZeneca	June 21 2023	Phase 2
NCT05514132	Active not recruiting	Advanced Solid Tumours	AstraZeneca	September 23 2022	Phase 1
NCT05450692	Recruiting	Advanced or Metastatic Non-Small Cell Lung Cancer	AstraZeneca\|Parexel	September 15 2022	Phase 3
NCT05061134	Active not recruiting	Melanoma	AstraZeneca	August 11 2022	Phase 2
NCT05469919	Active not recruiting	Advanced Solid Malignancies	AstraZeneca	June 9 2022	Phase 1
NCT04704661	Recruiting	Advanced Breast Carcinoma\|Advanced Colon Carcinoma\|Advanced Colorectal Carcinoma\|Advanced Endometrial Carcinoma\|Advanced Gastric Carcinoma\|Advanced Gastroesophageal Junction Adenocarcinoma\|Advanced Malignant Solid Neoplasm\|Advanced Salivary Gland Carcinoma\|Anatomic Stage III Breast Cancer AJCC v8\|Anatomic Stage IIIA Breast Cancer AJCC v8\|Anatomic Stage IIIB Breast Cancer AJCC v8\|Anatomic Stage IIIC Breast Cancer AJCC v8\|Anatomic Stage IV Breast Cancer AJCC v8\|Clinical Stage III Gastric Cancer AJCC v8\|Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8\|Clinical Stage IV Gastric Cancer AJCC v8\|Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8\|Clinical Stage IVA Gastric Cancer AJCC v8\|Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8\|Clinical Stage IVB Gastric Cancer AJCC v8\|Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8\|HER2-Positive Breast Carcinoma\|Malignant Hepatobiliary Neoplasm\|Metastatic Breast Carcinoma\|Metastatic Gastroesophageal Junction Adenocarcinoma\|Metastatic Malignant Solid Neoplasm\|Pathologic Stage III Gastric Cancer AJCC v8\|Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8\|Pathologic Stage IIIA Gastric Cancer AJCC v8\|Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8\|Pathologic Stage IIIB Gastric Cancer AJCC v8\|Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8\|Pathologic Stage IIIC Gastric Cancer AJCC v8\|Pathologic Stage IV Gastric Cancer AJCC v8\|Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8\|Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8\|Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8\|Prognostic Stage III Breast Cancer AJCC v8\|Prognostic Stage IIIA Breast Cancer AJCC v8\|Prognostic Stage IIIB Breast Cancer AJCC v8\|Prognostic Stage IIIC Breast Cancer AJCC v8\|Prognostic Stage IV Breast Cancer AJCC v8\|Stage III Colon Cancer AJCC v8\|Stage III Colorectal Cancer AJCC v8\|Stage III Major Salivary Gland Cancer AJCC v8\|Stage III Uterine Corpus Cancer AJCC v8\|Stage IIIA Colon Cancer AJCC v8\|Stage IIIA Colorectal Cancer AJCC v8\|Stage IIIA Uterine Corpus Cancer AJCC v8\|Stage IIIB Colon Cancer AJCC v8\|Stage IIIB Colorectal Cancer AJCC v8\|Stage IIIB Uterine Corpus Cancer AJCC v8\|Stage IIIC Colon Cancer AJCC v8\|Stage IIIC Colorectal Cancer AJCC v8\|Stage IIIC Uterine Corpus Cancer AJCC v8\|Stage IIIC1 Uterine Corpus Cancer AJCC v8\|Stage IIIC2 Uterine Corpus Cancer AJCC v8\|Stage IV Colon Cancer AJCC v8\|Stage IV Colorectal Cancer AJCC v8\|Stage IV Major Salivary Gland Cancer AJCC v8\|Stage IV Uterine Corpus Cancer AJCC v8\|Stage IVA Colon Cancer AJCC v8\|Stage IVA Colorectal Cancer AJCC v8\|Stage IVA Major Salivary Gland Cancer AJCC v8\|Stage IVA Uterine Corpus Cancer AJCC v8\|Stage IVB Colon Cancer AJCC v8\|Stage IVB Colorectal Cancer AJCC v8\|Stage IVB Major Salivary Gland Cancer AJCC v8\|Stage IVB Uterine Corpus Cancer AJCC v8\|Stage IVC Colon Cancer AJCC v8\|Stage IVC Colorectal Cancer AJCC v8\|Stage IVC Major Salivary Gland Cancer AJCC v8\|Unresectable Colorectal Carcinoma\|Unresectable Gastroesophageal Junction Adenocarcinoma\|Unresectable Malignant Solid Neoplasm	National Cancer Institute (NCI)	August 9 2021	Phase 1

参考
[1] Vendetti FP, et al. Oncotarget. 2015. doi: 10.18632/oncotarget.6247. [2] Kwok M, et al. Lancet. 2015. doi: 10.1016/S0140-6736(15)60373-7. [3] Checkley S, et al. Sci Rep. 2015. doi: 10.1038/srep13545.

参考

化学情報

分子量	412.51	化学式	C₂₀H₂₄N₆O₂S
CAS No.	1352226-88-0	SDF	Download Ceralasertib (AZD6738) SDFをダウンロードする
Smiles	CC1COCCN1C2=NC(=NC(=C2)C3(CC3)S(=N)(=O)C)C4=C5C=CNC5=NC=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ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 82 mg/mL ( (198.78 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 : 82 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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C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
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