AZ31

製品コードS8556 バッチS855601

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₂₄H₂₈N₄O₃

分子量

420.50

CAS No.

2088113-98-6

Solubility (25°C)*

体外

体内（毎回新しく調製した物を用意してください）

Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	5.000mg/ml (11.89mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 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.
Clear solution	5% DMSO 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.830mg/ml (1.97mM)	Taking the 1 mL working solution as an example, add 50 μL of 16.6 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

生物活性

製品説明	AZ31 は、IC50 が 0.0012 μM 未満の選択的かつ新規の ATM 阻害剤です。関連酵素に対して優れた選択性を示します（DNA-PK および PI3Kα に対して 500 倍超、mTOR、PI3Kβ および PI3Kγ に対して 1000 倍超の選択性を示します）。
in vitro	Antitumor effects of AZ31 + SN38 are cytostatic rather than cytotoxic.
in vivo	Pharmacokinetic investigation of AZ31 as a single agent and in combination with irinotecan revealed that plasma concentrations of this compound were highest 1-hour after administration followed by a stepwise decrease at 3, 6 and 16 hour in the combination sensitive CRC098.

プロトコル(参考用のみ)

キナーゼアッセイ	ATM enzyme assay
キナーゼアッセイ	Compounds in 100% DMSO were added to assay plates by acoustic dispensing. ATM enzyme was added in a Hepes buffer (50 mM HEPES pH 7.4, 150 mM NaCl, 10 mM, MnCl2 1 mM, DTT, 5% v/v Glycerol, 0.05% v/v Tween 20) and allowed to preincubate with compound for 30 minutes prior to addition of substrate solution containing p53 and ATP. The enzyme reaction was stopped after 2 hours by the addition of detection reagent (33 mM HEPES pH 7.4, 20 mM EDTA, 0.1 M KF, 0.1 mg/mL BSA, 13 nM D2 Anti-GST antibody (Cisbio) and 0.5 nM Eu3+ Anti-p53phosphoS15 antibody) and incubated overnight before reading on a Pherastar Instrument with a standard HTRF filter block method. The final concentrations of DMSO, ATP and p53 in the assay were 1%, 5 µM, and 50 nM respectively. IC50 values (concentrations of test compound that inhibited 50% of enzyme activity) were determined using a four parameter fit method (smart fitting model) in the data analysis software.
細胞アッセイ	細胞株	CRC (metastatic colorectal cancer) cell lines: HCT15, HCT116, RKO, CaCo2, LS123 and LOVO
	濃度	1.25, 2.5 or 5 μmol/L
	反応時間	72 hours
	実験の流れ	Six CRC cell lines were treated with AZ31 (dose 1.25, 2.5 or 5 μmol/L), SN38 (0.3125 -20 nM) or this compound + SN38 and proliferation was determined by an SRB assay.
動物実験	動物モデル	CRC PDX models (Four-to-six week-old female athymic nude mice with implanted patient-derived colorectal adenocarcinoma tumor)
	投薬量	100 mg/kg-daily × 3
	投与方法	by oral gavage

参考

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762293/
https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.6b00519

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

HSATII RNA is induced via a noncanonical ATM-regulated DNA damage response pathway and promotes tumor cell proliferation and movement [ Proc Natl Acad Sci U S A, 2020, 117(50):31891-31901]	PubMed: 33257565

HSATII RNA is induced via a noncanonical ATM-regulated DNA damage response pathway and promotes tumor cell proliferation and movement [ Proc Natl Acad Sci U S A, 2020, 117(50):31891-31901]

PubMed: 33257565

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。