AZ31

製品コードS8556 バッチS855601

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


* <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 is a selective and novel ATM inhibitor with an IC50 of <0.0012 μM. It shows excellent selectivity over closely related enzymes (>500 fold selective over DNA-PK and PI3Kα and >1000 fold selective over mTOR, PI3Kβ and PI3Kγ).
in vitro	Antitumor effects of AZ31 + SN38 are cytostatic rather than cytotoxic^[1].
in vivo	Pharmacokinetic investigation of AZ31 as a single agent and in combination with irinotecan revealed that plasma concentrations of AZ31 were highest 1-hour after administration followed by a stepwise decrease at 3, 6 and 16 hour in the combination sensitive CRC098^[1].

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 AZ31 + 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

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。

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