DBZ (Dibenzazepine)

別名：YO-01027

製品コード：S2711 純度：99.68%

DBZ (Dibenzazepine) is a dipeptidic γ-secretase inhibitor with IC50 of 2.6 nM and 2.9 nM in cell-free assays for APPL and Notch cleavage, respectively.

CAS No. 209984-56-5

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 55500	国内在庫あり
2mg	JPY 22000	国内在庫なし(納期7~10日)
5mg	JPY 40500	国内在庫あり
25mg	JPY 100500	国内在庫あり
1g	JPY 748500	国内在庫なし(納期7~10日)

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（38）

製品安全説明書

現在のバッチを見る：純度： 99.68%

99.68

DBZ (Dibenzazepine)関連製品

関連ターゲット	gamma-secretase	もっと見る
関連製品	DAPT RO4929097 LY411575 Avagacestat (BMS-708163) MK-0752 Semagacestat (LY450139) Nirogacestat (PF-03084014) MDL-28170 L-685,458	もっと見る
関連化合物ライブラリー	FDA-approved Drug Library Natural Product Library Bioactive Compound Library-I Protease Inhibitor Library Ubiquitination Compound Library	もっと見る

Secretase阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Incubation Time	活性情報	PMID
SupT1	Function assay	16 hrs	Inhibition of gamma secretase in human SupT1 cells assessed as reduction in amyloid beta 40 after 16 hrs by chemiluminescence assay, IC50=0.0026μM	27045975
SupT1	Function assay	16 hrs	Inhibition of gamma secretase mediated Notch signaling in human SupT1 cells after 16 hrs by chemiluminescence assay, IC50=0.0029μM	27045975
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
SK-N-SH	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
MG 63 (6-TG R)	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
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生物活性

製品説明

DBZ (Dibenzazepine) is a dipeptidic γ-secretase inhibitor with IC50 of 2.6 nM and 2.9 nM in cell-free assays for APPL and Notch cleavage, respectively.

Targets

γ secretase ^[1] (Cell-free assay)	Notch ^[1] (Cell-free assay)
2.6 nM	2.9 nM

In Vitro
In vitro	YO-01027 interacts directly with theγ-secretase complex and targets the N-terminal Presenilin fragment. Increasing concentrations of YO-01027 administered to APPL- or Notch-expressing cells leads to the progressive accumulation of APPL CTF fragments and a decrease in NICD production in a strictly dose-dependent manner. ^[1] 10 μM of YO-01027 reduces breast cancer stem cells (BCSC) number and activity. ^[2] A recent research indicates YO-01027 impairs mucin protein MUC16 biosynthesis in a concentration-dependent manner in undifferentiated cells at both preconfluent and confluent stages through Notch inhibition, but not in postmitotic stratified cells. ^[3]
Kinase Assay	Pharmacological Inhibition of γ-secretase Activity
Kinase Assay	For YO-01027, pilot experiments are performed with different drug concentrations ranging from 0.1 nM to 250 nM to determine the effective linear range and maximal inhibition dose for YO-01027. YO-01027 is added at the required concentrations to the S2 cell medium upon induction of Notch or APPL expression, 6 hours before protein harvesting. For each sample, YO-01027 is also included at the corresponding concentration in the lysis buffer for protein extraction and immunoblot analysis.
細胞実験	細胞株	BCSC
	濃度	10 μM
	反応時間	3 days
	実験の流れ	Cells are resuspended at ≤1 × 10⁶ in 100 μL sorting buffer (PBS containing 0.5% bovine serum albumin, 2 mM EDTA) and incubated with preconjugated primary antibodies BEREP4-FITC (1:10), CD44-APC (1:20), and CD24-PE (1:10) for 10 minutes at 4 °C. The cells are washed in PBS and centrifuged at 800 × g for 2 minutes. For analysis, cells are resuspended in 500 μL of sorting buffer and fluorescence is measured using FACSCalibur and analyzed using WinMIDI 2.8. For sorting, cells are resuspended in 1× HBSS after incubation with the primary antibodies. Cells are sorted, with HBSS as sheath fluid, at 16 p.s.i. using FACSAria. The CD24_low cell population gated by FACS is the lowest quintile of CD24-positive cells plus all the CD24-negative cells.

In Vivo
In Vivo	YO-01027, which is delivered 1 mg/mL by i.p. injection on the day of cell injection and every subsequent 3 days, YO-01027 significantly, decreases MCF7 but not MDA-MB-231 tumors and increases latency compared with control mice (18-28 days). YO-01027-treated MCF7 tumors that did form had significantly reduced tumor volumes. ^[2] Treatment of YO-01027 into C57BL/6 mice inhibits epithelial cell proliferation and induces goblet cell differentiation in intestinal adenomas in a dose-dependent manner. ^[4]
動物実験	動物モデル	C57BL/6 mice
	投与量	0, 3, 10, 30 μmol/kg
	投与経路	Injected daily intraperitoneally

参考
[1] Groth C, et al, Mol Pharmacol, 2010, 77(4), 567-574. [2] Harrison H, et al, Cancer Res, 2010, 70(2), 709-718. [3] Xiong L, et al, Invest Ophthalmol Vis Sci, 2011, 52(8), 5641-5646. [4] Van Es JH, et al, Nature, 2005, 435(7044), 959-963. + 展開

参考

[4] Van Es JH, et al, Nature, 2005, 435(7044), 959-963.

+ 展開

化学情報

分子量	463.48	化学式	C₂₆H₂₃F₂N₃O₃
CAS No.	209984-56-5	SDF	Download DBZ (Dibenzazepine) SDFをダウンロードする
Smiles	CC(C(=O)NC1C2=CC=CC=C2C3=CC=CC=C3N(C1=O)C)NC(=O)CC4=CC(=CC(=C4)F)F
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个月-20°Cin solvent

In vitro
Batch:

DMSO : 92 mg/mL ( (198.49 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 2 5%Tween80 3 50%ddH2O	1.1mg/ml (2.37mM)	Taking the 1 mL working solution as an example, add 50 μL of 22 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.	投与溶液組成計算機
Homogeneous suspension	0.5% hydroxyethyl cellulose	6.0mg/ml (12.95mM)	Taking the 1 mL working solution as an example, add 6 mg of this product to 1 ml of 0.5% hydroxyethyl cellulose clear solution, and mix evenly to form a uniform suspension. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil	0.75mg/ml (1.62mM)	Taking the 1 mL working solution as an example, add 50 μL of 15 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.

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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Handling Instructions

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よくある質問（FAQ）

質問1:
How to dissolve the compund for in vivo applications?

回答
For S2711, we suggest to use 0.5% hydroxyethyl cellulose in vivo study.

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