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YO-01027 (Dibenzazepine, DBZ)

现货
Catalog No.
A4018
γ-分泌酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,000.00
现货
5mg
¥ 1,030.00
现货
10mg
¥ 1,850.00
现货
25mg
¥ 3,790.00
现货
50mg
¥ 5,610.00
现货

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Background

YO-01027, also known as dibenzazepine or DBZ, is a potent inhibitor of γ-secretase, a multisubunit aspartyl protease catalyzing the cleavage of numerous type I integral membrane proteins (such as amyloid precursor protein (APP) and Notch). YO-01027 also potently blocks amyloid precursor protein-like (APPL) and Notch cleavage, with estimated inhibition constant IC50 of 2.640.30 nM and 2.920.22 nM respectively, through interaction with the N-terminal fragment of Presenilin in a dose-response manner. Recent studies show that YO-01027-induced inhibition Notch signaling pathway leads to a rapid conversion of proliferative crypt cells into postmitotic cells and impairs MUC16 biosynthesis in a concentration-dependent manner in undifferentiated cells instead of postmiotic stratified cells at both preconfluent and confluent stages.

Reference

Linjie Xiong, Ashley M. Woodward, and Pablo Argueso. Notch signaling modulates MUC16 biosynthesis in an vitro model of human corneal and conjunctival epithelial cell differentiation. Invest. Ophthalmol. Vis. Sci. 2011, 52(8), 5641-5646

Casper Groth, W. Gregory Alvord, Octavio A. Quinones, and Mark E. Fortini. Pharmacological analysis of drosphila melanogaster γ-secretase with respect to differential proteolysis of Notch and APP. Mol. Pharmacol. 2010, 77(4), 567-574

文献引用

1. Idowu J, Home T, et al. "Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney Disease." Sci Rep. 2018 Feb 20;8(1):3340. PMID:29463793

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt463.48
Cas No.209984-56-5
FormulaC26H23F2N3O3
Synonymsgamma-Secretase Inhibitor XX,YO01027
Solubility≥23.174 mg/mL in DMSO, ≥4.13 mg/mL in EtOH with ultrasonic and warming, <2.51 mg/mL in H2O
Chemical Name(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]-N-[(7S)-5-methyl-6-oxo-7H-benzo[d][1]benzazepin-7-yl]propanamide
SDFDownload SDF
Canonical SMILESCC(C(=O)NC1C2=CC=CC=C2C3=CC=CC=C3N(C1=O)C)NC(=O)CC4=CC(=CC(=C4)F)F
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

γ-分泌酶活性抑制

对于YO-01027,采用不同药物浓度(0.1 nM ~ 150 μM)进行先导实验,以测定YO-01027的有效线性范围和最大抑制剂量。在收集蛋白的6小时之前,根据Notch 或 APPL表达的诱导情况,将YO-01027按所需浓度加入到S2细胞培养基中。对于每个样品,将相应浓度的YO-01027 加入到裂解缓冲液中,随后进行蛋白萃取和免疫印迹分析。

细胞实验 [2]:

细胞系

乳腺癌干细胞(BCSCs)

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

10 μM;3天

实验结果

YO-01027 (10 μM) 减少BCSC数量与活性。

动物实验 [3]:

动物模型

C57BL/6小鼠

给药剂量

0、3、10和30 μmol/kg;腹腔注射;每日1次,持续5天

实验结果

在C57BL/6小鼠中,YO-01027治疗抑制上皮细胞增殖,并呈剂量依赖性地诱导肠腺瘤杯状细胞分化。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Casper Groth, W. Gregory Alvord, Octavio A. Quinones, and Mark E. Fortini. Pharmacological analysis of drosphila melanogaster γ-secretase with respect to differential proteolysis of Notch and APP. Mol. Pharmacol. 2010, 77(4), 567-574.

[2]. Harrison H, Farnie G, Howell SJ, Rock RE, Stylianou S, Brennan KR, Bundred NJ, Clarke RB. Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor. Cancer Res. 2010 Jan 15;70(2):709-18.

[3]. van Es JH, van Gijn ME, Riccio O, van den Born M, Vooijs M, Begthel H, Cozijnsen M, Robine S, Winton DJ, Radtke F, Clevers H. Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature. 2005 Jun 16;435(7044):959-63.

生物活性

描述 YO-01027 (Dibenzazepine, DBZ)是γ-分泌酶的二肽酶抑制剂,作用于APPL和Notch的裂解,IC50值分别为2.6 nM和2.9 nM。
靶点 APPL Notch        
IC50 2.6 nM 2.9 nM        

质量控制

化学结构

YO-01027 (Dibenzazepine, DBZ)

相关生物数据

YO-01027 (Dibenzazepine, DBZ)

相关生物数据

YO-01027 (Dibenzazepine, DBZ)

相关生物数据

YO-01027 (Dibenzazepine, DBZ)

相关生物数据

YO-01027 (Dibenzazepine, DBZ)