YO-01027 (Dibenzazepine, DBZ)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
YO-01027（Dibenzazepine，DBZ）是一种有效的γ-分泌酶抑制剂。γ-分泌酶是一个多亚基天冬氨酸蛋白酶，催化众多I型整合膜蛋白（如淀粉样前体蛋白（APP）和Notch）的裂解。YO-01027以剂量依赖的方式与Presenilin的N端相互作用，从而有效阻断淀粉样前体蛋白样（APPL）和Notch的裂解，IC50值分别为2.640.30 nM和2.920.22 nM。最近的研究表明，YO-01027诱导的对Notch信号传导途径的抑制导致增值性隐窝细胞向有丝分裂后细胞的快速转换，以浓度依赖的方式损害预融合和融合阶段未分化细胞，而非有丝分裂后分层细胞中MUC16的生物合成。
参考文献：
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
- 1. Yu-Hwai Tsai, Angeline Wu, et al. "Acquisition of NOTCH dependence is a hallmark of human intestinal stem cell maturation." Stem Cell Reports. 2022 May 10;17(5):1138-1153. PMID: 35395175
- 2. Ireland AS, Micinski AM, et al. "MYC Drives Temporal Evolution of Small Cell Lung Cancer Subtypes by Reprogramming Neuroendocrine Fate." Cancer Cell. 2020;S1535-6108(20)30218-X. PMID: 32473656
- 3. Zhu M, Li Y, et al. "Effects of bisphenol A and its alternative bisphenol F on Notch signaling and intestinal development: A novel signaling by which bisphenols disrupt vertebrate development." Environ Pollut. 2020;263(Pt B):114443. PMID: 32311622
- 4. Zhu M, Niu Y, et al. "Low Concentrations of Tetrabromobisphenol A Disrupt Notch Signaling and Intestinal Development in in Vitro and in Vivo Models." Chem Res Toxicol. 2020;10.1021/acs.chemrestox.9b00528. PMID: 32041402
- 5. 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
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 463.48 |
| Cas No. | 209984-56-5 |
| Formula | C26H23F2N3O3 |
| Synonyms | gamma-Secretase Inhibitor XX,YO01027 |
| Solubility | ≥23.17 mg/mL in DMSO; insoluble in H2O; ≥4.13 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | (2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]-N-[(7S)-5-methyl-6-oxo-7H-benzo[d][1]benzazepin-7-yl]propanamide |
| SDF | Download SDF |
| Canonical SMILES | CC(C(=O)NC1C2=CC=CC=C2C3=CC=CC=C3N(C1=O)C)NC(=O)CC4=CC(=CC(=C4)F)F |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 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。溶液形式一般不宜长期储存，请尽快用完。 |
| 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. |
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| 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 | ||||
质量控制和MSDS
- 批次:
化学结构
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