YO-01027 (Dibenzazepine, DBZ)
(Synonyms: 二苯并氮卓,gamma-Secretase Inhibitor XX,YO01027) 目录号 : GC17671
An inhibitor of γ-secretase
Cas No.:209984-56-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
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Pharmacological inhibition of γ-secretase activity |
For YO-01027, pilot experiments were performed with different drug concentrations ranging from 0.1 nM to 150 μM to determine the effective linear range and maximal inhibition dose for YO-01027. YO-01027 were added at the required concentrations to the S2 cell medium upon induction of Notch or APPL expression, 6 hrs before protein harvesting. For each sample, YO-01027 was also included at the corresponding concentration in the lysis buffer for protein extraction and immunoblot analysis. |
| Cell experiment [2]: | |
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Cell lines |
Breast cancer stem cells (BCSCs) |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reaction Conditions |
10 μM; 3 days |
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Applications |
YO-01027 (10 μM) reduced BCSC number and activity. |
| Animal experiment [3]: | |
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Animal models |
C57BL/6 mice |
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Dosage form |
0, 3, 10 and 30 μmol/kg; i.p.; q.d., for 5 days |
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Applications |
In C57BL/6 mice, YO-01027 treatment inhibited epithelial cell proliferation and induced goblet cell differentiation in intestinal adenomas in a dose-dependent manner. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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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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
[1].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
[2].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
| Cas No. | 209984-56-5 | SDF | |
| 别名 | 二苯并氮卓,gamma-Secretase Inhibitor XX,YO01027 | ||
| 化学名 | (2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]-N-[(7S)-5-methyl-6-oxo-7H-benzo[d][1]benzazepin-7-yl]propanamide | ||
| Canonical SMILES | CC(C(=O)NC1C2=CC=CC=C2C3=CC=CC=C3N(C1=O)C)NC(=O)CC4=CC(=CC(=C4)F)F | ||
| 分子式 | C26H23F2N3O3 | 分子量 | 463.48 |
| 溶解度 | ≥ 23.174 mg/mL in DMSO, ≥ 4.13 mg/mL in EtOH with ultrasonic and warming | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1576 mL | 10.788 mL | 21.5759 mL |
| 5 mM | 0.4315 mL | 2.1576 mL | 4.3152 mL |
| 10 mM | 0.2158 mL | 1.0788 mL | 2.1576 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。