Z-Ile-Leu-aldehyde
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.
Z-Ile-Leu-aldehyde(gamma-Secretase inhibitor XII /GSI XII,Z-IL-CHO)是一种有效的γ-分泌酶抑制剂;也是Notch信号传导抑制剂.
Notch信号传导影响许多细胞过程,包括细胞增殖\分化\凋亡和干细胞的维持.它还参与许多发育系统,包括神经发生\血管发生\造血和肌生成.Notch信号的失调导致发育综合征和癌症[3].为了传递信号,Notch受体在结合其Delta样和 Jagged家族的同源配体后经历一系列蛋白水解切割.γ分泌酶是一种大的蛋白酶复合物,可以切割膜结合形式的Notch,并释放Notch受体的细胞内结构域.Notch信号的这一步骤在其信号级联的激活中是非常关键的[1] [2].
体外:在体外用GSI XII(10〜15 μM)处理MOPC315.BM鼠多发性骨髓瘤细胞,发现GSI XII阻断Notch信号传导,降低细胞活力并诱导细胞凋亡.在NF-κB配体受体激活剂(RANKL)刺激的RAW264.7鼠单核细胞/巨噬细胞系中,发现GSI XII(10 μM)损伤破骨细胞的分化[1]. GSI XII(8 μM〜15 μM)抑制乳腺癌细胞中的Notch活性,从而引发凋亡反应.GSI XII还靶向乳腺癌干细胞,因为它可以显著地防止体外乳腺卵泡的形成[3].
体内:在MOPC315.BM小鼠模型中, GSI XII(腹膜内注射,10 mg/kg)通过抑制Notch降低骨髓瘤特异性副蛋白的水平,降低骨丢失,并减少溶骨性病变 [1].GSI-XII(腹膜内注射,5 mg/kg)还可通过抑制Notch来阻断小鼠胚胎性横纹肌肉瘤的肿瘤发生[2].
离体:通过建立人乳腺癌组织的三维培养模型,来研究连续30例来自未经治疗乳腺癌患者的原发肿瘤对Notch抑制剂GSI XII(15 μM)的敏感性.离体实验发现有24例肿瘤对GSI XII诱导的凋亡敏感.
References:
[1]. Schwarzer R, Nickel N, Godau J, et al. Notch pathway inhibition controls myeloma bone disease in the murine MOPC315. BM model[J]. Blood cancer journal, 2014, 4(6): e217.
[2]. Belyea B C, Naini S, Bentley R C, et al. Inhibition of the Notch-Hey1 axis blocks embryonal rhabdomyosarcoma tumorigenesis[J]. Clinical Cancer Research, 2011, 17(23): 7324-7336.
[3]. Séveno C, Loussouarn D, Bréchet S, et al. γ-Secretase inhibition promotes cell death, Noxa upregulation, and sensitization to BH3 mimetic ABT-737 in human breast cancer cells[J]. Breast Cancer Research, 2012, 14(3): R96.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 362.46 |
| Cas No. | 161710-10-7 |
| Formula | C20H30N2O4 |
| Solubility | insoluble in EtOH; insoluble in H2O; ≥10.8 mg/mL in DMSO |
| Chemical Name | benzyl ((2R,3R)-3-methyl-1-(((R)-4-methyl-1-oxopentan-2-yl)amino)-1-oxopentan-2-yl)carbamate |
| SDF | Download SDF |
| Canonical SMILES | O=C(N[C@@H](C(N[C@@H](C=O)CC(C)C)=O)[C@@H](CC)C)OCC1=CC=CC=C1 |
| 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。 |
质量控制和MSDS
- 批次:
化学结构
