EasySep™小鼠TIL（CD45）正选试剂盒
产品号 #73092_C
Notch通路抑制剂；抑制γ分泌酶
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总览
DBZ是一种γ-分泌酶的二氮卓类抑制剂，该酶能切割多种跨膜蛋白，包括Notch、淀粉样前体蛋白（APP）和Ephrin-B2 （Borgegard等人）。DBZ 可阻断Notch蛋白被切割生成其活性信号效应物 —— Notch 胞内结构域（NICD），IC₅₀为1.7 nM （Milano等人）。
重编程
·在不存在致癌重编程因子KLF4和c-MYC的情况下，诱导人角质形成细胞重编程为诱导多能干细胞（iPSCs）（Ichida等人）。
分化
·在大鼠中诱导肠道细胞凋亡和杯状细胞化生；缓解因结节性硬化症 2 型（TSC2） 抑制所导致的潘氏细胞和杯状细胞减少（Milano 等人；Zhou 等人）。
代谢
·改善小鼠的葡萄糖稳态，并介导代谢向利用脂肪作为能量来源的转变（Bi等人）。
癌症研究
·诱导Apc（Min）转基因小鼠肠腺瘤分化（van Es 等人）。
·小鼠骨髓移植后，减少同种异体反应性T细胞产生的炎症细胞因子，从而降低移植物抗宿主病的严重程度（Tran等人）。
细胞类型
癌细胞及细胞系，肠道细胞，多能干细胞，T 细胞
种属
人，小鼠，非人灵长类，其他物种，大鼠
应用
重编程
研究领域
癌症，上皮细胞研究，免疫，代谢，干细胞生物学，移植研究
CAS 编号
209984-56-5
化学式
C₂₆H₂₃F₂N₃O₃
纯度
≥98%
通路
Notch
靶点
γ-分泌酶
产品说明书及文档
请在《产品说明书》中查找相关支持信息和使用说明，或浏览下方更多实验方案。
应用领域
本产品专为以下研究领域设计，适用于工作流程中的高亮阶段。探索这些工作流程，了解更多我们为各研究领域提供的其他配套产品。
相关材料与文献
技术资料 (3)
文献 (9)
Modulation of notch processing by gamma-secretase inhibitors causes intestinal goblet cell metaplasia and induction of genes known to specify gut secretory lineage differentiation.
Toxicological sciences : an official journal of the Society of Toxicology 2004
Abstract
It is anticipated that gamma-secretase inhibitors (gamma-Sec-I) that modulate Notch processing will alter differentiation in tissues whose architecture is governed by Notch signaling. To explore this hypothesis,Han Wistar rats were dosed for up to 5 days with 10-100 micromol/kg b.i.d. gamma-Sec-I from three chemical series that inhibit Notch processing in vitro at various potencies (Notch IC(50)). These included an arylsulfonamide (AS) (142 nM),a dibenzazepine (DBZ) (1.7 nM),and a benzodiazepine (BZ) (2.2 nM). The DBZ and BZ caused dose-dependent intestinal goblet cell metaplasia. In contrast,the AS produced no detectable in vivo toxicity,despite higher exposure to free drug. In a time course using BZ,small intestinal crypt cell and large intestinal glandular cell epithelial apoptosis was observed on days 1-5,followed by goblet cell metaplasia on days 2-5 and crypt epithelial and glandular epithelial regenerative hyperplasia on days 4-5. Gene expression profiling of duodenal samples from BZ-dosed animals revealed significant time-dependent deregulation of mRNAs for various panendocrine,hormonal,and transcription factor genes. Somatostatin,secretin,mucin,CCK,and gastrin mRNAs were elevated twofold or more by day 2,and a number of candidate early-predictive" genes were altered on days 1-2�
Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells.
Nature 2005
Abstract
The self-renewing epithelium of the small intestine is ordered into stem/progenitor crypt compartments and differentiated villus compartments. Recent evidence indicates that the Wnt cascade is the dominant force in controlling cell fate along the crypt-villus axis. Here we show a rapid,massive conversion of proliferative crypt cells into post-mitotic goblet cells after conditional removal of the common Notch pathway transcription factor CSL/RBP-J. We obtained a similar phenotype by blocking the Notch cascade with a gamma-secretase inhibitor. The inhibitor also induced goblet cell differentiation in adenomas in mice carrying a mutation of the Apc tumour suppressor gene. Thus,maintenance of undifferentiated,proliferative cells in crypts and adenomas requires the concerted activation of the Notch and Wnt cascades. Our data indicate that gamma-secretase inhibitors,developed for Alzheimer's disease,might be of therapeutic benefit in colorectal neoplastic disease.
Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke.
Nature medicine 2006 JUN
Abstract
Mice transgenic for antisense Notch and normal mice treated with inhibitors of the Notch-activating enzyme gamma-secretase showed reduced damage to brain cells and improved functional outcome in a model of focal ischemic stroke. Notch endangers neurons by modulating pathways that increase their vulnerability to apoptosis,and by activating microglial cells and stimulating the infiltration of proinflammatory leukocytes. These findings suggest that Notch signaling may be a therapeutic target for treatment of stroke and related neurodegenerative conditions.
更多信息
| 物种 | 人, 其它物种, 大鼠, 小鼠, 非人灵长类 |
|---|---|
| Cas Number | 209984-56-5 |
| Chemical Formula | C₂₆H₂₃F₂N₃O₃ |
| 纯度 | ≥ 98% |
| Target | γ-Secretase |
| Pathway | Notch |
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