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，其它细胞系，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
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相关材料与文献
技术资料 (3)
文献 (9)
TSC2/mTORC1 signaling controls Paneth and goblet cell differentiation in the intestinal epithelium. Cell death & disease 2015 JAN
Abstract
The intestinal mucosa undergoes a continual process of proliferation, differentiation and apoptosis, which is regulated by multiple signaling pathways. Notch signaling is critical for the control of intestinal stem cell maintenance and differentiation. However, the precise mechanisms involved in the regulation of differentiation are not fully understood. Previously, we have shown that tuberous sclerosis 2 (TSC2) positively regulates the expression of the goblet cell differentiation marker, MUC2, in intestinal cells. Using transgenic mice constitutively expressing a dominant negative TSC2 allele, we observed that TSC2 inactivation increased mTORC1 and Notch activities, and altered differentiation throughout the intestinal epithelium, with a marked decrease in the goblet and Paneth cell lineages. Conversely, treatment of mice with either Notch inhibitor dibenzazepine (DBZ) or mTORC1 inhibitor rapamycin significantly attenuated the reduction of goblet and Paneth cells. Accordingly, knockdown of TSC2 activated, whereas knockdown of mTOR or treatment with rapamycin decreased, the activity of Notch signaling in the intestinal cell line LS174T. Importantly, our findings demonstrate that TSC2/mTORC1 signaling contributes to the maintenance of intestinal epithelium homeostasis by regulating Notch activity.
Notch inhibition allows oncogene-independent generation of iPS cells. Nature chemical biology 2014 AUG
Abstract
The reprogramming of somatic cells to pluripotency using defined transcription factors holds great promise for biomedicine. However, human reprogramming remains inefficient and relies either on the use of the potentially dangerous oncogenes KLF4 and CMYC or the genetic inhibition of the tumor suppressor gene p53. We hypothesized that inhibition of signal transduction pathways that promote differentiation of the target somatic cells during development might relieve the requirement for non-core pluripotency factors during induced pluripotent stem cell (iPSC) reprogramming. Here, we show that inhibition of Notch greatly improves the efficiency of iPSC generation from mouse and human keratinocytes by suppressing p21 in a p53-independent manner and thereby enriching for undifferentiated cells capable of long-term self-renewal. Pharmacological inhibition of Notch enabled routine production of human iPSCs without KLF4 and CMYC while leaving p53 activity intact. Thus, restricting the development of somatic cells by altering intercellular communication enables the production of safer human iPSCs.
Inhibition of Notch signaling promotes browning of white adipose tissue and ameliorates obesity. Nature medicine 2014 AUG
Abstract
Beige adipocytes in white adipose tissue (WAT) are similar to classical brown adipocytes in that they can burn lipids to produce heat. Thus, an increase in beige adipocyte content in WAT browning would raise energy expenditure and reduce adiposity. Here we report that adipose-specific inactivation of Notch1 or its signaling mediator Rbpj in mice results in browning of WAT and elevated expression of uncoupling protein 1 (Ucp1), a key regulator of thermogenesis. Consequently, as compared to wild-type mice, Notch mutants exhibit elevated energy expenditure, better glucose tolerance and improved insulin sensitivity and are more resistant to high fat diet-induced obesity. By contrast, adipose-specific activation of Notch1 leads to the opposite phenotypes. At the molecular level, constitutive activation of Notch signaling inhibits, whereas Notch inhibition induces, Ppargc1a and Prdm16 transcription in white adipocytes. Notably, pharmacological inhibition of Notch signaling in obese mice ameliorates obesity, reduces blood glucose and increases Ucp1 expression in white fat. Therefore, Notch signaling may be therapeutically targeted to treat obesity and type 2 diabetes.
更多信息
| 种属 | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 209984-56-5 |
| Chemical Formula | C₂₆H₂₃F₂N₃O₃ |
| 纯度 | ≥ 98% |
| Target | γ-Secretase |
| Pathway | Notch |
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