产品号 #72792_C
Notch通路抑制剂；抑制γ分泌酶
总览
LY411575是一种细胞渗透性γ-分泌酶抑制剂（IC50 = 0.14 nM），在体外500µM时阻断Notch激活(Curry等人；Czirr等)通过γ-分泌酶抑制。Notch是一种跨膜受体，在细胞增殖、分化和凋亡等细胞命运决定中起关键作用。
分化
·促进小鼠胚胎干（ES）细胞衍生的神经祖细胞的神经元分化（branches等人；Aranha等人）。
·促进小鼠肠道和培养的结肠类器官的杯状细胞分化（Okamoto等；Yui等人）。
·体外诱导内耳干细胞向毛细胞分化，体内诱导支持细胞向毛细胞转分化（Bramhall等；Mizutari等人)。
·导致斑马鱼her4阳性祖细胞过早分化为神经元（Dirian等人）。
癌症研究
·诱导原代和永生化Karposi肉瘤细胞凋亡（Curry等）。
细胞类型
癌细胞及细胞系，肠道细胞，角质形成细胞，神经细胞，PSC衍生，神经元
种属
人，小鼠，非人灵长类，其它细胞系，大鼠
应用
分化，类器官培养
研究领域
癌症，上皮细胞研究，神经科学，干细胞生物学
CAS 编号
209984-57-6
化学式
C₂₆H₂₃F₂N₃O₄
分子量
479.5 克/摩尔
纯度
≥98%
通路
Notch
靶点
γ-分泌酶
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Applications
This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.
Resources and Publications
Educational Materials (3)
Publications (9)
Lgr5-positive supporting cells generate new hair cells in the postnatal cochlea. Stem cell reports 2014 MAR
Abstract
The prevalence of hearing loss after damage to the mammalian cochlea has been thought to be due to a lack of spontaneous regeneration of hair cells, the primary receptor cells for sound. Here, we show that supporting cells, which surround hair cells in the normal cochlear epithelium, differentiate into new hair cells in the neonatal mouse following ototoxic damage. Using lineage tracing, we show that new hair cells, predominantly outer hair cells, arise from Lgr5-expressing inner pillar and third Deiters cells and that new hair cell generation is increased by pharmacological inhibition of Notch. These data suggest that the neonatal mammalian cochlea has some capacity for hair cell regeneration following damage alone and that Lgr5-positive cells act as hair cell progenitors in the cochlea.
Spatial regionalization and heterochrony in the formation of adult pallial neural stem cells. Developmental cell 2014 JUL
Abstract
Little is known on the embryonic origin and related heterogeneity of adult neural stem cells (aNSCs). We use conditional genetic tracing, activated in a global or mosaic fashion by cell type-specific promoters or focal laser uncaging, coupled with gene expression analyses and Notch invalidations, to address this issue in the zebrafish adult telencephalon. We report that the germinal zone of the adult pallium originates from two distinct subtypes of embryonic progenitors and integrates two modes of aNSC formation. Dorsomedial aNSCs derive from the amplification of actively neurogenic radial glia of the embryonic telencephalon. On the contrary, the lateral aNSC population is formed by stepwise addition at the pallial edge from a discrete neuroepithelial progenitor pool of the posterior telencephalic roof, activated at postembryonic stages and persisting lifelong. This dual origin of the pallial germinal zone allows the temporally organized building of pallial territories as a patchwork of juxtaposed compartments.
Notch inhibition induces cochlear hair cell regeneration and recovery of hearing after acoustic trauma. Neuron 2013 JAN
Abstract
Hearing loss due to damage to auditory hair cells is normally irreversible because mammalian hair cells do not regenerate. Here, we show that new hair cells can be induced and can cause partial recovery of hearing in ears damaged by noise trauma, when Notch signaling is inhibited by a γ-secretase inhibitor selected for potency in stimulating hair cell differentiation from inner ear stem cells in vitro. Hair cell generation resulted from an increase in the level of bHLH transcription factor Atoh1 in response to inhibition of Notch signaling. In vivo prospective labeling of Sox2-expressing cells with a Cre-lox system unambiguously demonstrated that hair cell generation resulted from transdifferentiation of supporting cells. Manipulating cell fate of cochlear sensory cells in vivo by pharmacological inhibition of Notch signaling is thus a potential therapeutic approach to the treatment of deafness.
更多信息
| Molecular Weight | 479.5 g/mol |
|---|---|
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
| Cas Number | 209984-57-6 |
| Chemical Formula | C₂₆H₂₃F₂N₃O₄ |
| Purity | ≥ 98% |
| Target | γ-Secretase |
| Pathway | Notch |
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PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED.
