产品号 #72792_C
Notch pathway inhibitor; Inhibits γ-secretase
概述
LY411575 is a cell-permeable γ-secretase inhibitor (IC₅₀ = 0.14 nM) that blocks Notch activation in vitro at 500 µM (Curry et al.; Czirr et al.) via γ-Secretase inhibition. Notch is a transmembrane receptor that plays a key role in cell fate decisions including cell proliferation, differentiation, and apoptosis.
DIFFERENTIATION
· Promotes neuronal differentiation of neural progenitor cells derived from mouse embryonic stem (ES) cells (Abranches et al.; Aranha et al.).
· Promotes goblet cell differentiation in mouse intestine and cultured colonic organoids (Okamoto et al.; Yui et al.).
· Induces hair cell differentiation from inner ear stem cells in vitro, and transdifferentiation of supporting cells into hair cells in vivo (Bramhall et al.; Mizutari et al.).
· Causes premature differentiation of Her4-positive progenitors into neurons in zebrafish (Dirian et al.).
CANCER RESEARCH
· Induces apoptosis in primary and immortalized Karposi’s sarcoma cells (Curry et al.).
Cell Type
Cancer Cells and Cell Lines, Intestinal Cells, Keratinocytes, Neural Cells, PSC-Derived, Neurons
Species
Human, Mouse, Non-Human Primate, Other, Rat
Application
Differentiation, Organoid Culture
Area of Interest
Cancer, Epithelial Cell Biology, Neuroscience, Stem Cell Biology
CAS Number
209984-57-6
Chemical Formula
C₂₆H₂₃F₂N₃O₄
Molecular Weight
479.5 g/mol
Purity
≥ 98%
Pathway
Notch
Target
γ-Secretase
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Applications
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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.
PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED.
