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PluriSIn-1

油酸生物合成途径抑制剂;抑制硬脂酰辅酶A去饱和酶(SCD1)

产品号 #(选择产品)

产品号 #72822_C

油酸生物合成途径抑制剂;抑制硬脂酰辅酶A去饱和酶(SCD1)

总览

PluriSIn-1是一种N-酰基苯肼类化合物,可抑制硬脂酰辅酶A去饱和酶,该酶在人多能干细胞中表达的脂质代谢的关键酶(Ben-David et al.)。

分化
·可选择性去除未分化的人胚胎干细胞(ES)和诱导多能干细胞(iPS),同时保留已分化的细胞,在小鼠移植实验中可防止畸胎瘤形成(Ben-David et al.)。
·在体外诱导Nanog阳性iPS细胞凋亡,而不影响iPS细胞衍生的心肌细胞(Zhang et al.)。

细胞类型
心肌细胞,PSC衍生,多能干细胞
 
种属
人,小鼠,非人灵长类,其它细胞系,大鼠
 
应用
分化
 
研究领域
干细胞生物学
 
CAS 编号
91396-88-2
 
化学式
C₁₂H₁₁N₃O
 
纯度
≥ 95 %
 
通路
油酸
 
靶点
SCD1
 

产品说明书及文档

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Document Type
Product Name
Catalog #
Lot #
Language
Product Name
PluriSIn-1
Catalog #
72822
Lot #
All
Language
English
Document Type
Safety Data Sheet
Product Name
PluriSIn-1
Catalog #
72822
Lot #
All
Language
English

应用领域

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相关材料与文献

技术资料 (3)

文献 (2)

Inhibition of stearoyl-coA desaturase selectively eliminates tumorigenic Nanog-positive cells: improving the safety of iPS cell transplantation to myocardium. Zhang L et al. Cell cycle (Georgetown, Tex.) 2014 MAR

Abstract

Induced pluripotent stem cells (iPS) can differentiate into cardiomyocytes (CM) and represent a promising form of cellular therapy for heart regeneration. However, residual undifferentiated iPS derivates (iPSD), which are not fully eliminated by cell differentiation or purification protocols, may form tumors after transplantation, thus compromising therapeutic application. Inhibition of stearoyl-coA desaturase (SCD) has recently been reported to eliminate undifferentiated human embryonic stem cells, which share many features with iPSD. Here, we tested the effects of PluriSin1, a small-molecule inhibitor of SCD, on iPS-derived CM. We found that plurisin1 treatment significantly decreased the mRNA and protein level of Nanog, a marker for both cell pluripotency and tumor progression; importantly, we provide evidence that PluriSin1 treatment at 20 µM for 1 day significantly induces the apoptosis of Nanog-positive iPSD. In addition, PluriSin1 treatment at 20 µM for 4 days diminished Nanog-positive stem cells in cultured iPSD while not increasing apoptosis of iPS-derived CM. To investigate whether PluriSin1 treatment prevents tumorigenicity of iPSD after cell transplantation, we intramyocardially injected PluriSin1- or DMSO-treated iPSD in a mouse model of myocardial infarction (MI). DMSO-treated iPSD readily formed Nanog-expressing tumors 2 weeks after injection, which was prevented by treatment with PluriSin1. Moreover, treatment with PluriSin1 did not change the expression of cTnI, α-MHC, or MLC-2v, markers of cardiac differentiation (Ptextgreater0.05, n = 4). Importantly, pluriSin1-treated iPS-derived CM exhibited the ability to engraft and survive in the infarcted myocardium. We conclude that inhibition of SCD holds the potential to enhance the safety of therapeutic application of iPS cells for heart regeneration.
Selective elimination of human pluripotent stem cells by an oleate synthesis inhibitor discovered in a high-throughput screen Ben-David U et al. Cell stem cell 2013 FEB

Abstract

The use of human pluripotent stem cells (hPSCs) in cell therapy is hindered by the tumorigenic risk from residual undifferentiated cells. Here we performed a high-throughput screen of over 52,000 small molecules and identified 15 pluripotent cell-specific inhibitors (PluriSIns), nine of which share a common structural moiety. The PluriSIns selectively eliminated hPSCs while sparing a large array of progenitor and differentiated cells. Cellular and molecular analyses demonstrated that the most selective compound, PluriSIn 1, induces ER stress, protein synthesis attenuation, and apoptosis in hPSCs. Close examination identified this molecule as an inhibitor of stearoyl-coA desaturase (SCD1), the key enzyme in oleic acid biosynthesis, revealing a unique role for lipid metabolism in hPSCs. PluriSIn 1 was also cytotoxic to mouse blastocysts, indicating that the dependence on oleate is inherent to the pluripotent state. Finally, application of PluriSIn 1 prevented teratoma formation from tumorigenic undifferentiated cells. These findings should increase the safety of hPSC-based treatments. ?? 2013 Elsevier Inc.

更多信息

更多信息
种属 Human, Mouse, Non-Human Primate, Other, Rat
Cas Number 91396-88-2
Chemical Formula C₁₂H₁₁N₃O
纯度 ≥ 95%
Target SCD1
Pathway Oleic Acid
质量保证:

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