EasySep™小鼠TIL（CD45）正选试剂盒
产品号 #73412_C
Hedgehog通路激活剂；激活Smoothened（SMO）
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总览
SAG （Smoothened Agonist）是一种含氯苯并噻吩的化合物，作为G蛋白偶联受体Smoothened（SMO, EC₅₀=3 nM；Chen et al.）的激活剂。SMO是Hedgehog信号通路的组成部分，在Patched受体受到Hedgehog家族配体刺激后，SMO会转位至初级纤毛，从而激活通路。SAG通过直接结合七螺旋束（Kd=59 nM）来激活SMO ，从而稳定纤毛中SMO的特定构象，并导致下游基因表达增加（Rohatgi et al.）。SAG可消除环巴胺对SMO的抑制作用，表明其作用于环巴胺的下游（Frank-Kamenetsky et al.; Chen et al.; Lewis & Krieg）。
分化
·促进人诱导多能干细胞的神经元分化（Mak et al.）。
维持培养
·在体内和体外诱导神经元和神经胶质前体的增殖和存活（Bragina et al.）。
·防Math1-Cre、SmoM2转基因小鼠的糖皮质激素神经毒性（Heine et al.）。
·挽救唐氏综合征Ts65Dn小鼠模型的小脑大小和行为表型（Das et al.）。
细胞类型
神经细胞，PSC衍生，神经干/祖细胞，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，扩增，培养
研究领域
疾病建模，神经科学，干细胞生物学
CAS 编号
912545-86-9
化学式
C₂₈H₂₈ClN₃OS
纯度
≥98%
通路
Hedgehog
靶点
SMO
产品说明书及文档
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应用领域
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相关材料与文献
技术资料 (2)
文献 (8)
Reagents for developmental regulation of Hedgehog signaling. Methods (San Diego, Calif.) 2014 APR
Abstract
We have examined a number of reagents for their ability to modulate activity of the Hh signaling pathway during embryonic development of Xenopus. In particular we have focused on regulation of events occurring during tailbud stages and later. Two inducible protein reagents based on the Gli1 and Gli3 transcription factors were generated and the activity of these proteins was compared to the Hh signaling pathway inhibitor, cyclopamine, and the activators, Smoothened agonist (SAG) and purmorphamine (PMA). Effectiveness of reagents was assayed using both molecular biological techniques and biological readouts. We found that the small molecule modulators of the Hh pathway were highly specific and effective and produced results generally superior to the more conventional protein reagents for examination of later stage developmental processes.
Hedgehog agonist therapy corrects structural and cognitive deficits in a Down syndrome mouse model. Science translational medicine 2013 SEP
Abstract
Down syndrome (DS) is among the most frequent genetic causes of intellectual disability, and ameliorating this deficit is a major goal in support of people with trisomy 21. The Ts65Dn mouse recapitulates some major brain structural and behavioral phenotypes of DS, including reduced size and cellularity of the cerebellum and learning deficits associated with the hippocampus. We show that a single treatment of newborn mice with the Sonic hedgehog pathway agonist SAG 1.1 (SAG) results in normal cerebellar morphology in adults. Further, SAG treatment at birth rescued phenotypes associated with hippocampal deficits that occur in untreated adult Ts65Dn mice. This treatment resulted in behavioral improvements and normalized performance in the Morris water maze task for learning and memory. SAG treatment also produced physiological effects and partially rescued both N-methyl-d-aspartate (NMDA) receptor-dependent synaptic plasticity and NMDA/AMPA receptor ratio, physiological measures associated with memory. These outcomes confirm an important role for the hedgehog pathway in cerebellar development and raise the possibility for its direct influence in hippocampal function. The positive results from this approach suggest a possible direction for therapeutic intervention to improve cognitive function for this population.
Small molecules greatly improve conversion of human-induced pluripotent stem cells to the neuronal lineage. Stem cells international 2012 JAN
Abstract
Efficient in vitro differentiation into specific cell types is more important than ever after the breakthrough in nuclear reprogramming of somatic cells and its potential for disease modeling and drug screening. Key success factors for neuronal differentiation are the yield of desired neuronal marker expression, reproducibility, length, and cost. Three main neuronal differentiation approaches are stromal-induced neuronal differentiation, embryoid body (EB) differentiation, and direct neuronal differentiation. Here, we describe our neurodifferentiation protocol using small molecules that very efficiently promote neural induction in a 5-stage EB protocol from six induced pluripotent stem cells (iPSC) lines from patients with Parkinson's disease and controls. This protocol generates neural precursors using Dorsomorphin and SB431542 and further maturation into dopaminergic neurons by replacing sonic hedgehog with purmorphamine or smoothened agonist. The advantage of this approach is that all patient-specific iPSC lines tested in this study were successfully and consistently coaxed into the neural lineage.
更多信息
| 种属 | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 912545-86-9 |
| Chemical Formula | C₂₈H₂₈ClN₃OS |
| 纯度 | ≥ 98% |
| Target | SMO |
| Pathway | Hedgehog |
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