产品号 #72052_C
WNT 通路激活剂；抑制 GSK3
总览
CHIR99021 是一种氨基嘧啶衍生物，是一种非常有效的糖原合酶激酶 (GSK) 3 抑制剂，可同时抑制 GSK3β (IC₅₀ = 6.7 nM) 和 GSK3α (IC₅₀ = 10 nM) (Ring et al.)。GSK3 是一种丝氨酸/苏氨酸激酶，是 WNT 通路的关键抑制剂；因此，CHIR99021 可作为 WNT 激活剂发挥作用。它对包括 CDK2 和其他丝氨酸/苏氨酸激酶（例如 MAPK 和 PKB）在内的多种激酶均表现出较低的活性（Bain et al.）。
维持和自我更新
·在没有 LIF 的情况下，与 PD0325901 联合使用可维持小鼠 ES 细胞的未分化状态 （Ying et al.）。
∙与 IWR-1 结合可促进人 ES 细胞和小鼠外胚层干细胞的自我更新（Kim et al.）。
∙与其他小分子结合可从难治性小鼠品系（Kiyonari et al., Ying et al.）和大鼠品系（Li P et al.）中衍生出 ES 细胞。
·与雷帕霉素结合可在无细胞因子条件下维持人和小鼠造血干细胞（Huang et al.）。
·促进小鼠和人肠道干细胞的生长（Wang et al.）。
重编程
·与Forskolin、Tranylcypromine、Valproic Acid、3-Deazaneplanocin A 和 E-616452 结合，可将小鼠胚胎成纤维细胞化学重编程（无遗传因素）为 iPS 细胞（Hou et al.）。
∙使用 OCT4 结合其他小分子促进人体细胞重编程为 iPS 细胞（Zhu et al.）。
∙使用 OCT4 将人 CD34+ 造血细胞转分化为间充质干细胞（Meng et al.）。
·与丙戊酸、RepSox、Forskolin、SP600125、Gö6983 和 Y-27632 结合，将成纤维细胞直接谱系重编程为成熟神经元（Hu et al.）。
·与 Forskolin、ISX-9、SB431542 和 I-BET151 结合，将成纤维细胞直接谱系重编程为成熟神经元（Li et al.）。
·与 PD0325901 和 A 83-01 结合，从人和大鼠体细胞产生 mouse-like 或“ground state” iPS 细胞（Li W et al. 2009）。
分化
·促进人 iPS 细胞向胰岛素分泌细胞分化（Kunisada et al.）。
∙促进人 ES 细胞和 iPS 细胞向心肌细胞分化（Lian et al.）。
∙与 SB431542 和人重组 LIF 结合，从人 ES 细胞生成并维持原始神经干细胞（Li W et al. 2011）。
别名
CT 99021
细胞类型
心肌细胞，PSC衍生，内胚层，PSC衍生，造血干/祖细胞，中胚层，PSC衍生，神经细胞，PSC衍生，神经元，胰腺细胞，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，重编程
研究领域
神经科学，干细胞生物学
CAS 编号
252917-06-9
化学式
C₂₂H₁₈Cl₂N₈
分子量
465.3 克/摩尔
纯度
≥ 95 %
通路
WNT
靶点
GSK3
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 (5)
Publications (15)
Intrinsic Immunity Shapes Viral Resistance of Stem Cells. Cell 2018 JAN
Abstract
Stem cells are highly resistant to viral infection compared to their differentiated progeny; however, the mechanism is mysterious. Here, we analyzed gene expression in mammalian stem cells and cells at various stages of differentiation. We find that, conserved across species, stem cells express a subset of genes previously classified as interferon (IFN) stimulated genes (ISGs) but that expression is intrinsic, as stem cells are refractory to interferon. This intrinsic ISG expression varies in a cell-type-specific manner, and many ISGs decrease upon differentiation, at which time cells become IFN responsive, allowing induction of a broad spectrum of ISGs by IFN signaling. Importantly, we show that intrinsically expressed ISGs protect stem cells against viral infection. We demonstrate the in vivo importance of intrinsic ISG expression for protecting stem cells and their differentiation potential during viral infection. These findings have intriguing implications for understanding stem cell biology and the evolution of pathogen resistance.
Small-Molecule-Driven Direct Reprogramming of Mouse Fibroblasts into Functional Neurons. Cell stem cell 2015 AUG
Abstract
Recently, direct reprogramming between divergent lineages has been achieved by the introduction of regulatory transcription factors. This approach may provide alternative cell resources for drug discovery and regenerative medicine, but applications could be limited by the genetic manipulation involved. Here, we show that mouse fibroblasts can be directly converted into neuronal cells using only a cocktail of small molecules, with a yield of up to textgreater90% being TUJ1-positive after 16 days of induction. After a further maturation stage, these chemically induced neurons (CiNs) possessed neuron-specific expression patterns, generated action potentials, and formed functional synapses. Mechanistically, we found that a BET family bromodomain inhibitor, I-BET151, disrupted the fibroblast-specific program, while the neurogenesis inducer ISX9 was necessary to activate neuron-specific genes. Overall, our findings provide a proof of principle" for chemically induced direct reprogramming of somatic cell fates across germ layers without genetic manipulation�
Direct Conversion of Normal and Alzheimer's Disease Human Fibroblasts into Neuronal Cells by Small Molecules. Cell stem cell 2015 AUG
Abstract
Neuronal conversion from human fibroblasts can be induced by lineage-specific transcription factors; however, the introduction of ectopic genes limits the therapeutic applications of such induced neurons (iNs). Here, we report that human fibroblasts can be directly converted into neuronal cells by a chemical cocktail of seven small molecules, bypassing a neural progenitor stage. These human chemical-induced neuronal cells (hciNs) resembled hiPSC-derived neurons and human iNs (hiNs) with respect to morphology, gene expression profiles, and electrophysiological properties. This approach was further applied to generate hciNs from familial Alzheimer's disease patients. Taken together, our transgene-free and chemical-only approach for direct reprogramming of human fibroblasts into neurons provides an alternative strategy for modeling neurological diseases and for regenerative medicine.
更多信息
| Molecular Weight | 465.3 g/mol |
|---|---|
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
| Alternative Names | CT 99021 |
| Cas Number | 252917-06-9 |
| Chemical Formula | C₂₂H₁₈Cl₂N₈ |
| Purity | ≥ 95% |
| Target | GSK3 |
| Pathway | WNT |
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PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED. FOR ADDITIONAL INFORMATION ON QUALITY AT STEMCELL, REFER TO WWW.STEMCELL.COM/COMPLIANCE.
