产品号 #73792_C
激活素/Nodal/TGF-β通路抑制剂；抑制ALK5
总览
RepSox是一种可渗透细胞的TGF-β 1型受体（TGF-β RI） ALK5选择性抑制剂（IC₅₀= 4、18和23 nM），分别用于ALK5自磷酸化，TGF-β细胞测定和ALK5在HepG2细胞中的结合；Gellibert et al.)。该抑制剂对9种相关激酶的活性较低（IC₅₀ > 16µM），包括p38 MAPK和GSK3 （Gellibert et al.）。
重编程
·增强用OCT4、KLF4和c-MYC转导的小鼠胚胎成纤维细胞（MEF）的重编程（Ichida et al.; Subramanyam et al.）。
·结合CHIR99021、丙戊酸、Forskolin、SP600125、Gö6983和Y-27632，将成纤维细胞直接谱系重编程为成熟神经元（Hu et al.）。
分化
·单独或联合福斯克林、地塞米松和烟酰胺可诱导人胰腺祖细胞分化为胰岛素生成细胞（Kunisada et al.; Rezania et al.）。
细胞类型
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，重编程
研究领域
干细胞生物学
CAS 编号
446859-33-2
化学式
C₁₇H₁₃N₅
纯度
≥98%
通路
Activin/Nodal/TGFβ
靶点
ALK5
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Resources and Publications
Publications (3)
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.
A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog. Cell stem cell 2009 NOV
Abstract
The combined activity of three transcription factors can reprogram adult cells into induced pluripotent stem cells (iPSCs). However, the transgenic methods used for delivering reprogramming factors have raised concerns regarding the future utility of the resulting stem cells. These uncertainties could be overcome if each transgenic factor were replaced with a small molecule that either directly activated its expression from the somatic genome or in some way compensated for its activity. To this end, we have used high-content chemical screening to identify small molecules that can replace Sox2 in reprogramming. We show that one of these molecules functions in reprogramming by inhibiting Tgf-beta signaling in a stable and trapped intermediate cell type that forms during the process. We find that this inhibition promotes the completion of reprogramming through induction of the transcription factor Nanog.
Identification of 1,5-naphthyridine derivatives as a novel series of potent and selective TGF-beta type I receptor inhibitors. Journal of medicinal chemistry 2004 AUG
Abstract
Optimization of the screening hit 1 led to the identification of novel 1,5-naphthyridine aminothiazole and pyrazole derivatives, which are potent and selective inhibitors of the transforming growth factor-beta type I receptor, ALK5. Compounds 15 and 19, which inhibited ALK5 autophosphorylation with IC50 = 6 and 4 nM, respectively, showed potent activities in both binding and cellular assays and exhibited selectivity over p38 mitogen-activated protein kinase. The X-ray crystal structure of 19 in complex with human ALK5 is described, confirming the binding mode proposed from docking studies.
更多信息
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 446859-33-2 |
| Chemical Formula | C₁₇H₁₃N₅ |
| Purity | ≥ 98% |
| Target | ALK5 |
| Pathway | Activin/Nodal/TGFβ |
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