EasySep™小鼠TIL（CD45）正选试剂盒
产品号 #72592_C
激活素/BMP/TGF-β通路抑制剂；抑制ALK5
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总览
LY364947 是 TGFβ/Activin/NODAL 通路的选择性抑制剂，可抑制 ALK5（IC₅₀ = 59 nM）（Sawyer et al.）。LY364947 对 TGFβRII（IC₅₀ = 400 nM）、p38 MAPK（IC₅₀ = 740 nM）和混合谱系激酶 7（MLK-7；IC₅₀ = 1,400 nM）的抑制效果较差 (Li et al., 2006; Sawyer et al.)。
重编程
·与丙戊酸联合使用，可在转导 OCT4、KLF4 和 c-MYC 的小鼠胚胎成纤维细胞重编程中取代 SOX2（Ichida et al.）。
分化
·阻断人间充质干细胞由机械负荷诱导的软骨形成（Li et al., 2010）。
·恢复缺乏Evi-1转录因子的小鼠主动脉旁胸膜细胞的造血潜能（Sato et al.）。
·削弱人胚胎干细胞 (ES) 的定形内胚层分化能力（Jaremko et al.）。
·阻断 TGF-β 诱导的 NMuMg 乳腺上皮细胞或小鼠 ES 细胞衍生内皮细胞的内皮-间质转化 (Peng et al.; Kokudo et al.)。
癌症研究
·抑制用OP-9基质细胞培养的小鼠和人白血病起始细胞的集落形成能力，并且当与伊马替尼联合使用时，降低慢性髓性白血病小鼠模型的致死率（Naka et al.）。
·在基质侵袭试验中降低MDA-MB-231乳腺癌细胞的侵袭性（Shiou et al.）。
细胞类型
癌细胞及细胞系，软骨细胞，内皮细胞，造血干/祖细胞，乳腺细胞，多能干细胞
种属
人，小鼠，非人灵长类，其他物种，大鼠
应用
分化，重编程
研究领域
癌症，干细胞生物学
CAS 编号
396129-53-6
化学式
C₁₇H₁₂N₄
纯度
≥98%
通路
Activin/Nodal/TGFβ
靶点
ALK
产品说明书及文档
请在《产品说明书》中查找相关支持信息和使用说明，或浏览下方更多实验方案。
应用领域
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相关材料与文献
技术资料 (3)
文献 (10)
Synthesis and activity of new aryl- and heteroaryl-substituted pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain.
Journal of medicinal chemistry 2003 SEP
Abstract
Pyrazole-based inhibitors of the transforming growth factor-beta type I receptor kinase domain (TbetaR-I) are described. Examination of the SAR in both enzyme- and cell-based in vitro assays resulted in the emergence of two subseries featuring differing selectivity versus p38 MAP kinase. A common binding mode at the active site has been established by successful cocrystallization and X-ray analysis of potent inhibitors with the TbetaR-I receptor kinase domain.
Kinetic characterization of novel pyrazole TGF-beta receptor I kinase inhibitors and their blockade of the epithelial-mesenchymal transition.
Biochemistry 2005 FEB
Abstract
Transforming growth factor beta (TGF-beta) signaling pathways regulate a wide variety of cellular processes including cell proliferation,differentiation,extracellular matrix deposition,development,and apoptosis. TGF-beta type-I receptor (TbetaRI) is the major receptor that triggers several signaling events by activating downstream targets such as the Smad proteins. The intracellular kinase domain of TbetaRI is essential for its function. In this study,we have identified a short phospho-Smad peptide,pSmad3(-3),KVLTQMGSPSIRCSS(PO4)VS as a substrate of TbetaRI kinase for in vitro kinase assays. This peptide is uniquely phosphorylated by TbetaRI kinase at the C-terminal serine residue,the phosphorylation site of its parent Smad protein in vivo. Specificity analysis demonstrated that the peptide is phosphorylated by only TbetaRI and not TGF-beta type-II receptor kinase,indicating that the peptide is a physiologically relevant substrate suitable for kinetic analysis and screening of TbetaRI kinase inhibitors. Utilizing pSmad3(-3) as a substrate,we have shown that novel pyrazole compounds are potent inhibitors of TbetaRI kinase with K(i) value as low as 15 nM. Kinetic analysis revealed that these pyrazoles act through the ATP-binding site and are typical ATP competitive inhibitors with tight binding kinetics. More importantly,these compounds were shown to inhibit TGF-beta-induced Smad2 phosphorylation in vivo in NMuMg mammary epithelial cells with potency equivalent to the inhibitory activity in the in vitro kinase assay. Cellular selectivity analysis demonstrated that these pyrazoles are capable of inhibiting activin signaling but not bone morphogenic protein or platelet-derived growth factor signal transduction pathways. Further functional analysis revealed that pyrazoles are capable of blocking the TGF-beta-induced epithelial-mesenchymal transition in NMuMg cells,a process involved in the progression of cancer,fibrosis,and other human diseases. These pyrazoles provide a foundation for future development of potent and selective TbetaRI kinase inhibitors to treat human disease.
Dihydropyrrolopyrazole transforming growth factor-beta type I receptor kinase domain inhibitors: a novel benzimidazole series with selectivity versus transforming growth factor-beta type II receptor kinase and mixed lineage kinase-7.
Journal of medicinal chemistry 2006 MAR
Abstract
Novel dihydropyrrolopyrazole-substituted benzimidazoles were synthesized and evaluated in vitro as inhibitors of transforming growth factor-beta type I receptor (TGF-beta RI),TGF-beta RII,and mixed lineage kinase-7 (MLK-7). These compounds were found to be potent TGF-beta RI inhibitors and selective versus TGF-beta RII and MLK-7 kinases. Benzimidazole derivative 8b was active in an in vivo target (TGF-beta RI) inhibition assay.
更多信息
| 物种 | 人, 其它物种, 大鼠, 小鼠, 非人灵长类 |
|---|---|
| Cas Number | 396129-53-6 |
| Chemical Formula | C₁₇H₁₂N₄ |
| 纯度 | ≥ 98% |
| Target | ALK |
| Pathway | Activin/Nodal/TGFβ |
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