LY364947
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
多功能细胞因子转化生长因子β(TGF-β)属于生长因子大家庭的成员,参与调节多种生物学过程,包括细胞生长和分化\基质调节和胚胎发育.LY364947是一种转化生长因子β I型受体激酶结构域的抑制剂.
体外试验:LY364947被认为是有效的抑制剂(IC50 = 51 nM),并且被选为SAR研究的平台.该化合物被进一步评估作为水貂肺癌细胞(p3TP Lux)TGF-β依赖的荧光素酶产生的抑制剂以及小鼠成纤维细胞(NIH 3T3)生长的抑制剂[1].
体内试验:在NMDA诱导的视网膜变性大鼠模型中,同时注射NMDA和TGF-β抑制剂LY364947,可轻微但明显地减弱神经节细胞层细胞数量的减少,并且几乎完全预防毛细血管退化的增强[3].
临床试验:到目前为止,LY364947仍处于临床研究阶段.
参考文献:
[1] Sawyer JS, Anderson BD, Beight DW, Campbell RM, Jones ML, Herron DK, Lampe JW, McCowan JR, McMillen WT, Mort N, Parsons S, Smith EC, Vieth M, Weir LC, Yan L, Zhang F, Yingling JM. Synthesis and activity of new aryl- and heteroaryl-substituted pyrazole inhibitors of the transforming growth factor-beta type I receptor kinase domain. J Med Chem. 2003 Sep 11;46(19):3953-6.
[2] Ueda K, Nakahara T, Mori A, Sakamoto K, Ishii K. Protective effects of TGF-β inhibitors in a rat model of NMDA-induced retinal degeneration. Eur J Pharmacol. 2013 Jan 15;699(1-3):188-93.
- 1. Tongde Wu, Xinhua Li, et al. "Krüppel like factor 10 prevents intervertebral disc degeneration via TGF-β signaling pathway both in vitro and in vivo." J Orthop Translat. 2021 May 15;29:19-29. PMID:34094855
- 2. Meizhong Peng, Meiling Yang, et al. "Huoxin Pill inhibits isoproterenol-induced transdifferentiation and collagen synthesis in cardiac fibroblasts through the TGF-β/Smads pathway." J Ethnopharmacol. 2021 Jul 15;275:114061. PMID:33892065
- 3. Lin B, Coleman JH, et al. "Injury Induces Endogenous Reprogramming and Dedifferentiation of Neuronal Progenitors to Multipotency." Cell Stem Cell. 2017 Nov 20. pii: S1934-5909(17)30375-2. PMID:29174332
Storage | Store at -20°C |
M.Wt | 272.3 |
Cas No. | 396129-53-6 |
Formula | C17H12N4 |
Solubility | insoluble in EtOH; insoluble in H2O; ≥24.4 mg/mL in DMSO |
Chemical Name | 4-(5-pyridin-2-yl-1H-pyrazol-4-yl)quinoline |
SDF | Download SDF |
Canonical SMILES | C1=CC=C2C(=C1)C(=CC=N2)C3=C(NN=C3)C4=CC=CC=N4 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
激酶实验 [1]: | |
过滤-结合试验 |
在不同酶浓度下,通过过滤-结合试验测定LY364947 IC50值。反应体系总体积为40 μL。反应体系含50 mM HEPES,pH 7.5,1 mM NaF,200 μM pKSmad3(-3),50 mM ATP以及抑制剂浓度为1600、800、400、200、100、50、25和0 nM的抑制剂,将其置于在30 °C下孵育30分钟。通过GraphPad Prism软件,使用非线性回归法计算其IC50值。通过绘制酶浓度与IC50值的相关性图来确定结合类型。 |
细胞实验 [2]: | |
细胞系 |
HOXB9-MCF10A细胞 |
制备方法 |
在DMSO中的溶解度有限。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。 |
反应条件 |
10 μM;24小时 |
实验结果 |
在HOXB9-MCF10A细胞中,LY364947抑制TGF-β活化,从而抑制Smad2磷酸化,同时,不影响TGF-β1和TGF-β2表达。此外,LY364947改变上皮细胞形态,使E-钙粘蛋白再表达,并抑制纤连蛋白和波形蛋白。此外,LY364947减少HOXB9-MCF10A细胞的迁移与侵袭。 |
动物实验 [3]: | |
动物模型 |
NMDA诱导的视网膜变性大鼠模型 |
给药剂量 |
50 nM;5μL;玻璃体内注射 |
实验结果 |
在NMDA诱导的视网膜变性大鼠模型中,LY364947显著抑制NMDA诱导的神经节细胞层中的细胞损失。此外,LY364947显著防止NMDA诱导的视网膜损伤。此外,同时给予NMDA和LY364947不会改变NG2阳性周细胞的形态。 |
注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。 |
References: [1]. Peng SB, Yan L, Xia X, Watkins SA, Brooks HB, Beight D, Herron DK, Jones ML, Lampe JW, McMillen WT, Mort N, Sawyer JS, Yingling JM. Kinetic characterization of novel pyrazole TGF-beta receptor I kinase inhibitors and their blockade of the epithelial-mesenchymal transition. Biochemistry. 2005 Feb 22;44(7):2293-304. [2]. Hayashida T, Takahashi F, Chiba N, Brachtel E, Takahashi M, Godin-Heymann N, Gross KW, Vivanco Md, Wijendran V, Shioda T, Sgroi D, Donahoe PK, Maheswaran S. HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis. Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1100-5. [3]. Ueda K, Nakahara T, Mori A, Sakamoto K, Ishii K. Protective effects of TGF-β inhibitors in a rat model of NMDA-induced retinal degeneration. Eur J Pharmacol. 2013 Jan 15;699(1-3):188-93. |
质量控制和MSDS
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