GW441756
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.
GW441756是一种TrkA激酶和LRRK2的抑制剂,IC50值分别为320 nM和2 nM[1].
TrkA 激酶的活性可以影响其下游信号,并参与多种生物学过程,包括增殖\分化和凋亡.因此,TrkA 抑制剂可以被开发用于癌症治疗.GW441756属于羟吲哚系列,被发现是一种有效的TrkA抑制剂,对TrkA 也具有选择性,对cRaf1和CDK2的IC50值分别大于12 μM和7 μM.在人肌肉瘤细胞系HTB114中,GW441756可剂量依赖性地抑制肿瘤性增生,诱导细胞凋亡[1,2].
除此之外,GW441756也被发现是一种LRRK2抑制剂.在细胞TR-FRET试验中,GW441756抑制LRRK2的Ser935磷酸化,IC50值为2.2 μM.GW441756并没有表现出明显的细胞毒性,IC50值大于20 μM[3].
参考文献:
[1] Wood E R, Kuyper L, Petrov K G, et al. Discovery and in vitro evaluation of potent TrkA kinase inhibitors: oxindole and aza-oxindoles. Bioorganic & medicinal chemistry letters, 2004, 14(4): 953-957.[2] Montagnoli C, Pistilli A, Stabile A M, et al. Anti-proliferative effects of GW441756, a novel inhibitor of NGFreceptor tyrosine kinase a (TRKA), in human sarcoma. Italian Journal of Anatomy and Embryology, 2010, 115(1/2): 117.
[3] Hermanson S B, Carlson C B, Riddle S M, et al. Screening for novel LRRK2 inhibitors using a high-throughput TR-FRET cellular assay for LRRK2 Ser935 phosphorylation. PloS one, 2012, 7(8): e43580.
Storage | Store at -20°C |
M.Wt | 275.3 |
Cas No. | 504433-23-2 |
Formula | C17H13N3O |
Solubility | insoluble in H2O; insoluble in EtOH; ≥13.75 mg/mL in DMSO |
Chemical Name | (3Z)-3-[(1-methylindol-3-yl)methylidene]-1H-pyrrolo[3,2-b]pyridin-2-one |
SDF | Download SDF |
Canonical SMILES | CN1C=C(C2=CC=CC=C21)C=C3C4=C(C=CC=N4)NC3=O |
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。 |
细胞实验[1]: | |
细胞系 |
人肌肉瘤细胞系HTB114 |
溶解方法 |
该化合物在DMSO中的溶解度>13.8mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
反应条件 |
IC50 = 2nM |
应用 |
在人肌肉瘤细胞系HTB114中,GW441756剂量依赖性地降低肿瘤增殖,并以剂量依赖的方式显著增加细胞凋亡。GW441756也增加了caspase-3的水平,从而导致细胞凋亡。 |
动物实验[2]: | |
动物模型 |
阿尔茨海默病(AD)小鼠模型,PDAPP(J20)小鼠 |
剂量 |
10 mg/kg/day (皮下注射); 5天 |
应用 |
在阿尔茨海默病(AD)小鼠模型,PDAPP(J20)小鼠中,10mg / kg 剂量的GW441756增加sAβPPα的水平,并将sAβPPα与Aβ42的比例增加到对照组的1.85倍。 在这种剂量下,GW441756给出可测量的脑水平,最大脑浓度(Cmax,1h)为1×IC50(50nM)。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。 |
References: [1]. Montagnoli C, Pistilli A, Stabile A M, et al. Anti-proliferative effects of GW441756, a novel inhibitor of NGFreceptor tyrosine kinase a (TRKA), in human sarcoma. Italian Journal of Anatomy and Embryology, 2010, 115(1/2): 117. [2]. Zhang Q#1, Descamps O#1, Hart MJ1, et al. Paradoxical effect of TrkA inhibition in Alzheimer's disease models. J Alzheimers Dis. 2014;40(3):605-617. |
Description | GW441756是一种有效的TrkA选择性抑制剂,IC50值为2 nM. | |||||
靶点 | TrkA | CDK2 | C-Raf-1 | |||
IC50 | 2 nM | >7 μM | >12 μM |
质量控制和MSDS
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