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GNF-5837

现货
Catalog No.
A8303
Pan-Trk抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 950.00
现货
10mg
¥ 1,030.00
现货
50mg
¥ 2,780.00
现货
200mg
¥ 6,700.00
Ship with 10-15 days

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Background

IC50: A potent and selective pan-TRK inhibitor, suppressing the activity of TrkA and TrkB with IC50 of 8 and 12 nM, respectively.

GNF-5837 is reported to selectively suppress pan-TRK potently in an oral-bioavailable manner. Neurotrophins and their receptors (TRKs) are important in malignant transformations, chemotaxis, metastasis, and survival signaling and may contribute to the pathogenesis of a variety of tumors. The TRK-inhibiting properties of GNF-5837 therefore make it a useful tool to investigate TRK biology in cancer and other non-oncology indications. [1]

In vitro: The anti-TRKA activity of GNF-5837 was detected in Ba/F3 and RIE cells expressing both TRKA and NGF. In Ba/F3 cells, this compound exhibited intensively anti-proliferation activity with an IC50 of 0.042 μM. RIE cells expressing TRKA and NGF could only survive under low attachment condition and were resistant to detachment-induced apoptosis. GNF-5837 seemed to suppress cell growth and proliferation of RIE cells intensively with an IC50 of 0.017 μM. Moreover, GNF-5837 is reported to show inhibitory effects on c-Kit and PDGFR in Mo7e cells and Rat-A10 cells, respectively. [1]

In vivo: Mice models with tumor xenografts derived from RIE cells expressing both TRKA and NGF were established in one study. GNF-5837 was then administered at ascending doses once daily to these mice for 10 days, with the aim to investigate the in vivo efficacy of GNF-5837. 72 and 100% tumor inhibition was reported at the dose of 50 and 100 mg/kg, respectively. At 25 mg/kg, only partial tumor growth inhibition was observed. [1]

Clinical trial: So far, no clinical trial has been conducted.

Reference:
[1] Albaugh F, Fan Y, Mi Y, Sun FX, Adrian F, Li NX, Jia Y, Sarkisova Y, Kreusch A, Hood T, Lu M, Liu GX, Huang SL, Liu ZS, Loren J, Tuntland T, Karanewsky DS, Seidel HM and Molteni V.  Discovery of GNF-5837, a selective TRK inhibitor with efficacy in rodent cancer tumor models. ACS Med. Chem. Lett. 2012. 3: 1405.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt535.49
Cas No.1033769-28-6
FormulaC28H21F4N5O2
Solubility≥17mg/mL in DMSO, <2 mg/mL in EtOH, <2 mg/mL in H2O
Chemical Name(Z)-1-(3-((3-((1H-pyrrol-2-yl)methylene)-2-oxoindolin-6-yl)amino)-4-methylphenyl)-3-(2-fluoro-5-(trifluoromethyl)phenyl)urea
SDFDownload SDF
Canonical SMILESO=C(NC1=CC(C(F)(F)F)=CC=C1F)NC2=CC=C(C)C(NC3=CC(NC/4=O)=C(C=C3)C4=C\C5=CC=CN5)=C2
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。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。

试验操作

细胞实验 [1]:

细胞系

表达TRKA和NGF的Ba/F3和RIE细胞

制备方法

在DMSO中的溶解度大于17 mg/mL。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

0.17 nM ~ 10 uM;48小时

实验结果

在表达TRKA和NGF的Ba/F3细胞中,GNF-5837显示有效的抗增殖活性,其IC50值为0.042 μM。然而,在亲代Ba/F3细胞中,GNF-5837在10 μM的剂量下也不显示抗增殖活性。此外,GNF-5837也可以显著抑制表达TRKA和NGF的RIE细胞的细胞生长与增殖,其IC50值为0.017 μM。

动物实验 [1]:

动物模型

Rie-TRKAmNGF异种移植小鼠模型

给药剂量

25、50或100 mg/kg;口服给药;每天1次,持续10天

实验结果

于10天治疗后,50 mg/kg和100 mg/kg治疗组中的小鼠分别出现72%和100%的肿瘤消退。在25 mg/kg的剂量下,GNF-5837仅部分抑制Rie-TRKAmNGF异种移植小鼠模型的肿瘤生长。

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]. Albaugh P, Fan Y, Mi Y, Sun FX, Adrian F, Li NX, Jia Y, Sarkisova Y, Kreusch A, Hood T, Lu M, Liu GX, Huang SL, Liu ZS, Loren J, Tuntland T, Karanewsky DS, Seidel HM and Molteni V. Discovery of GNF-5837, a selective TRK inhibitor with efficacy in rodent cancer tumor models. ACS Med. Chem. Lett. 2012. 3: 1405.

质量控制

化学结构

GNF-5837