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SU5416

现货
Catalog No.
A3847
VEGF受体抑制剂和AHR激动剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 600.00
现货
10mg
¥ 700.00
现货
50mg
¥ 1,900.00
现货
100mg
¥ 2,500.00
现货

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Background

Description: SU5416 was found to inhibit VEGF-dependent phosphorylation of the Flk-1 receptor in Flk-1-overexpressing NIH 3T3 cells with an IC50 of 1.04±0.53 mM
Vascular endothelial growth factor (VEGF), which stimulates vasculogenesis and angiogenesis, is able to create new blood vessels during embryonic development, new blood vessels after injury, muscle following exercise, and new vessels (collateral circulation) to bypass blocked vessels. Semaxanib (SU5416), a tyrosine-kinase inhibitor drug designed by SUGEN as a cancer therapeutic, is a potent and selective synthetic inhibitor of the Flk-1/KDR VEGF receptor tyrosine kinase demonstrating antiangiogenic effects.
Preclinical study: SU5416 was found to inhibit vascular endothelial growth factor-dependent mitogenesis of human endothelial cells. Moreover, systemic administration of SU5416 at nontoxic doses in mice resulted in the inhibition of subcutaneous tumor growth of cells derived from various tissue origins. The antitumor effect of SU5416 was accompanied by the appearance of pale white tumors, supporting its antiangiogenic property [1].
Another study showed that SU5416 was also an aryl hydrocarbon receptor (AHR) agonist with unique properties. Like TCDD, SU5416 favors induction of indoleamine 2,3 dioxygenase (IDO) in immunologically relevant populations such as dendritic cells in an AHR-dependent manner, leading to generation of regulatory T-cells in vitro. These characteristics lead us to suggest that SU5416 may be an ideal clinical agent for treatment of autoimmune diseases and prevention of transplant rejection, two areas where regulatory ligands of the AHR have shown promise [2].
Clinical trial: As an anticancer agent, SU5416 went as far as Phase III clinical trials, but showed poor results. Its clical termination is based on the results from a planned interim efficacy and safety analyses of a large phase III study of standard chemotherapy with or without SU5416 in the treatment of patients with advanced stage colorectal cancer, which shows that the study will not achieve the defined trial  endpoints due to a lack of clinical benefit.
References:
[1] Fong TA, Shawver LK, Sun L, Tang C, App H, Powell TJ, Kim YH, Schreck R, Wang X, Risau W, Ullrich A, Hirth KP, McMahon G. SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res. 1999;59(1):99-106.
[2] Mezrich JD, Nguyen LP, Kennedy G, Nukaya M, Fechner JH, Zhang X, Xing Y, Bradfield CA. SU5416, a VEGF receptor inhibitor and ligand of the AHR, represents a new alternative for immunomodulation. PLoS One. 2012;7(9):e44547. doi: 10.1371/journal.pone.0044547.

Chemical Properties

Physical AppearanceA solid
StorageDesiccate at -20°C
M.Wt238.28
Cas No.204005-46-9
FormulaC15H14N2O
SynonymsSemaxinib;SU-5416;SU 5416
Solubility≥11.9 mg/mL in DMSO, <2.28 mg/mL in EtOH, <2.38 mg/mL in H2O
Chemical Name(3Z)-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one
SDFDownload SDF
Canonical SMILESCC1=CC(=C(N1)C=C2C3=CC=CC=C3NC2=O)C
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

HUVECs

制备方法

在DMSO中的溶解度大于11.9 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

0.01 ~ 100 μM;2天

实验结果

在HUVECs中,SU5416呈剂量依赖性地抑制VEGF和FGF诱导的有丝分裂,其IC50值分别为0.04 ± 0.02 μM和50 μM。与FGF诱导的有丝分裂相比,SU5416对VEGF诱导的有丝分裂显示出> 1000倍的选择性抑制作用。

动物实验 [1]:

动物模型

携带A375细胞异种移植瘤的雌性BALB/c裸鼠

给药剂量

1 ~ 25 mg/kg;腹腔注射;每天1次,持续39天

实验结果

在携带A375细胞异种移植瘤的BALB/c裸鼠中,SU5416 (3 mg/kg/day) 显著抑制肿瘤生长。在25 mg/kg/day的剂量下,SU5416抑制> 85%的肿瘤生长,同时,没有导致小鼠死亡。

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]. Fong TA, Shawver LK, Sun L, Tang C, App H, Powell TJ, Kim YH, Schreck R, Wang X, Risau W, Ullrich A, Hirth KP, McMahon G. SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res. 1999;59(1):99-106.

生物活性

Description Semaxanib (SU5416)是一种有效的选择性VEGFR(Flk-1/KDR)抑制剂,IC50值为1.23 μM。
靶点 VEGFR          
IC50 1.23 μM          

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