(Z)-Semaxanib

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Chemical Structure| 194413-58-6 同义名 : (Z)-SU5416
CAS号 : 194413-58-6
货号 : A204179
分子式 : C15H14N2O
纯度 : 99+%
分子量 : 238.28
MDL号 : MFCD09763655
存储条件：

Pure form Sealed in dry, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：

5% DMSO+40%PEG 300+ 5% Tween80 + water 0.5 mg/mL

生物活性
描述 Vascular endothelial growth factor (VEGF) plays a prosurvival and antiapoptotic role in endothelial cells. Z-Semaxanib (SU5416) is the first VEGF receptor 2 inhibitor to enter clinical development for cancer therapy[3]. SU5416 directly inhibited VEGF-mediated ERK phosphorylation, cell proliferation, and Kdr transcription, but not Matrigel tube formation in primary murine cardiac endothelial cells in vitro. SU5416 did not inhibit chronic hypoxia (CH-PH) induced Right ventricular(RV) angiogenesis, endothelial cell proliferation, or RV hypertrophy in vivo, despite significantly altering the expression profile of genes involved in angiogenesis[4]. The combination of radiation and SU5416 significantly inhibited cell survival, the repair of radiation-induced DNA damage, and induced apoptosis. It also caused cell cycle arrest, inhibited cell migration and invasion, and suppressed angiogenesis[5]. SU5416 inhibited VEGF expression at the transcriptional level through the HIF-1 DNA binding site. HIF-1 is composed of HIF-1alpha and HIF-1beta subunits. SU5416 specifically decreased HIF-1alpha, but not HIF-1beta protein levels, it inhibited VEGF and HIF-1alpha expression through the inhibition of PI3K/AKT/p70S6K1 pathway in ovarian cancer cells[6]. SU5416 potently activated AhR-dependent reporter genes, induced AhR nuclear localization, facilitated AhR-DNA binding, and increased, expression of its endogenous target genes. SU5416 significantly inhibited proliferation of Hepa1 hepatoma cells in an AhR-dependent manner, but did not induce apoptosis. SU5416 also inhibited the growth of human HepG2 liver cancer cells[7].
细胞研究
细胞系 浓度 检测类型 检测时间 活性说明 数据源
A431 cells Function assay Inhibition of VEGFR2 expressed in human A431 cells, IC50=12.9 μM 20558072
CHO cells Function assay Inhibition of VEGFR induced autophosphorylation of human Vascular endothelial growth factor receptor 2 (VEGFR2) transfected in CHO cells, IC50=0.884 μM 12477352
human A431 cells Function assay Antiangiogenic activity against human A431 cells, IC50=0.085 μM 20403693
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

4.20mL

0.84mL

0.42mL

20.98mL

4.20mL

2.10mL

41.97mL

8.39mL

4.20mL
参考文献

[1]Fong TA, Shawver LK, et al. 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 Jan 1;59(1):99-106.

[2]Vajkoczy P, Menger MD, et al. Inhibition of tumor growth, angiogenesis, and microcirculation by the novel Flk-1 inhibitor SU5416 as assessed by intravital multi-fluorescence videomicroscopy. Neoplasia. 1999 Apr;1(1):31-41. Erratum in: Neoplasia 1999 Jun;1(2):183.

[3]Seiichiro Sakao,et al. The effects of antiangiogenic compound SU5416 in a rat model of pulmonary arterial hypertension. Respiration. 2011;81(3):253-61.

[4]Grace L Peloquin,et al. SU5416 does not attenuate early RV angiogenesis in the murine chronic hypoxia PH model . Respir Res.2019 Jun 17;20(1):123.

[5]Eun Ho Kim,et al. Mechanisms for SU5416 as a radiosensitizer of endothelial cells. Int J Oncol. 2015 Oct;47(4):1440-50.

[6]Xiao-Song Zhong,et al. SU5416 inhibited VEGF and HIF-1alpha expression through the PI3K/AKT/p70S6K1 signaling pathway. Biochem Biophys Res Commun. 2004 Nov 12;324(2):471-80.

[7]Edmond F O'Donnell ,et al. The aryl hydrocarbon receptor is required for induction of p21cip1/waf1 expression and growth inhibition by SU5416 in hepatoma cells. Oncotarget.2017 Apr 11;8(15):25211-25225.