SU1498 (AG 1498) is a selective inhibitor of the VEGFR2; inhibits Flk-1 with an IC₅₀ of value of 700 nM^[1].

SU1498 stimulates accumulation of phosphorylated ERKs in human umbilical vein endothelial cells and in human aortic endothelial cells in a manner that is dependent on the functioning of the upstream components of the MAPK pathway, B-Raf, and MEK kinases. The enhanced accumulation of phospho-ERKs is observed only in cells that have been stimulated with sphingosine 1-phosphate or protein growth factors; SU1498 by itself is ineffective^[2]. SU1498 blocks signal transduction from VEGFR2 in MS1 VEGF cells.In the presence of SU1498, levels of Ets-1 are decreased, suggesting that VEGF-VEGFR-2 interactions contributed to baseline levels of Ets-1 expression, and interruption of this autocrine interaction with SU1498 led to decreased expression of Ets-1^[3]. SU1498 treatment significantly impacts U87 cell proliferation and apoptosis. SU1498 induces a marked increase in lipids and a decrease in glycerophosphocholine. Accordingly, accumulation of lipid droplets is seen in the cytoplasm of SU1498-treated U87 cells^[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

390.52

C₂₅H₃₀N₂O₂

168835-82-3

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : 100 mg/mL (256.07 mM; Need ultrasonic)

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (6.40 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.40 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: 2.5 mg/mL (6.40 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (6.40 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明

• [1]. Strawn LM, et al. Flk-1 as a target for tumor growth inhibition.Cancer Res. 1996 Aug 1;56(15):3540-5.

  [2]. Boguslawski G, et al. SU1498, an inhibitor of vascular endothelial growth factor receptor 2, causes accumulation of phosphorylated ERK kinases and inhibits their activity in vivo and in vitro.J Biol Chem. 2004 Feb 13;279(7):5716-24.

  [3]. Arbiser JL, et al. Overexpression of VEGF 121 in immortalized endothelial cells causes conversion to slowly growing angiosarcoma and high level expression of the VEGF receptors VEGFR-1 and VEGFR-2 in vivo.Am J Pathol. 2000 Apr;156(4):1469-76.

  [4]. Mesti T, et al. Metabolic impact of anti-angiogenic agents on U87 glioma cells.PLoS One. 2014 Jun 12;9(6):e99198.

The ERK1 or ERK2 solution is pipetted into tubes (1 μL per tube) and mixed with 0-10 μL of 50 μM SU1498 (in kinase buffer without ATP). The blank tube receives buffer only. The volume is adjusted to 11 μL with the same buffer, and the mixtures are incubated for 10 min at 25°C. This is followed by the addition of 40 μL of the Elk1-ATP-buffer solution, and the incubations are continued for 30 min at 30°C. The reactions are stopped with 20 μL of 4× sample buffer mix and heating at 95°C for 10 min. Samples (15 μL) are fractionated by SDS-PAGE, and phosphorylated Elk1 is detected by immunoblotting with anti-phospho-Elk1 antibody^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

For cell proliferation assay, U87 cells are seeded in 24-well plates (30,000 cells/well) and allowed to attach overnight. Cells are then treated for 24 or 72 h with different concentrations of Bevacizumab (from 10 ng/mL to 250 µg/mL) or SU1498 (from 1 µM to 30 µM) in triplicate wells. The cell viability is then assessed with the MTT assay^[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Strawn LM, et al. Flk-1 as a target for tumor growth inhibition.Cancer Res. 1996 Aug 1;56(15):3540-5.

  [2]. Boguslawski G, et al. SU1498, an inhibitor of vascular endothelial growth factor receptor 2, causes accumulation of phosphorylated ERK kinases and inhibits their activity in vivo and in vitro.J Biol Chem. 2004 Feb 13;279(7):5716-24.

  [3]. Arbiser JL, et al. Overexpression of VEGF 121 in immortalized endothelial cells causes conversion to slowly growing angiosarcoma and high level expression of the VEGF receptors VEGFR-1 and VEGFR-2 in vivo.Am J Pathol. 2000 Apr;156(4):1469-76.

  [4]. Mesti T, et al. Metabolic impact of anti-angiogenic agents on U87 glioma cells.PLoS One. 2014 Jun 12;9(6):e99198.