NVP-ACC789 (ACC-789)
(Synonyms: N-(3-溴-4-甲基苯基)-4-(4-吡啶甲基)-1-酞嗪胺,ACC-789; ZK202650) 目录号 : GC34126An inhibitor of VEGFRs
Cas No.:300842-64-2
Sample solution is provided at 25 µL, 10mM.
NVP-ACC789 is an inhibitor of VEGF receptor tyrosine kinases (VEGFRs; IC50s = 0.38, 0.02, 0.18, and 0.23 μM for human VEGFR1, 2, 3, and mouse Vegfr2, respectively).1 It is selective for VEGFRs over FGFRs and PDGFRα (IC50s = >10 μM) but has activity at PDGFRβ (IC50 = 1.4 μM) in an enzyme assay. NVP-ACC789 inhibits VEGF-induced VEGFR2 autophosphorylation (IC50 = 11.5 nM in CHO cells transfected with the human receptor). It also inhibits VEGF- and bFGF-induced angiogenesis and cell migration of BAE and BME cells. In vivo, NVP-ACC789 blocks bFGF- and VEGF-induced angiogenesis (ED50s = 9 and 26 mg/kg, respectively) in a mouse model of growth factor-induced angiogenesis.
1.Tille, J.C., Wood, J., Mandriota, S.J., et al.Vascular endothelial growth factor (VEGF) receptor-2 antagonists inhibit VEGF- and basic fibroblast growth factor-induced angiogenesis in vivo and in vitroJ. Pharmacol. Exp. Ther.299(3)1073-1085(2001)
Kinase experiment: | Human VEGFR-2-transfected CHO cells are seeded into 6-well plates and grown to about 80% confluency. NVP-ACC789 is added in serial dilutions and the cells incubated for 2 h at 37°C in medium without fetal calf serum (FCS). VEGF (20 ng/mL) is then added. After a 5-min incubation at 37°C, the cells are washed twice with ice-cold phosphate-buffered saline and lysed. Nuclei are removed by centrifugation for 10 min at 4°C. Protein concentrations of the lysates are determined[1]. |
Cell experiment: | HUVE cell proliferation is determined. Cells are seeded into 1.5% gelatin-coated 96-well plates (5×103 cells per well) and incubated in endothelial cell growth medium containing 5% fetal calf serum (FCS) for 24 h. The medium is replaced with essential basic medium (1.5% FCS), and the cells are incubated for another 24 h. Essential basic medium is then replaced with fresh medium containing either 50 ng/mL VEGF or 0.5 ng/mL bFGF. NVP-ACC789 is added just before addition of growth factors. The cells are incubated for a further 24 h before adding the BrdU labeling solution. Twenty four hours later, the labeling solution is removed, the cells are fixed, and the incorporated BrdU is visualized with a peroxidase-labeled anti-BrdU antibody and TMB substrate[1]. |
Animal experiment: | Porous Teflon chambers (volume, 0.5 mL) filled with 0.8% w/v agar-containing heparin (20 U/mL) with or without VEGF (2 μg/mL) or bFGF (0.3 μg/mL) are implanted subcutaneously on the dorsal flank of female mice. The mice are treated with NVP-ACC789 (p.o. once daily) or vehicle (5% dimethyl sulfoxide, 1% Tween 80 in water) starting 1 day before implantation of the chamber and continuing for 5 days thereafter. At the end of the treatment period, the mice are killed, and the chambers are removed. The vascularized tissue growing around the chamber is removed carefully and weighed, and the blood content is assessed by measuring hemoglobin levels. The percentage inhibition of the angiogenic response (increase in tissue weight or total blood) is calculated. EC50 values are estimated from the dose response curves (% inhibition versus dose). Each experiment is performed with six animals per dose group and each dose is tested in at least two independent experiments[1]. |
References: [1]. Tille JC, et al. Vascular endothelial growth factor (VEGF) receptor-2 antagonists inhibit VEGF- and basicfibroblast growth factor-induced angiogenesis in vivo and in vitro. J Pharmacol Exp Ther. 2001 Dec;299(3):1073-85. |
Cas No. | 300842-64-2 | SDF | |
别名 | N-(3-溴-4-甲基苯基)-4-(4-吡啶甲基)-1-酞嗪胺,ACC-789; ZK202650 | ||
Canonical SMILES | CC1=CC=C(NC2=NN=C(CC3=CC=NC=C3)C4=C2C=CC=C4)C=C1Br | ||
分子式 | C21H17BrN4 | 分子量 | 405.29 |
溶解度 | DMSO : 60 mg/mL (148.04 mM) | 储存条件 | Store at -20°C |
General tips | 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 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。 为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。 |
||
Shipping Condition | 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。 |
制备储备液 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 2.4674 mL | 12.3368 mL | 24.6737 mL |
5 mM | 0.4935 mL | 2.4674 mL | 4.9347 mL |
10 mM | 0.2467 mL | 1.2337 mL | 2.4674 mL |
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量) | ||||||||||
给药剂量 | mg/kg | 动物平均体重 | g | 每只动物给药体积 | ul | 动物数量 | 只 | |||
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方) | ||||||||||
% DMSO % % Tween 80 % saline | ||||||||||
计算重置 |
计算结果:
工作液浓度: mg/ml;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL,
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL saline,混匀澄清。
1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet