E-3810
(Synonyms: 德立替尼; E-3810) 目录号 : GC12149
E-3810 (E-3810) 是一种新型的 VEGFR 和 FGFR 双重抑制剂，有效且选择性地抑制 VEGFR1、VEGFR2、VEGFR3、FGFR1 和 FGFR2，IC50 为 7 nM、25 nM、10 nM、17.5 nM 和 82.5 nM，分别。
Cas No.:1058137-23-7
Sample solution is provided at 25 µL, 10mM.
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E-3810 is a small-molecule dual inhibitor of VEGF and FGF receptors with IC 50 values of 7, 25, 10, 17.5, 82.5 and 237.5 nM for VEGFR-1, 2, 3, FGFR-1, 2 and 3, respectively [1].
The vascular endothelial growthfactor (VEGF) and fibroblast growth factor (FGF) are important factors in angiogenesis. They promote the process of angiogenesis through binding to their associated tyrosine kinase receptors and trigger a cascade signaling pathway that finally leads to the increased proliferation of the blood vessel cells and permeability of the vessels. Tumor cells are rapidly proliferating cells which need more vessels to deliver nutrients, therefore VEGFR and FGFR are attractive targets in antitumor treatment. As a selective inhibitor of VEGFR and FGFR, E-3810 shows potent effects in both in vitro and in vivo assays [1].
E-3810 exerted potent inhibition effects on all the three receptors of VEGFR family and two members (FGFR-1 and 2) of FGFR family in MTS assay. It also had effects on colony stimulating factor (CSF)-1R with IC50 value of 5 nM. When treated with human umbelical vein cells (HUVEC), E-3810 significantly inhibited cell proliferation induced by the addition of VEGF and bFGF with IC50 values of 40 and 50 nM, respectively. In NIH3T3 cells, E-3810 showed no inhibitory efficacy on PDGFR until the concentration of it was up to μM range, demonstrating the selectivity of E-3810 [1].
In the mice model, oral administration of 20 mg/kg E-3810 for 7 days significantly inhibited vessel formation induced by bFGF. E-3810 also exerted effective inhibition on tumor growth in variety of human tumor xenografts such as A498, HT29 and A2780. Besides that, it was reported that the combination treatment of E-3810 and paclitaxel showed higher antitumor activity than that of paclitaxel with brivanib or sunitinib in the MDA-MB-231 breast cancer xenografts [1, 2].
References:
[1]. Bello E, Colella G, Scarlato V, et al. E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer research, 2011, 71(4): 1396-1405.
[2]. Bello E, Taraboletti G, Colella G, et al. The tyrosine kinase inhibitor E-3810 combined with paclitaxel inhibits the growth of advanced-stage triple-negative breast cancer xenografts. Molecular cancer therapeutics, 2013, 12(2): 131-140.
Cell experiment: | Exponentially growing HUVEC or NHI3T3 cells are seeded into 96-well plates at a density of 3 to 6×103 cells/100 μL/well in complete medium. In the experiments without serum starvation, 24 hours after seeding, cells are exposed to different Lucitanib (E-3810) concentrations without or with VEGF165 (50 ng/mL) or bFGF (20 ng/mL) ligands and the antiproliferative effect of the drugs is evaluated after 72 hours by MTS Colorimetric Assay. In the assays with serum starvation conditions, 24 hours after seeding complete medium is removed and after 3 rounds of washing with PBS, cells are cultured in medium containing 1% BSA. After 18 to 24 hours, cells are processed. Exponentially growing A2780, A498, SN12KI, and HepG2 cells are seeded into 96-well plates at 3 to 5×103 cells/100 μL/well in complete medium. Twenty-four hours later cells are treated with different drug concentrations for 72 hours and the antiproliferative effect is evaluated by MTS[1]. |
Animal experiment: | Mice[3] MDA-MB-231 tumor-bearing mice are randomized when their tumor masses are about 350 to 400 mg to receive Lucitanib (E-3810) (15 mg/kg), Brivanib, and Sunitinib at the doses used for the antitumor activity trial, for 10 days. Four hours after the antiangiogenic dose of day 7, Paclitaxel is injected intravenously at the dose of 20 mg/kg and tumor and plasma samples are collected after 1, 4, and 24 hours in all the groups (each group consisting of 3 animals). At the indicated sampling time, mice are anesthetized, blood is collected from the retro-orbital plexus into heparinized tubes, and the plasma fraction is separated. Mice are killed by cervical dislocation, and tumors excised and snap-frozen. The samples are analyzed by high-performance liquid chromatography (HPLC) with UV detection at 230 nm. |
References: [1]. Bello E, et al. E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405. | |
| Cas No. | 1058137-23-7 | SDF | |
| 别名 | 德立替尼; E-3810 | ||
| 化学名 | 6-[7-[(1-aminocyclopropyl)methoxy]-6-methoxyquinolin-4-yl]oxy-N-methylnaphthalene-1-carboxamide | ||
| Canonical SMILES | CNC(=O)C1=CC=CC2=C1C=CC(=C2)OC3=C4C=C(C(=CC4=NC=C3)OCC5(CC5)N)OC | ||
| 分子式 | C26H25N3O4 | 分子量 | 443.49 |
| 溶解度 | Soluble in DMSO | 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。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2548 mL | 11.2742 mL | 22.5484 mL |
| 5 mM | 0.451 mL | 2.2548 mL | 4.5097 mL |
| 10 mM | 0.2255 mL | 1.1274 mL | 2.2548 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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