E-3810 |
Catalog No.GC12149
One-Click Copy Product Info
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Products are for research use only. Not for human use. We do not sell to patients.
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 | |
| Chemical Name | 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 | ||
| Formula | C26H25N3O4 | M.Wt | 443.49 |
| Solubility | Soluble in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2548 mL | 11.2742 mL | 22.5484 mL |
| 5 mM | 451 μL | 2.2548 mL | 4.5097 mL |
| 10 mM | 225.5 μL | 1.1274 mL | 2.2548 mL |
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)