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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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Purity: ≥98%
Lucitanib (formerly E3810; AL3810; E-3810) is a novel and potent dual VEGFR and FGFR inhibitor with anticancer effects. It has inhibitory concentrations of 7 nM, 25 nM, 10 nM, 17.5 nM, and 82.5 nM for human vascular endothelial growth factor receptors, including VEGFR1, VEGFR2, VEGFR3, FGFR1, and FGFR2. In the nanometer range, lucitanib inhibits the kinases of VEGFR-1, -2, -3 and FGFR-1, -2. This may lead to the induction of tumor cell death and the inhibition of tumor angiogenesis and proliferation. Members of the receptor tyrosine kinase family, which includes both FGFRs and VEGFRs, can be overexpressed in different kinds of tumor cells.
| Targets |
VEGFR1 (IC50 = 7 nM); VEGFR2 (IC50 = 25 nM); VEGFR3 (IC50 = 10 nM); FGFR1 (IC50 = 17.5 nM); FGFR2 (IC50 = 82.5 nM)
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| ln Vitro |
Lucitanib potently inhibits VEGF and bFGF-stimulated HUVEC proliferation with IC50 of 40 and 50 nM, respectively, which is consistent with the inhibitory activity of VEGFR and FGFR auto-phosphorylation. Also inhibiting CSF-1R with an IC50 of 5 nM is lucitanib (E-3810)[1]. The strongest inhibition of FGFR2 activity (Ki<0.05 μM) by lucentanib is observed for PDGFRα activity (Ki=0.11 μM). The range of values obtained for Ki is 0.26 to 8 μM for DDR2, LYN, CARDIAK, CSBP (2), EPHA2, and YES.
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| ln Vivo |
Oral lucitanib (E-3810) administered at a dose of 20 mg/kg for seven days in a row completely inhibits (P<0.01) the bFGF-induced angiogenic response in mice treated with vehicle. The xenografts tested (HT29 colon carcinoma, A2780 ovarian carcinoma, A498, SN12K1, and RXF393 renal carcinomas) all showed dose-dependent inhibition of tumor growth when lucitanib (E-3810) was applied. This indicates that the drug has diverse activity. When treatment is stopped, tumors resume growing, although E-3810 dramatically slows their growth during that time. In rare instances, tumor regression is also seen[1]. Tests are conducted on MDA-MB-231 breast cancer cells transplanted subcutaneously at a late stage, when tumor masses have reached 350–400 mg, to evaluate the efficacy of lucentanib (E-3810) at doses of 15 mg/kg. This tumor xenograft responds well to lucitanib (E-3810), and during the course of the 30-day treatment, the tumor completely stabilizes. Following the withdrawal of lucitanib (E-3810), tumors grow again at a pace comparable to control tumors, just like in other tumor models[3].
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| Cell Assay |
In complete medium, 96-well plates are seeded with exponentially growing HUVEC or NHI3T3 cells at a density of 3 to 6×103 cells/100 μL/well. In the experiments conducted without serum starvation, cells are seeded and exposed to varying concentrations of Lucitanib (E-3810) either with or without VEGF165 (50 ng/mL) or bFGF (20 ng/mL) ligands 24 hours later. The antiproliferative effect of the drugs is assessed using the MTS Colorimetric Assay after 72 hours. In the serum starvation assays, cells are cultured in medium containing 1% BSA three rounds of PBS washings after the entire medium is removed 24 hours after seeding. After processing, cells take 18 to 24 hours. A2780, A498, SN12KI, and HepG2 cells that are growing exponentially are seeded into 96-well plates at a density of 3 to 5×103 cells/100 μL/well in complete medium. After 24 hours, cells are exposed to various drug concentrations for 72 hours, and MTS is used to assess the antiproliferative effect[1].
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| Animal Protocol |
Mice: MDA-MB-231 tumor-bearing mice are randomized to receive SU 11248 (15 mg/kg), Brivanib, and Lucitanib (E-3810) at the doses used for the antitumor activity trial for ten days, once their tumor masses have reached approximately 350 to 400 mg. Tumor and plasma samples are taken in all groups (each with three animals) at one, four, and twenty-four hours following the intravenous injection of NSC 125973 at a dose of 20 mg/kg four hours following the antiangiogenic dose of day 7. The mice are put to sleep at the designated sampling time, blood is drawn into heparinized tubes from the retro-orbital plexus, and the plasma fraction is extracted. Tumors are removed and frozen, and cervical dislocation kills the mice. High-performance liquid chromatography (HPLC) with UV detection set at 230 nm is used to analyze the samples.
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| References |
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| Molecular Formula |
C26H25N3O4
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|---|---|
| Molecular Weight |
443.4944
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| Exact Mass |
443.18
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| Elemental Analysis |
C, 70.41; H, 5.68; N, 9.47; O, 14.43
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| CAS # |
1058137-23-7
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| Related CAS # |
1058137-23-7
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| Appearance |
Solid powder
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| SMILES |
CNC(=O)C1=CC=CC2=C1C=CC(=C2)OC3=C4C=C(C(=CC4=NC=C3)OCC5(CC5)N)OC
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| InChi Key |
CUDVHEFYRIWYQD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H25N3O4/c1-28-25(30)19-5-3-4-16-12-17(6-7-18(16)19)33-22-8-11-29-21-14-24(23(31-2)13-20(21)22)32-15-26(27)9-10-26/h3-8,11-14H,9-10,15,27H2,1-2H3,(H,28,30)
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| Chemical Name |
6-[7-[(1-aminocyclopropyl)methoxy]-6-methoxyquinolin-4-yl]oxy-N-methylnaphthalene-1-carboxamide
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| Synonyms |
E3810; AL3810; E-3810; AL 3810; E 3810; AL-3810
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~59 mg/mL (~122.9 mM)
Ethanol: ~30 mg/mL (~62.5 mM) Water: ~59 mg/mL (~122.9 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.64 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.64 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2548 mL | 11.2742 mL | 22.5484 mL | |
| 5 mM | 0.4510 mL | 2.2548 mL | 4.5097 mL | |
| 10 mM | 0.2255 mL | 1.1274 mL | 2.2548 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01283945 | Completed | Drug: Lucitanib | Solid Tumors | Institut de Recherches Internationales Servier |
July 2010 | Phase 1 Phase 2 |
| NCT02053636 | Completed | Drug: lucitanib | Breast Cancer | Institut de Recherches Internationales Servier |
December 2013 | Phase 2 |
| NCT03117101 | Completed | Drug: Lucitanib | Advanced Solid Tumors | Haihe Biopharma Co., Ltd. | March 2014 | Phase 1 |
| NCT01089543 | Completed | Drug: Rabeprazole Drug: Placebo |
Functional Dyspepsia | Eisai Co., Ltd. | April 2010 | Phase 2 |
| NCT01085695 | Completed | Drug: rabeprazole | Healthy | Eisai Co., Ltd. | April 2010 | Phase 1 |
 Characterization of immobilized E-3810.
Scatterplot of protein ratios obtained from theKdchemoproteomic assay.Mol Cell Proteomics.2014 Jun;13(6):1495-509. |
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 Identification of E-3810 targets via SILAC-based chemical proteomics competition assay. Mol Cell Proteomics.2014 Jun;13(6):1495-509. |
 Kdchemoproteomic assay with immobilized E-3810.Mol Cell Proteomics.2014 Jun;13(6):1495-509. |
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