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2mg |
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5mg |
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50mg |
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100mg |
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250mg |
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500mg |
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1g |
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Other Sizes |
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Purity: ≥98%
Lenvatinib (formerly E-7080, ER-203492-00; trade name Lenvima among others) is a potent and orally bioavailable multi-targeted kinase [VEGFR2(KDR)/VEGFR3(Flt-4)] inhibitor with potential antitumor activity. With IC50 values of 4 nM and 5.2 nM, respectively, it inhibits VEGFR2/VEGFR3, and in cell-free assays, it has less potency against VEGFR1/Flt-1. In 2015, lenitinib was licensed for the treatment of differentiated thyroid cancer that was not responsive to radioactive iodine (radioiodine) treatment and was either locally recurrent or metastatic.
Targets |
VEGFR1 (IC50 = 22 nM); VEGFR2 (IC50 = 4 nM); VEGFR3 (IC50 = 5.2 nM); FGFR1 (IC50 = 46 nM); PDGFRα (IC50 = 51 nM); PDGFRβ (IC50 = 39 nM); c-Kit (IC50 = 100 nM); FGFR2; FGFR3; FGFR4; RET
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ln Vitro |
Lenvatinib (E7080) has IC50s of 4, 5.2, and 22 nM for VEGFR1 (Flt-1), VEGFR3 (Flt-4), and VEGFR2 (KDR), in that order. FGFR1, PDGFRβ, KIT, and TCGF are all inhibited by lentinib, with IC50 values of 51, 39, 46, and 100 nM, respectively[3].
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ln Vivo |
Lenvatinib (E7080) (100 mg/kg, p.o.) also significantly inhibits metastasis to both distant lung and regional lymph nodes after treatment concludes, in addition to significantly inhibiting local tumor growth at the m.f.p.[3].
Lenvatinib (E7080) causes tumor regression in the H146 xenograft model at 100 mg/kg and dose-dependently suppresses the growth of the H146 tumor at 30 and 100 mg/kg (BID, QDx21). Lenvatinib at 100 mg/kg reduces microvessel density more than anti-VEGF antibody and STI571 treatment, according to IHC analysis using anti-CD31 antibody[4].
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Enzyme Assay |
Recombinant kinase domains of receptors are used in HTRF (KDR, VEGFR1, FGFR1, c-Met, EGFR) and ELISA (PDGFRβ) tyrosine kinase assays. In both assays, 10 μL of enzyme, 16 μL of poly (GT) solution (250 ng), and 10 μL of ATP solution (1 μM ATP) are combined with 4 μL of serial dilutions of E7080 in a 96-well round plate (final concentration of DMSO is 0.1%). Enzyme is not added to blank wells. There is no test article added to control wells. Each well receives an addition of ATP solution to start the kinase reaction. The reaction is terminated by adding 0.5 M EDTA (10 μL/well) to the reaction mixture in each well following a 30-minute incubation period at 30°C. The reaction mixture is supplemented with dilution buffer appropriate for each kinase assay. The HTRF assay involves transferring 50 μL of the reaction mixture to a 96-well 1/2 area black EIA/RIA plate, adding 50 μL of HTRF solution per well, and measuring the fluorescence of the reaction mixture using a time-resolved fluorescence detector at 620 and 665 nm for emission and 337 nm for excitation. This allows for the determination of kinase activity. For the ELISA, 96-well polystyrene plates coated with avidin are incubated at room temperature for 30 minutes with 50 μL of the reaction mixture. Following washing with wash buffer, the reaction mixture is incubated at room temperature for 30 minutes before PY20-HRP solution (70 μL/well) is added. In each well, 100 μL of TMB reagent is added following washing with wash buffer. Each well receives 100 μL of 1 M H3PO4 after a few minutes (10–30 minutes). By measuring absorbance at 450 nm with a microplate reader, kinase activity can be identified.
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Cell Assay |
H146 (1.2×103 cells/50 μL/well) are cultured in 96-well multi-plates with SFM containing 0.5% BSA. Following an overnight culture at 37°C, SFM (150 μL/well) containing 0.5% FBS and various SCF concentrations are added, either with or without various compound concentrations. WST-1 is used to measure the ratios of surviving cells following a 72-hour culture.
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Animal Protocol |
Clean-room conditions are used to maintain 8–12 week old, 20–25 g female BALB/c nude mice. Mice's flanks are subcutaneously (s.c.) implanted with 6.5×106 H146 tumor cells. Day 1 of the experiment occurs twelve days after the injection when mice are randomized into treatment (n = 6 or n = 5) and control (n = 12) groups. From day one to day twenty-one, lenvatinib, STI571, and VEGF neutralization antibody are given orally twice daily for lenvatinib and STI571 and twice weekly for the antibody. These substances are suspended in 0.5% methylcellulose and saline, respectively. On the designated days, tumor volume is measured and computed. Relative tumor volume (RTV) is a measure of antitumor activity that is calculated as the volume of the tumor on day 1 divided by the tumor volume at indicated days.
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References |
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Molecular Formula |
C21H19CLN4O4
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Molecular Weight |
426.85
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Exact Mass |
426.11
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Elemental Analysis |
C, 59.09; H, 4.49; Cl, 8.30; N, 13.13; O, 14.99
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CAS # |
417716-92-8
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Appearance |
Solid powder
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SMILES |
COC1=CC2=NC=CC(=C2C=C1C(=O)N)OC3=CC(=C(C=C3)NC(=O)NC4CC4)Cl
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InChi Key |
WOSKHXYHFSIKNG-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C21H19ClN4O4/c1-29-19-10-17-13(9-14(19)20(23)27)18(6-7-24-17)30-12-4-5-16(15(22)8-12)26-21(28)25-11-2-3-11/h4-11H,2-3H2,1H3,(H2,23,27)(H2,25,26,28)
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Chemical Name |
4-[3-chloro-4-(cyclopropylcarbamoylamino)phenoxy]-7-methoxyquinoline-6-carboxamide
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Synonyms |
E-7080; E7080; E 7080; ER-203492-00; Lenvatinib; Brand name: Lenvima
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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) |
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Solubility (In Vivo) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.3427 mL | 11.7137 mL | 23.4274 mL | |
5 mM | 0.4685 mL | 2.3427 mL | 4.6855 mL | |
10 mM | 0.2343 mL | 1.1714 mL | 2.3427 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 |
NCT04447755 | Active Recruiting |
Drug: Lenvatinib | Relapsed or Refractory Solid Tumors |
Merck Sharp & Dohme LLC | July 30, 2020 | Phase 2 |
NCT04622566 | Not yet recruiting | Drug: Lenvatinib, Pembrolizumab | Mucosal Melanoma Neoadjuvant Treatment |
Peking University Cancer Hospital & Institute |
December 30, 2020 | Phase 2 |
NCT04297254 | Recruiting | Drug: Imatinib Mesylate | Carcinoma, Hepatocellular | Eisai Pharmaceuticals India Pvt. Ltd |
February 4, 2021 | Phase 4 |
NCT05308901 | Recruiting | Drug: Lenvatinib Drug: Pembrolizumab |
Melanoma, Uveal | Providence Health & Services | August 2, 2022 | Phase 2 |
NCT04519151 | Recruiting | Drug: Lenvatinib Drug: Pembrolizumab |
Ovarian Neoplasms Ovarian Diseases |
Sheba Medical Center | April 12, 2021 | Phase 2 |
Kinase inhibitory profile of E7080. Int J Cancer . 2008 Feb 1;122(3):664-71. td> |
Effect of E7080 on SCF- and VEGF-induced angiogenesis in the sandwich tube formation (sTF) assay. Int J Cancer . 2008 Feb 1;122(3):664-71. td> |
Comparison of effects of E7080 and imatinib on SCF- and VEGF-induced angiogenesis in the sandwich tube formation (sTF) assay. Int J Cancer . 2008 Feb 1;122(3):664-71. td> |
Effects of lenvatinib for ATC. Cancer Control . 2018 Jan-Dec;25(1):1073274818789361. td> |