Lenvatinib (E7080)

Catalog No.S1164

For research use only.

Lenvatinib (E7080) is a multi-target inhibitor, mostly for VEGFR2(KDR)/VEGFR3(Flt-4) with IC50 of 4 nM/5.2 nM, less potent against VEGFR1/Flt-1, ~10-fold more selective for VEGFR2/3 against FGFR1, PDGFRα/β in cell-free assays. Lenvatinib (E7080) also inhibits FGFR1-4, PDGFR, Kit (c-Kit), RET (c-RET), and shows potent antitumor activities. Phase 3.

Lenvatinib (E7080) Chemical Structure

CAS No. 417716-92-8

Selleck's Lenvatinib (E7080) has been cited by 57 publications

Purity & Quality Control

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Biological Activity

Description Lenvatinib (E7080) is a multi-target inhibitor, mostly for VEGFR2(KDR)/VEGFR3(Flt-4) with IC50 of 4 nM/5.2 nM, less potent against VEGFR1/Flt-1, ~10-fold more selective for VEGFR2/3 against FGFR1, PDGFRα/β in cell-free assays. Lenvatinib (E7080) also inhibits FGFR1-4, PDGFR, Kit (c-Kit), RET (c-RET), and shows potent antitumor activities. Phase 3.
Targets
RET [4]
()
VEGFR2/KDR [1]
(Cell-free assay)
VEGFR3/FLT4 [1]
(Cell-free assay)
VEGFR1/FLT1 [1]
(Cell-free assay)
PDGFRβ [1]
(Cell-free assay)
Click to View More Targets
4.0 nM 5.2 nM 22 nM 39 nM
In vitro

E7080, as a potent inhibitor of in vitro angiogenesis, shows a significantly inhibitory effect on VEGF/KDR and SCF/Kit signaling. According to the in vitro receptor tyrosine and serine/threonine kinase assays, E7080 inhibits Flt-1, KDR, Flt-4 with IC50 of 22, 4.0 and 5.2 nM, respectively. In addition to these kinases, E7080 also inhibits FGFR1 and PDGFR tyrosine kinases with IC50 value of 46, 51 and 100 nM for FGFR1, PDGFRα and PDGFRβ, respectively. [1] E7080 potently inhibits phosphorylation of VEGFR2 (IC50, 0.83 nM) and VEGFR3 (IC50, 0.36 nM) in HUVECs which is stimulated by VEGF and VEGF-C, respectively. [2] A recent study shows that E7080 treatment (both at 1 μM and 10 μM) results in a significant inhibition of cell migration and invasion by inhibiting FGFR and PDGFR signaling. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
TPC-1 and K1 cells NYnVO|JlTnWwY4Tpc44h[XO|YYm= Mn\NOVDjiIoQvF2= MYKyOEBp M1jPV3Rp\SCrbnjpZol1d3K7IHXm[oVkfHNib3[gcIVvfmG2aX7pZkBwdiC2aHWgeoli[mmuaYT5JI9nKGKxdHigZ4VtdCCuaX7ld{B4\XKnIH7veEBqdm[udXXuZ4VlKGK7IITo[UBt\XC2aX6geJJm[XSvZX70Mi=> NX\aXml{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{C5NFY{OjFpPkOwPVA3OzJzPD;hQi=>
ATC cells MknaSpVv[3Srb36gZZN{[Xl? NEXoOIMyNCB{NTDhcoQhPTBizszN NU[yPXZGPzJiaB?= NHu4flZRcG:|cHjvdplt[XSnZD;uc44ueGixc4Doc5J6dGG2ZXSgRYt1KG:{IFXST|EwOiCycn;0[YlveyBqZY\hcJVifGWmIHL5JGVNUVODKTDpckBt\W64YYTpcoljNXS{ZXH0[YQhe2GvcHzld{B4\XKnIIPp[45q\mmlYX70cJkhemWmdXPl[EBqdiCDVFOgZ4VtdCCldXz0eZJmey5? MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTVzN{GwN{c,Ojl3MUexNFM9N2F-
HCC cell lines Hep3B2.1-7, HuH-7, and JHH-7 MnzaVJJwdGmoZYLheIlwdiCjc4PhfS=> NGf1W5g3KGSjeYO= NHnS[YdN\W64YYTpcoljKHOqb4fl[EB{\WynY4TpeoUh[W6mIIDveIVvfCCjboTpdJJwdGmoZYLheIl3\SCjY4Tpeol1gSCjZ3HpcpN1KHSqZTDIR2Mh[2WubDDsbY5meyCKZYCzRlIvOeLCkEesJGh2UOLCkEesJIFv\CCMSFlihLA4NCC5aYToJGlEPTBidnHseYV{KG:oIECuNlMtKDBwNEKsJIFv\CByLk[0JO69dW:uL1ysJJJme3CnY4TpeoVtgS5? M3jhSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7N{OzOVEyLz5{OUezN|UyOTxxYU6=
HT29 cells MlzTR5l1d3SxeHnjbZR6KGG|c3H5 M{WyPFI2NCB3MDDuUS=> NGfsZlE4OiCq M2HFNIN6fG:2b4jpZ{Bld3OnOjC1NEBvVSCjbnSgco9v[3m2b4TvfIlkKGSxc3W6JFI2KG6P MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDhzNUS1Okc,OjR6MUW0OVY9N2F-
DX3 and U2OS cells NHXCPXhHfW6ldHnvckBie3OjeR?= NYP0fFlEOSEQvF2gZY5lKDFyIN88US=> MnfNNVYhcG:3coO= M4HHZ2xmdn[jdHnubYIhcW6qaXLpeEB1fW2xcjDj[YxteyCvaXfyZZRqd25iYX7kJIlvfmG|aX;uJIF1KGOxbnPlcpRz[XSrb37zJJRp[XRiYn;0bEBqdmirYnn0JIl1eyCtbn;3ckB1[XKpZYTzJIFv\CCjcnWgZYNpcWW4YXLs[UBkdGmwaXPhcIx6Ng>? NUXPeFlWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG3PFE{OTdpPkKxO|gyOzF5PD;hQi=>
Assay
Methods Test Index PMID
Western blot phospho-FGFR1 / FGFR1 /phospho-FRS2 / FRS2 / phospho-MEK / phospho-ERK ; phospho-RET ; Ki-67 / Cyclin D1 / CDK4 / p21 / p53 / Apaf-1 / p-NFκB / Bcl-2 / Cleaved-caspase 3 ; β-catenin ; Vimentin / E-cadherin / Snail / Zeb1 25295214 30286728
Growth inhibition assay Cell viability 25425971
In vivo

When orally administrated in a H146 xenograft model, E7080 inhibits the growth of H146 tumor at 30 and 100 mg/kg in a dose-dependent manner and leads to tumor regression at 100 mg/kg. Furthermore, E7080 at 100 mg/kg decreases microvessel density more than anti-VEGF antibody and imatinib treatment. [1] E7080 significantly inhibits local tumor growth in a MDA-MB-231 mammary fat pad (m.f.p.) model with RTVs (calculated tumor volume on day 8/tumor volume on day 1) of 0.81, and reduces both angiogenesis and lymphangiogenesis of established metastatic nodules of MDA-MB-231 tumor in the lymph nodes. [2]

Protocol (from reference)

Kinase Assay:

[1]

  • In vitro kinase assay [1]:

    Tyrosine kinase assays are performed by HTRF (KDR, VEGFR1, FGFR1, c-Met, EGFR) and ELISA (PDGFRβ), using the recombinant kinase domains of receptors. In both assays, 4 μL of serial dilutions of E7080 are mixed in a 96-well round plate with 10 μL of enzyme, 16 μL of poly (GT) solution (250 ng) and 10 μL of ATP solution (1 μM ATP) (final concentration of DMSO is 0.1%). In wells for blanks, no enzyme is added. In control wells no test article is added. The kinase reaction is initiated by adding ATP solution to each well. After 30-minute incubation at 30°C, the reaction is stopped by adding 0.5 M EDTA (10 μL/well) to the reaction mixture in each well. Dilution buffer adequate to each kinase assay is added to the reaction mixture. In the HTRF assay, 50 μL of the reaction mixture is transferred to a 96-well 1/2 area black EIA/RIA plate, HTRF solution (50 μL/well) is added to the reaction mixture, and then kinase activity is determined by measurement of fluorescence with a time-resolved fluorescence detector at an excitation wavelength of 337 nm and an emission wavelengths of 620 and 665 nm. In the ELISA, 50 μL of the reaction mixture is incubated in avidin coated 96-well polystyrene plates at room temperature for 30 minutes. After washing with wash buffer, PY20-HRP solution (70 μL/well) is added and the reaction mixture is incubated at room temperature for 30 minutes. After washing with wash buffer, TMB reagent (100 μL/well) is added to each well. After several minutes (10–30 minutes), 1 M H3PO4 (100 μL/well) is added to each well. Kinase activity is determined by measurement of absorbance at 450 nm with a microplate reader.

Cell Research:

[2]

  • Cell lines: HUVECs
  • Concentrations: 0-10 μM
  • Incubation Time: 72 hours
  • Method:

    HUVECs (1,000 cells in each well in serum-free medium containing 2% fetal bovine serum) and L6 rat skeletal muscle myoblasts (5,000 cells in each well in serum-free DMEM) are dispensed in a 96-well plate and incubated overnight. E7080 and either VEGF (20 ng/mL) or FGF-2 (20 ng/mL) containing 2% fetal bovine serum and PDGFβ (40 ng/mL) are added to each well. Cells are incubated for 3 days and then the ratios of surviving cells are measured by WST-1 reagent. For proliferation assay, samples are duplicated and three separate experiments are done.

  • (Only for Reference)
Animal Research:

[1]

  • Animal Models: H146 tumor cells are implanted subcutaneously (s.c.) into the flank region of female BALB/c nude mice.
  • Dosages: ≤100 mg/kg
  • Administration: Administered via p.o.
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 40 mg/mL
(93.7 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
0.5% methylcellulose
For best results, use promptly after mixing.

30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 426.85
Formula

C21H19ClN4O4

CAS No. 417716-92-8
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles COC1=CC2=NC=CC(=C2C=C1C(=O)N)OC3=CC(=C(C=C3)NC(=O)NC4CC4)Cl

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Calculation results:

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 ddH2O, 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.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04763408 Not yet recruiting Drug: Lenvatinib|Drug: Sorafenib Carcinoma Hepatocellular Eisai Inc. March 15 2021 --
NCT04287829 Recruiting Drug: Pembrolizumab|Drug: Lenvatinib Mesotheliomas Pleural The Netherlands Cancer Institute|Merck Sharp & Dohme Corp. March 1 2021 Phase 2
NCT04519151 Not yet recruiting Drug: Pembrolizumab|Drug: Lenvatinib Ovarian Neoplasms|Carcinoma Ovarian Epithelial|Neoplasm of Stomach|Ovarian Diseases|Genital Neoplasms Female|Ovarian Epithelial Tumor|Urogenital Neoplasms|Neoplasms Glandular and Epithelial Sheba Medical Center November 2020 Phase 2
NCT04522323 Recruiting Biological: MEDI5752|Drug: Axitinib|Drug: Lenvatinib Advanced Renal Cell Carcinoma MedImmune LLC August 5 2020 Phase 1

(data from https://clinicaltrials.gov, updated on 2021-09-06)

Tech Support

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