Home Protein Tyrosine Kinase VEGFR inhibitor - FGFR inhibitor - PDGFR inhibitor - c-Kit inhibitor - c-RET inhibitor Lenvatinib For research use only.

Lenvatinib

Synonyms: E7080

Lenvatinib 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 Chemical Structure

Lenvatinib Chemical Structure

CAS No. 417716-92-8

Purity & Quality Control

Lenvatinib Related Products

Signaling Pathway

VEGFR Signaling Pathways

VEGFR Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
TPC-1 and K1 cells Function assay 50 μM 24 h The inhibitory effects of lenvatinib on the viability of both cell lines were not influenced by the leptin treatment. 30906321
ATC cells Function assay 1, 25 and 50 μM 72 h Phosphorylated/non-phosphorylated Akt or ERK1/2 proteins (evaluated by ELISA) in lenvatinib-treated samples were significantly reduced in ATC cell cultures. 29517103
HCC cell lines Hep3B2.1-7, HuH-7, and JHH-7 Proliferation assay 6 days Lenvatinib showed selective and potent antiproliferative activity against the HCC cell lines Hep3B2.1‐7, HuH‐7, and JHH‐7, with IC50 values of 0.23, 0.42, and 0.64 μmol/L, respectively. 29733511
HT29 cells Cytotoxicity assay 25, 50 nM 72 h cytotoxic dose: 50 nM and noncytotoxic dose: 25 nM 24815456
DX3 and U2OS cells Function assay 1 μM and 10 μM 16 hours Lenvatinib inhibit tumor cells migration and invasion at concentrations that both inhibit its known targets and are achievable clinically. 21781317
Click to View More Cell Line Experimental Data

Biological Activity

Description Lenvatinib 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
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]
Kinase Assay 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 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.
Experimental Result Images Methods Biomarkers Images 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
Growth inhibition assay Cell viability 25425971
In Vivo
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]
Animal Research 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.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06161558 Not yet recruiting
Neoplasms
National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)
 May 15 2024 Phase 1
NCT05846724 Not yet recruiting
Kaposi Sarcoma|Classic Kaposi Sarcoma|Refractory Kaposi Sarcoma
Fondazione IRCCS Ca'' Granda Ospedale Maggiore Policlinico
 February 1 2024 Phase 2
NCT05903833 Not yet recruiting
Recurrent Vulvar Cancer|Persistent Vulvar Cancer|Metastatic Vulva Cancer|Locally Advanced Vulvar Cancer
AGO Research GmbH
 January 1 2024 Phase 2
NCT05901194 Not yet recruiting
Hepatocellular Carcinoma Non-resectable
Assistance Publique - Hôpitaux de Paris|Laboratoire EISAI
 June 2023 Phase 1|Phase 2

Chemical Information & Solubility

Molecular Weight 426.85 Formula

C21H19ClN4O4
CAS No. 417716-92-8 SDF Download Lenvatinib SDF
Smiles COC1=CC2=NC=CC(=C2C=C1C(=O)N)OC3=CC(=C(C=C3)NC(=O)NC4CC4)Cl
Storage (From the date of receipt)

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DMSO : 20 mg/mL ( (46.85 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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