Lenvatinib (E7080)

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. Phase 3.

Price Stock Quantity  
In DMSO USD 300 In stock
USD 70 In stock
USD 150 In stock
USD 270 In stock
USD 770 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

Lenvatinib (E7080) Chemical Structure

Lenvatinib (E7080) Chemical Structure
Molecular Weight: 426.85

Validation & Quality Control

Customer Reviews(2)

Quality Control & MSDS

Related Compound Libraries

VEGFR Inhibitors with Unique Features

Product Information

  • Compare VEGFR Inhibitors
    Compare VEGFR Products
  • Research Area

Product Description

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. Phase 3.
Targets VEGFR2/KDR [1] VEGFR3/FLT4 [1] VEGFR1/FLT1 [1] PDGFRβ [1] FGFR1 [1]

   View More

IC50 4.0 nM 5.2 nM 22 nM 39 nM 46 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]
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]
Features

Protocol(Only for 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 Assay: [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.

Animal Study: [1]

Animal Models H146 tumor cells are implanted subcutaneously (s.c.) into the flank region of female BALB/c nude mice.
Formulation E7080 is dissolved in suspended in 0.5% methylcellulose.
Dosages ≤100 mg/kg
Administration Administered via p.o.
Solubility 0.5% methylcellulose, , 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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Matsui J, et al. Int J Cancer. 2008, 122(3), 664-671.

[2] Matsui J, et al. Clin Cancer Res. 2008, 14(17),5459-5465.

view more

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2014-08-23)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT01877083 Recruiting KIF5B-RET-Positive Adenocarcinoma of the Lung Eisai Inc.|Eisai Co., Ltd. April 2013 Phase 2
NCT01761266 Recruiting Hepatocellular Carcinoma (HCC) Eisai Inc.|Eisai Limited February 2013 Phase 3
NCT01133977 Active, not recruiting Stage IV Melanoma Eisai Inc.|Quintiles December 2012 Phase 1|Phase 2
NCT01728623 Recruiting Thyroid Cancer Eisai Inc.|Eisai Co., Ltd. August 2012 Phase 2
NCT02199392 Completed P-glycoprotein|Healthy Volunteers Eisai Inc. November 2011 Phase 1

view more

Chemical Information

Download Lenvatinib (E7080) SDF
Molecular Weight (MW) 426.85
Formula

C21H19ClN4O4

CAS No. 417716-92-8
Storage 3 years -20℃Powder
6 months-80℃in DMSO
Synonyms
Solubility (25°C) * In vitro DMSO 40 mg/mL (93 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 0.5% methylcellulose, 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* 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 Name 1-(4-(6-carbamoyl-7-methoxyquinolin-4-yloxy)-2-chlorophenyl)-3-cyclopropylurea

Research Area

Customer Reviews (2)


Click to enlarge
Rating
Source Chin J Cancer Res. 2013 Oct;25(5):572-84 . Lenvatinib (E7080) purchased from Selleck
Method RTCA
Cell Lines HT29 cells
Concentrations 6.25-100 nM
Incubation Time 12, 24, 36 h
Results E7080 treated HT29 cells exhibited decreasing CI values in a concentration-dependent manner. While 100 nmol/L has shown complete cytotoxic effect and decreased CI to 0.1, 50 nmol/L decreased CI to 0.4. Both showed statistically significant cytotoxic effect when compared with the control (P<0.05).

Click to enlarge
Rating
Source Chin J Cancer Res. 2013 Oct;25(5):572-84 . Lenvatinib (E7080) purchased from Selleck
Method RTCA
Cell Lines HT29 cells
Concentrations
Incubation Time 24 h
Results Twenty-four hours after treatment with E7080, the IC50 of 5.60×10-8 mol/L was achieved. Calculation of IC50 of E7080 (IC50 =5.60×10–8 mol/L, square R =0.998).

Product Citations (3)

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related VEGFR Products

  • SKLB1002

    SKLB1002 is a potent and ATP-competitive VEGFR2 inhibitor with IC50 of 32 nM.

  • CO-1686 (AVL-301)

    CO-1686 is an irreversible, mutant-selective EGFR inhibitor with Ki of 21.5 nM and 303.3 nM for EGFRL858R/T790M and EGFRWT, respectively. Phase 2.

  • AZD9291

    AZD9291 is an oral, irreversible, and mutant-selective EGFR inhibitor with IC50 of 12.92, 11.44 and 493.8 nM for Exon 19 deletion EGFR, L858R/T790M EGFR, and WT EGFR, respectively. Phase 3.

  • Cabozantinib (XL184, BMS-907351)

    Cabozantinib (XL184, BMS-907351) is a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM, respectively.

  • Nintedanib (BIBF 1120)

    Nintedanib (BIBF 1120) is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM. Phase 3.

  • Regorafenib (BAY 73-4506)

    Regorafenib (BAY 73-4506) is a multi-target inhibitor for VEGFR1, VEGFR2, VEGFR3, PDGFRβ, Kit, RET and Raf-1 with IC50 of 13 nM/4.2 nM/46 nM, 22 nM, 7 nM, 1.5 nM and 2.5 nM, respectively.

  • Axitinib

    Axitinib is a multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ and c-Kit with IC50 of 0.1 nM, 0.2 nM, 0.1-0.3 nM, 1.6 nM and 1.7 nM, respectively.

    Features:Superior as second-line therapy relative to sorafenib (current standard-of-care).

  • Vandetanib (ZD6474)

    Vandetanib (ZD6474) is a potent inhibitor of VEGFR2 with IC50 of 40 nM.

  • Pazopanib HCl (GW786034 HCl)

    Pazopanib (GW786034) is a novel multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFR, FGFR, c-Kit and c-Fms with IC50 of 10 nM, 30 nM, 47 nM, 84 nM, 74 nM, 140 nM and 146 nM, respectively.

    Features:A multi-kinase inhibitor.

  • Cediranib (AZD2171)

    Cediranib (AZD2171) is a highly potent VEGFR(KDR) inhibitor with IC50 of <1 nM, also inhibits Flt1/4 with IC50 of 5 nM/≤3 nM, similar activity against c-Kit and PDGFRβ, 36-, 110-fold and >1000-fold selective more for VEGFR than PDGFR-α, CSF-1R and Flt3, Phase 3.

Recently Viewed Items

Tags: buy Lenvatinib (E7080) | Lenvatinib (E7080) supplier | purchase Lenvatinib (E7080) | Lenvatinib (E7080) cost | Lenvatinib (E7080) manufacturer | order Lenvatinib (E7080) | Lenvatinib (E7080) distributor
Contact Us