1. Protein Tyrosine Kinase/RTK
  2. VEGFR
    FGFR

E-3810 (Synonyms: Lucitanib)

Cat. No.: HY-15391 Purity: 98.24%
Handling Instructions

E-3810 is a novel dual inhibitor of VEGFR and FGFR, potently and selectively inhibits VEGFR1, VEGFR2, VEGFR3, FGFR1 and FGFR2 with IC50s of 7 nM, 25 nM, 10 nM, 17.5 nM, and 82.5 nM, respectively.

For research use only. We do not sell to patients.

E-3810 Chemical Structure

E-3810 Chemical Structure

CAS No. : 1058137-23-7

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 222 In-stock
Estimated Time of Arrival: December 31
2 mg USD 132 In-stock
Estimated Time of Arrival: December 31
5 mg USD 228 In-stock
Estimated Time of Arrival: December 31
10 mg USD 372 In-stock
Estimated Time of Arrival: December 31
50 mg USD 1056 In-stock
Estimated Time of Arrival: December 31
100 mg   Get quote  
200 mg   Get quote  

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    E-3810 purchased from MCE. Usage Cited in: Science. 2017 Dec 1;358(6367). pii: eaan4368.

    Kinobead western Blot readout for selected inhibitor:protein combinations.

    E-3810 purchased from MCE. Usage Cited in: Science. 2017 Dec 1;358(6367). pii: eaan4368.

    Immunoblot analysis in MV-4-11 cells and MOLM-13, FLT3-WT and FLT3-ITD transfected HEK293 cells, and Ba/F3 FLT3-ITD cells revealed FLT3 target engagement for Golvatinib and Cabozantinib.

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    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    E-3810 is a novel dual inhibitor of VEGFR and FGFR, potently and selectively inhibits VEGFR1, VEGFR2, VEGFR3, FGFR1 and FGFR2 with IC50s of 7 nM, 25 nM, 10 nM, 17.5 nM, and 82.5 nM, respectively.

    IC50 & Target[1]

    VEGFR1

    7 nM (IC50)

    VEGFR2

    25 nM (IC50)

    VEGFR3

    10 nM (IC50)

    FGFR1

    17.5 nM (IC50)

    FGFR2

    82.5 nM (IC50)

    In Vitro

    Consistent with the inhibitory activity of VEGFR and FGFR auto-phosphorylation, E-3810 potently inhibits VEGF and bFGF-stimulated HUVEC proliferation with IC50 of 40 and 50 nM, respectively. Besides, E-3810 also inhibits CSF-1R with IC50 of 5 nM[1]. E-3810 potently inhibits FGFR2 activity (Ki<0.05 μM), follows by PDGFRα activity (Ki=0.11 μM). The Ki values obtained for DDR2, LYN, CARDIAK, CSBP (2), EPHA2, and YES range between 0.26 and 8 μM[2].

    In Vivo

    E-3810, at oral dosing of 20 mg/kg for 7 consecutive days, completely inhibits (P<0.01) the bFGF induced angiogenic response compare with the response in vehicle-treated mice. E-3810 shows a broad spectrum of activity, being active in all the xenografts tested (HT29 colon carcinoma, A2780 ovarian carcinoma, A498, SN12K1, and RXF393 renal carcinomas) with dose-dependent inhibition of tumor growth. E-3810 significantly delays growth during treatment, but tumors resume their growth when treatment is suspended; in a few cases, tumor regression is observed[1]. The activity of E-3810 given at the doses of 15 mg/kg is tested on MDA-MB-231 breast cancer transplanted subcutaneously, at a late stage, when tumor masses reach 350 to 400 mg. This tumor xenograft is very sensitive to E-3810, with complete tumor stabilization lasting throughout the 30-day treatment. As in other tumor models, tumors re-grow after withdrawal of E-3810 at a rate similar to control tumors[3].

    Clinical Trial
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 25 mg/mL (56.37 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 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
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 2.5 mg/mL (5.64 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.5 mg/mL (5.64 mM); Clear solution

    • 3.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: ≥ 2.5 mg/mL (5.64 mM); Clear solution

    References
    Kinase Assay
    [2]

    Kinase selectivity is measured using the “Kinase Profiler” service, based on a radiometric filter-binding assay. Briefly, five different concentrations of E-3810 (0.1 μM, 0.3 μM, 1 μM, 3 μM, and 10 μM) are tested using an ATP concentration corresponding to the Michaelis-Menten constant (Km) of each selected kinase, as under the condition [ATP]=Km, the general formula to compute the dissociation constant for the inhibitor (Ki)—that is, Ki=IC50×Km/([ATP]+Km)—can be simplified to Ki=IC50/2. Therefore, in our assay the measured IC50 is directly proportional to Ki. Kinase inhibition is expressed as the percentage of activity determined in the absence of inhibitor versus in the presence of inhibitor. Sigmoid concentration-response curves plotting percentages of effect versus the log concentration of E-3810 are analyzed using nonlinear regression analysis using GraphPad Prism to obtain IC50 values, and Ki values are computed using the formula mentioned above[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [1]

    Exponentially growing HUVEC or NHI3T3 cells are seeded into 96-well plates at a density of 3 to 6×103 cells/100 μL/well in complete medium. In the experiments without serum starvation, 24 hours after seeding, cells are exposed to different E-3810 concentrations without or with VEGF165 (50 ng/mL) or bFGF (20 ng/mL) ligands and the antiproliferative effect of the drugs is evaluated after 72 hours by MTS Colorimetric Assay. In the assays with serum starvation conditions, 24 hours after seeding complete medium is removed and after 3 rounds of washing with PBS, cells are cultured in medium containing 1% BSA. After 18 to 24 hours, cells are processed. Exponentially growing A2780, A498, SN12KI, and HepG2 cells are seeded into 96-well plates at 3 to 5×103 cells/100 μL/well in complete medium. Twenty-four hours later cells are treated with different drug concentrations for 72 hours and the antiproliferative effect is evaluated by MTS[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2]

    Mice[3]
    MDA-MB-231 tumor-bearing mice are randomized when their tumor masses are about 350 to 400 mg to receive E-3810 (15 mg/kg), Brivanib, and Sunitinib at the doses used for the antitumor activity trial, for 10 days. Four hours after the antiangiogenic dose of day 7, Paclitaxel is injected intravenously at the dose of 20 mg/kg and tumor and plasma samples are collected after 1, 4, and 24 hours in all the groups (each group consisting of 3 animals). At the indicated sampling time, mice are anesthetized, blood is collected from the retro-orbital plexus into heparinized tubes, and the plasma fraction is separated. Mice are killed by cervical dislocation, and tumors excised and snap-frozen. The samples are analyzed by high-performance liquid chromatography (HPLC) with UV detection at 230 nm.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    443.49

    Formula

    C₂₆H₂₅N₃O₄

    CAS No.

    1058137-23-7

    SMILES

    O=C(NC)C1=CC=CC2=C1C=CC(OC3=CC=NC4=CC(OCC5(N)CC5)=C(OC)C=C43)=C2

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 98.24%

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