E-3810

VEGF/FGF dual inhibitor, potent and selective CAS# 1058137-23-7

E-3810

Catalog No. BCC1541----Order now to get a substantial discount!

Product Name & Size Price Stock
E-3810: 5mg $230 In Stock
E-3810: 10mg Please Inquire In Stock
E-3810: 20mg Please Inquire Please Inquire
E-3810: 50mg Please Inquire Please Inquire
E-3810: 100mg Please Inquire Please Inquire
E-3810: 200mg Please Inquire Please Inquire
E-3810: 500mg Please Inquire Please Inquire
E-3810: 1000mg Please Inquire Please Inquire
Related Products

Quality Control of E-3810

Number of papers citing our products

Chemical structure

E-3810

3D structure

Chemical Properties of E-3810

Cas No. 1058137-23-7 SDF Download SDF
PubChem ID 25031915 Appearance Powder
Formula C26H25N3O4 M.Wt 443.49
Type of Compound N/A Storage Desiccate at -20°C
Synonyms Lucitanib
Solubility DMSO : ≥ 25 mg/mL (56.37 mM)
*"≥" means soluble, but saturation unknown.
Chemical Name 6-[7-[(1-aminocyclopropyl)methoxy]-6-methoxyquinolin-4-yl]oxy-N-methylnaphthalene-1-carboxamide
SMILES CNC(=O)C1=CC=CC2=C1C=CC(=C2)OC3=C4C=C(C(=CC4=NC=C3)OCC5(CC5)N)OC
Standard InChIKey CUDVHEFYRIWYQD-UHFFFAOYSA-N
Standard InChI InChI=1S/C26H25N3O4/c1-28-25(30)19-5-3-4-16-12-17(6-7-18(16)19)33-22-8-11-29-21-14-24(23(31-2)13-20(21)22)32-15-26(27)9-10-26/h3-8,11-14H,9-10,15,27H2,1-2H3,(H,28,30)
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of E-3810

DescriptionE-3810 is a potent and selective dual inhibitor of VEGF and FGF receptors with IC50 values of 7 nM, 25 nM, 10 nM, 17.5 nM and 82.5 nM for VEGFR-1, VEGFR-2, VEGFR-3, FGFR-1 and FGFR-2, respectively.
TargetsVEGFR-1VEGFR-2VEGFR-3FGFR-1FGFR-2  
IC507 nM25 nM10 nM17.5 nM82.5 nM  

Protocol

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].

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].

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.

References:
[1]. Bello E, et al. E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405. [2]. Colzani M, et al. Quantitative chemical proteomics identifies novel targets of the anti-cancer multi-kinase inhibitor E-3810. Mol Cell Proteomics. 2014 Jun;13(6):1495-509. [3]. Bello E, et al. The tyrosine kinase inhibitor E-3810 combined with paclitaxel inhibits the growth of advanced-stage triple-negative breast cancer xenografts. Mol Cancer Ther. 2013 Feb;12(2):131-40.

E-3810 Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

E-3810 Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of E-3810

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 2.2548 mL 11.2742 mL 22.5484 mL 45.0968 mL 56.3711 mL
5 mM 0.451 mL 2.2548 mL 4.5097 mL 9.0194 mL 11.2742 mL
10 mM 0.2255 mL 1.1274 mL 2.2548 mL 4.5097 mL 5.6371 mL
50 mM 0.0451 mL 0.2255 mL 0.451 mL 0.9019 mL 1.1274 mL
100 mM 0.0225 mL 0.1127 mL 0.2255 mL 0.451 mL 0.5637 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on E-3810

E-3810 is a small-molecule dual inhibitor of VEGF and FGF receptors with IC 50 values of 7, 25, 10, 17.5, 82.5 and 237.5 nM for VEGFR-1, 2, 3, FGFR-1, 2 and 3, respectively [1].
The vascular endothelial growthfactor (VEGF) and fibroblast growth factor (FGF) are important factors in angiogenesis. They promote the process of angiogenesis through binding to their associated tyrosine kinase receptors and trigger a cascade signaling pathway that finally leads to the increased proliferation of the blood vessel cells and permeability of the vessels. Tumor cells are rapidly proliferating cells which need more vessels to deliver nutrients, therefore VEGFR and FGFR are attractive targets in antitumor treatment. As a selective inhibitor of VEGFR and FGFR, E-3810 shows potent effects in both in vitro and in vivo assays [1].
E-3810 exerted potent inhibition effects on all the three receptors of VEGFR family and two members (FGFR-1 and 2) of FGFR family in MTS assay. It also had effects on colony stimulating factor (CSF)-1R with IC50 value of 5 nM. When treated with human umbelical vein cells (HUVEC), E-3810 significantly inhibited cell proliferation induced by the addition of VEGF and bFGF with IC50 values of 40 and 50 nM, respectively. In NIH3T3 cells, E-3810 showed no inhibitory efficacy on PDGFR until the concentration of it was up to μM range, demonstrating the selectivity of E-3810 [1].
In the mice model, oral administration of 20 mg/kg E-3810 for 7 days significantly inhibited vessel formation induced by bFGF. E-3810 also exerted effective inhibition on tumor growth in variety of human tumor xenografts such as A498, HT29 and A2780. Besides that, it was reported that the combination treatment of E-3810 and paclitaxel showed higher antitumor activity than that of paclitaxel with brivanib or sunitinib in the MDA-MB-231 breast cancer xenografts [1, 2].
References:
[1]. Bello E, Colella G, Scarlato V, et al. E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer research, 2011, 71(4): 1396-1405.
[2]. Bello E, Taraboletti G, Colella G, et al. The tyrosine kinase inhibitor E-3810 combined with paclitaxel inhibits the growth of advanced-stage triple-negative breast cancer xenografts. Molecular cancer therapeutics, 2013, 12(2): 131-140.

Featured Products
New Products
 

References on E-3810

HPLC-MS/MS method for quantitative determination of the novel dual inhibitor of FGF and VEGF receptors E-3810 in tumor tissues from xenograft mice and human biopsies.[Pubmed:24446259]

J Mass Spectrom. 2014 Jan;49(1):19-26.

We developed and validated a high-performance liquid chromatography-tandem mass spectrometry analytical method to measure E-3810, a novel dual inhibitor of fibroblast growth factor receptor 1 and vascular endothelial growth factor receptor 1-3 in tissues and determined the drug concentration in a biopsy of human breast cancer for the first time. The method is a modification of our previous one in plasma to study the clinical pharmacokinetics of the drug during the phase I/II trial. In view of the changes in matrix, we applied a partial validation protocol to determine recovery, sensitivity, range of linearity, precision, accuracy and stability of the method over three runs in a mouse tumor tissue and liver. The recovery of E-3810 from liver or tumor homogenate was >69%, and the lower limit of quantification was 5 ng/ml. The method was linear in the concentration range 5.0-500.0 ng/ml, as demonstrated by a determination coefficient R(2) >/= 0.9955. The range of the calibration curve was appropriate for the analysis, as demonstrated by the accuracy, which was between 91.4% and 106.7%. Interday precision and accuracy on quality control samples at 9, 30 and 300 ng/ml were 3.1-11.2% and 98.3-111.4%, respectively. The assay was applied successfully to determine the intratumor concentration of E-3810 in different mouse xenograft tumor models and in a biopsy of a patient with breast cancer included in the phase I/II trial of the drug. In mouse tumors, the concentrations of E-3810 were higher than necessary to exert antitumor activity in vitro (1 microM). Even more of interest was the result obtained in a human biopsy of few milligrams, where E-3810 reached 4.9 microg/g (11 microM).

Quantitative chemical proteomics identifies novel targets of the anti-cancer multi-kinase inhibitor E-3810.[Pubmed:24696502]

Mol Cell Proteomics. 2014 Jun;13(6):1495-509.

Novel drugs are designed against specific molecular targets, but almost unavoidably they bind non-targets, which can cause additional biological effects that may result in increased activity or, more frequently, undesired toxicity. Chemical proteomics is an ideal approach for the systematic identification of drug targets and off-targets, allowing unbiased screening of candidate interactors in their natural context (tissue or cell extracts). E-3810 is a novel multi-kinase inhibitor currently in clinical trials for its anti-angiogenic and anti-tumor activity. In biochemical assays, E-3810 targets primarily vascular endothelial growth factor and fibroblast growth factor receptors. Interestingly, E-3810 appears to inhibit the growth of tumor cells with low to undetectable levels of these proteins in vitro, suggesting that additional relevant targets exist. We applied chemical proteomics to screen for E-3810 targets by immobilizing the drug on a resin and exploiting stable isotope labeling by amino acids in cell culture to design experiments that allowed the detection of novel interactors and the quantification of their dissociation constant (Kd imm) for the immobilized drug. In addition to the known target FGFR2 and PDGFRalpha, which has been described as a secondary E-3810 target based on in vitro assays, we identified six novel candidate kinase targets (DDR2, YES, LYN, CARDIAK, EPHA2, and CSBP). These kinases were validated in a biochemical assay and-in the case of the cell-surface receptor DDR2, for which activating mutations have been recently discovered in lung cancer-cellular assays. Taken together, the success of our strategy-which integrates large-scale target identification and quality-controlled target affinity measurements using quantitative mass spectrometry-in identifying novel E-3810 targets further supports the use of chemical proteomics to dissect the mechanism of action of novel drugs.

The tyrosine kinase inhibitor E-3810 combined with paclitaxel inhibits the growth of advanced-stage triple-negative breast cancer xenografts.[Pubmed:23270924]

Mol Cancer Ther. 2013 Feb;12(2):131-40.

E-3810 is a novel small molecule that inhibits VEGF receptor-1, -2, and -3 and fibroblast growth factor receptor-1 tyrosine kinases at nmol/L concentrations currently in phase clinical II. In preclinical studies, it had a broad spectrum of antitumor activity when used as monotherapy in a variety of human xenografts. We here investigated the activity of E-3810 combined with different cytotoxic agents in a MDA-MB-231 triple-negative breast cancer xenograft model. The molecule could be safely administered with 5-fluorouracil, cisplatin, and paclitaxel. The E-3810-paclitaxel combination showed a striking activity with complete, lasting tumor regressions; the antitumor activity of the combination was also confirmed in another triple-negative breast xenograft, MX-1. The activity was superior to that of the combinations paclitaxel+brivanib and paclitaxel+sunitinib. Pharmacokinetics studies suggest that the extra antitumor activity of the combination is not due to higher paclitaxel tumor levels, which in fact were lower in mice pretreated with all three kinase inhibitors, and the paclitaxel plasma levels excluded reduced drug availability. Pharmacodynamic studies showed that E-3810, brivanib, and sunitinib given as single agents or in combination with paclitaxel reduced the number of vessels, but did not modify vessel maturation. Reduced tumor collagen IV and increased plasma collagen IV, associated with increased matrix metalloproteinases (MMP), particularly host MMP-9, indicate a proteolytic remodeling of the extracellular matrix caused by E-3810 that in conjunction with the cytotoxic effect of paclitaxel on the tumor cells (caspase-3/7 activity) may contribute to the striking activity of their combination. These data support the therapeutic potential of combining E-3810 with conventional chemotherapy.

Description

Lucitanib (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.

Keywords:

E-3810,1058137-23-7,Lucitanib,Natural Products,FGFR, buy E-3810 , E-3810 supplier , purchase E-3810 , E-3810 cost , E-3810 manufacturer , order E-3810 , high purity E-3810

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: