Home Protein Tyrosine Kinase c-Met inhibitor - VEGFR inhibitor Golvatinib (E7050) For research use only.

Golvatinib (E7050)

Golvatinib (E7050) is a dual c-Met and VEGFR-2 inhibitor with IC50 of 14 nM and 16 nM, does not inhibit bFGF-stimulated HUVEC growth (up to 1000 nM). Phase 1/2.

Golvatinib (E7050) Chemical Structure

Golvatinib (E7050) Chemical Structure

CAS No. 928037-13-2

Purity & Quality Control

Batch: S285901 DMSO]20 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 99.78%
99.78

Golvatinib (E7050) Related Products

Signaling Pathway

c-Met Signaling Pathways

c-Met Signaling Pathway

Biological Activity

Description Golvatinib (E7050) is a dual c-Met and VEGFR-2 inhibitor with IC50 of 14 nM and 16 nM, does not inhibit bFGF-stimulated HUVEC growth (up to 1000 nM). Phase 1/2.
Targets
c-Met [1] VEGFR2 [1]
14 nM 16 nM
In vitro
In vitro In vitro studies indicate that E7050 potently inhibits phosphorylation of both c-Met and VEGFR-2. E7050 also potently represses the growth of both c-met amplified tumor cells and endothelial cells stimulated with either HGF or VEGF. [1] E7050 circumvents resistance to all of the reversible, irreversible, and mutant-selective EGFR-TKIs induced by exogenous and/or endogenous HGF in EGFR mutant lung cancer cell lines, by blocking the Met/Gab1/PI3K/Akt pathway in vitro. E7050 also prevents the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF. [2]
Kinase Assay Western blot analysis
The phosphorylation status of c-Met and VEGFR-2 is detected by Western blot analysis. For c-Met, MKN45 cells are incubated with a serial dilution of E7050 in complete medium at 37 °C for 2 h. For VEGFR-2, HUVEC are starved with human endothelial serum free medium containing 0.5% FBS for 24 h. Subsequently HUVEC are incubated with a serial dilution of E7050 for 1 h and then incubated with 20 ng/mL of human VEGF for 5 min. Cells are lysed by lysis buffer (50 mM HEPES [pH 7.4], 150 mM NaCl, 10% glycerol, 1% Triton X-100, 1.5 mM MgCl2, 1 mM EDTA [pH 8.0], 100 mM NaF, 1 mM phenylmethylsulfonyl fluoride 1 mM sodium orthovanadate, 10 μg/mL aprotinin, 50 μg/mL leupeptin, and 1 μg/mL pepstatin A). The resected tumor samples are homogenized with lysis buffer containing 25 mM β-glycerophosphate and 0.5% (v/v) phosphatase inhibitor cocktail 2 at 4 °C. Cellular debris is removed by centrifugation at 17 860g for 20 min at 4 °C. Aliquots of the supernatants containing 5-20 μg of protein are subjected to SDS-PAGE under reducing conditions. The proteins are then transferred onto PVDF membranes, blocked with TBS containing 0.05% Tween-20 and either 5% skim milk or 5% BSA. The membranes are probed with the following antibodies: anti-c-Met polyclonal antibody (C-28) and anti-VEGFR-2 polyclonal antibody (C-20); mouse anti-phosphotyrosine clone 4G10; and anti-VEGFR-2 polyclonal antibody, anti-phospho-VEGFR-2 (Tyr996) polyclonal antibody, and anti-phospho-c-Met (Tyr1234/1235) polyclonal antibody. Detection is performed using a Super Signal enhanced chemiluminescence kit. Immunoreactive bands are visualized by chemiluminescence with an Image Master-VDS-CL detection system. The intensity of each band is measured by using an image analyzer.
Cell Research Cell lines MKN45, EBC-1, Hs746T, SNU-5, A549, SNU-1 and MKN74
Concentrations 5-5000 nM
Incubation Time 3 days
Method Cells (1–3 × 103 cells/100 μL/well) are seeded on 96-well culture plates with various concentrations of E7050 and cultured for 3 days. Then, 10 μL of WST-8 reagent is added to each well, and absorbance is measured at 450 nm compared with a reference measurement at 660 nm using a MTP-500 microplate reader. HUVEC (2 × 103 cells/well) are cultured for 3 days in medium containing HGF (30 ng/mL), VEGF (20 ng/mL), or basic fibroblast growth factor (bFGF) (20 ng/mL) together with serially diluted E7050.
In Vivo
In vivo In vivo studies using E7050 shows inhibition of the phosphorylation of c-Met and VEGFR-2 in tumors, and strong inhibition of tumor growth and tumor angiogenesis in xenograft models. Treatment of some tumor lines containing c-met amplifications with high doses of E7050 (50–200 mg/kg) induces tumor regression and disappearance. In a peritoneal dissemination model, E7050 shows an antitumor effect against peritoneal tumors as well as a significant prolongation of lifespan in treated mice. [1] In another xenograft model research, tumors produced by HGF-transfected Ma-1 (Ma-1/HGF) cells are more angiogenic than vector control tumors and shows resistance to ZD1839. E7050 alone inhibits angiogenesis and retards growth of Ma-1/HGF tumors. E7050 combined with ZD1839 induces marked regression of tumor growth. [3]
Animal Research Animal Models Subcutaneous xenograft models
Dosages 50–200 mg/kg
Administration orally once a day
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01355302 Terminated
Advanced or Metastatic Solid Tumors|Previously Untreated Gastric Cancer
Eisai Inc.|Quintiles Inc.
 November 2011 Phase 1|Phase 2
NCT01433991 Terminated
Advanced Solid Tumors
Eisai Inc.
 October 13 2011 Phase 1|Phase 2
NCT01332266 Completed
Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck
Eisai Inc.|PharmaBio Development Inc.
 September 19 2011 Phase 1|Phase 2
NCT01271504 Completed
Hepatocellular Carcinoma
Eisai Inc.|PharmaBio Development Inc.
 July 19 2011 Phase 1|Phase 2
NCT02533102 Completed
Healthy Subjects
Eisai Limited|Eisai Inc.
 November 2010 Phase 1
NCT00921869 Completed
Solid Tumors
Eisai Co. Ltd.|Eisai Inc.
 October 2009 Phase 1

Chemical Information & Solubility

Molecular Weight 633.69 Formula

C33H37F2N7O4
CAS No. 928037-13-2 SDF Download Golvatinib (E7050) SDF
Smiles CN1CCN(CC1)C2CCN(CC2)C(=O)NC3=NC=CC(=C3)OC4=CC(=C(C=C4)NC(=O)C5(CC5)C(=O)NC6=CC=C(C=C6)F)F
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 20 mg/mL ( (31.56 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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