Golvatinib (E7050)

Catalog No.S2859 Batch:S285901

Print

Technical Data

Formula

C33H37F2N7O4
Molecular Weight 633.69 CAS No. 928037-13-2
Solubility (25°C)* In vitro DMSO 20 mg/mL (31.56 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
30%propylene glycol 5%Tween80 65%D5W

Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.

 30.000mg/ml (47.34mM) Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified propylene glycol stock solution to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Golvatinib (E7050) is a dual c-Met and VEGFR-2 inhibitor with IC50 of 14 nM and 16 nM, respectively. This compound does not inhibit bFGF-stimulated HUVEC growth (up to 1000 nM) and is currently in Phase 1/2 trials.
Targets
c-Met [1] VEGFR2 [1]
14 nM 16 nM
In vitro In vitro studies indicate that Golvatinib (E7050) potently inhibits phosphorylation of both c-Met and VEGFR-2. It also potently represses the growth of both c-met amplified tumor cells and endothelial cells stimulated with either HGF or VEGF. [1] This compound 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. It also prevents the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF. [2]
In vivo Golvatinib (E7050) shows inhibition of the phosphorylation of c-Met and VEGFR-2 in tumors in vivo, with strong suppression of tumor growth and angiogenesis in xenograft models. Treatment of some tumor lines containing c-met amplifications with high doses of this compound (50–200 mg/kg) induces tumor regression and disappearance. In a peritoneal dissemination model, it demonstrates an antitumor effect against peritoneal tumors as well as a significant prolongation of lifespan in treated mice. [1] In another xenograft study, tumors produced by HGF-transfected Ma-1 (Ma-1/HGF) cells are more angiogenic than vector control tumors and show resistance to ZD1839. E7050 alone inhibits angiogenesis and retards growth of Ma-1/HGF tumors, and when combined with ZD1839, it induces marked regression of tumor growth. [3]

Protocol (from reference)

Kinase Assay:[1]
  • 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 Golvatinib (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 this compound 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 Assay:[1]
  • 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 Golvatinib (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 this compound.
Animal Study:[1]
  • Animal Models

    Subcutaneous xenograft models

  • Dosages

    50–200 mg/kg

  • Administration

    orally once a day

References

  • https://pubmed.ncbi.nlm.nih.gov/19832844/
  • https://pubmed.ncbi.nlm.nih.gov/22317763/
  • https://pubmed.ncbi.nlm.nih.gov/22789825/

Customer Product Validation

PC-9/LMC-GR cells (2 × 105 cells/well) were incubated in 6-well plates with various concentrations of gefitinib with or without crizotinib (1 μmol/L) or golvatinib (1 μmol/L) for 1 hour. Cell lysate were obtained and subjected to immunoblotting with antibodies toward the indicated molecules.

Data from [ , , Mol Cancer Ther, 2017, 16(3):506-515 ]

B, PC-9/LMC-GR cells (2 × 105 cells/well) were incubated in 6-well plates with various concentrations of gefitinib with or without crizotinib (1 μmol/L) or golvatinib (1 μmol/L) for 1 hour. Cell lysate were obtained and subjected to immunoblotting with antibodies toward the indicated molecules.

Data from [ , , Mol Cancer Ther, 2017, 16(3):506-515 ]

SBC-5, DMS273, and DMS273-G3H cells were treated with either 1 lM crizotinib or golvatinib for 2 h. Cell lysates were evaluated for protein expression by Western blot analysis. Three independent experiments were carried out, and a representative result is shown. p, phosphorylated.

Data from [ , , Cancer Sci, 2017, 108(7):1378-1385 ]

Selleck's Golvatinib (E7050) Has Been Cited by 8 Publications

E7050 Suppresses the Growth of Multidrug-Resistant Human Uterine Sarcoma by Inhibiting Angiogenesis via Targeting of VEGFR2-Mediated Signaling Pathways [ Int J Mol Sci, 2023, 24(11)9606] PubMed: 37298555
Blockade of c-Met-Mediated Signaling Pathways by E7050 Suppresses Growth and Promotes Apoptosis in Multidrug-Resistant Human Uterine Sarcoma Cells [ Int J Mol Sci, 2022, 23(23)14884] PubMed: 36499211
MET amplification results in heterogeneous responses to osimertinib in EGFR-mutant lung cancer treated with erlotinib [ Cancer Sci, 2020, 111(10):3813-3823] PubMed: 32735723
Diverse Receptor Tyrosine Kinase Phosphorylation in Urine-Derived Tubular Epithelial Cells from Autosomal Dominant Polycystic Kidney Disease Patients [ Nephron, 2020, 1-12] PubMed: 32799196
LECT2, a Ligand for Tie1, Plays a Crucial Role in Liver Fibrogenesis [ Cell, 2019, 178(6):1478-1492] PubMed: 31474362
MET Copy Number Gain Is Associated with Gefitinib Resistance in Leptomeningeal Carcinomatosis of EGFR-mutant Lung Cancer [Nanjo S Mol Cancer Ther, 2017, 16(3):506-515] PubMed: 28138027
Impact of MET inhibition on small-cell lung cancer cells showing aberrant activation of the hepatocyte growth factor/MET pathway. [Taniguchi H, et al. Cancer Sci, 2017, 108(7):1378-1385] PubMed: 28474864
In vivo imaging xenograft models for the evaluation of anti-brain tumor efficacy of targeted drugs [Kita K Cancer Med, 2017, 6(12):2972-2983] PubMed: 29125233

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.