Antibodies
Golvatinib (E7050)
- 貨號 Cat. No.
- S2859
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
Golvatinib (E7050)
Catalog No.S2859
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.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
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. | |||||
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| Targets | c-Met | VEGFR-2 | ||||
| IC50 | 14 nM | 16 nM [1] | ||||
| 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] | |||||
| 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] | |||||
| Features | ||||||
Protocol(Only for 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 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. |
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Cell Assay: [1]
| Cell lines | MKN45, EBC-1, Hs746T, SNU-5, A549, SNU-1 and MKN74 |
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| 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. |
Animal Study: [1]
| Animal Models | Subcutaneous xenograft models |
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| Dosages | 50–200 mg/kg |
| Administration | orally once a day |
| Solubility | 30% propylene glycol, 5% Tween 80, 65% D5W, 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01271504 | Recruiting | Hepatocellular Carcinoma | Eisai Inc.|PharmaBio Development Inc. | 2011-04 | Phase 1|Phase 2 |
| NCT01332266 | Recruiting | Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck | Eisai Inc.|PharmaBio Development Inc. | 2011-05 | Phase 1|Phase 2 |
| NCT01428141 | Recruiting | Solid Tumor|Gastric Cancer | Eisai Inc.|Eisai Co., Ltd. | 2011-09 | Phase 1 |
| NCT01433991 | Recruiting | Advanced Solid Tumors | Eisai Inc. | 2011-10 | Phase 1|Phase 2 |
| NCT01355302 | Terminated | Advanced or Metastatic Solid Tumors|Previously Untreated Gastric Cancer | Eisai Inc.|PharmaBio Development Inc. | 2011-11 | Phase 1|Phase 2 |
Chemical Information
Download Golvatinib (E7050) SDF
| Molecular Weight (MW) | 633.69 |
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| Formula | C33H37F2N7O4 |
| CAS No. | 928037-13-2 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 20 mg/mL (31 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| In vivo | 30% propylene glycol, 5% Tween 80, 65% D5W, | 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 | 1,1-Cyclopropanedicarboxamide, N-[2-fluoro-4-[[2-[[[4-(4-methyl-1-piperazinyl)-1-piperidinyl]carbonyl]amino]-4-pyridinyl]oxy]phenyl]-N-(4-fluorophenyl)- |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
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| Mass(mg) | 0.63369 | 6.3369 | 12.6738 | 19.0107 |
