Antibodies
Vinflunine Tartrate
- 貨號 Cat. No.
- S2209
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
Vinflunine Tartrate
Catalog No.S2209
Vinflunine is a new vinca alkaloid uniquely fluorinated with the properties of mitotic-arresting and tubulin-interacting activity. Phase 2/3.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | Vinflunine is a new vinca alkaloid uniquely fluorinated with the properties of mitotic-arresting and tubulin-interacting activity. Phase 2/3. | |||||
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| Targets | Microtubule | |||||
| IC50 | 1.2 μM [1] | |||||
| In vitro | The major effects of Vinflunine on dynamic instability are a slowing of the microtubule growth rate, an increase in growth duration, and a reduction in shortening duration. The effects of Vinflunine on the readmilling rate is examined by following [3H]GTP incorporation into MAP-rich microtubules, and the IC50 is 0.42 μM. [1] Vinflunine induced mitotic accumulation with IC50 with 18.8 nM, which decreases the centromere dynamicity by 44% and increases the time centromeres spent ina paused state by 63%. [2] Vinflunine ditartrate exhibits microtubule inhibition (purified tubulin and MTP) and cytotoxicity in L1210 cells with IC50 of (0.49 μM and 3.5 μM) and 97 nM, respectively. [3] Vinflunine induces apoptosis in neuroblastoma SK-N-SH cells through a postmitotic G1 arrest and a mitochondrial pathway in a concentration-dependent manner with an IC50 with 50 nM. sup>[4] Treatment of Vinflunine induces a rapid change in endothelial cell shape: cells retracts and assumes a rounded morphology. Mean IC50 values are 9.9 × 10-5 M × 10-5 M for fibronectin and 5.0× 10-5 M × 10-5 M for type IV collagen. A short 4 hours exposure of endothelial cells to Vinflunine at 10-8-4 M results in an inhibition of endothelial cell motility response to NIH3T3 cells-derived angiogenic factors. Inhibition is dose dependent, with a mean IC50 value of 7.1 × 10-7 × 10-7 M. [5] | |||||
| In vivo | Intravenous treatment of mice with Vinflunine, immediately before and 2 day after Matrigel implantation, results in a dose-dependent inhibition of the bFGF-induced angiogenic response, compared with vehicle-treated animals. Inhibition of haemoglobin content is significant at 1.25, 2.5 and 5 mg/kg, with no effect at 0.63 mg/kg (P > 0.05). An ID50 value (dose which inhibits 50% of bFGF-induced neovascularisation) is calculated as 1 mg/kg. Low doses of Vinflunine reduce the number of experimental liver metastases by human LS174T colon cancer cell. A slight overall decrease in liver metastatic foci is already observed at the very low dose of 0.16 mg/kg Vinflunine, although maximal overall inhibition is reached at the maximal tolerated dose (MTD) of 20 mg/kg. [5] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [1]
| Determination of Microtubule Polymer Mass | Purified tubulin (17 μM) is polymerized into microtubules in the abence or presence of a range of vnflunine concentrations (35 minutes; 37 °C) in 75 mM PIPES, 1.8 mM MgCl2, 1.0 mM EGTA, and 1.5 mM GTP (pH 6.8) using sea urchin (Strongylocentrotus purpuratus) axonemes as seeds for assembly initiation. After incubation, polymerized microtubules are separated from unpolymerized tubulin by centrifugation (150,000 × g; 1 hour; 35 °C). The supernatant is aspirated, the sedimented microtubules are depolymerized in assembly buffer by incubation on ice (2 hours), and the protein content is determined. |
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| Microtubule Inhibition | PC-tubulin (1.8 mg/mL) is polymerized in 100 mM MES, pH 6.9, 10 mM MgSO4, 2 mM EGTA, 1 mM GTP, and 2 M glycerol Experiments are carried out in the presence and absence of test compounds over concentration ranges of 0.1 to 1 μM. Microtubule formation is monitored using a Gilford Response II UV-Vis or a Varian Cary 3E scanning spectrophotometer equipped with a cooling Peltier cell holder. Prior to polymerization, samples are degassed on ice for 30 minutes, and baseline data are collected at 4 °C and 350 nm. The temperature is increased to 37 °C, and solutions are monitored at 350 nm for 45 minutes. Solutions are cooled to 0 °C, and a second baseline is recorded. The change in optical density is plotted vs compound concentration after subtracting the second baseline from the plateau optical density at 45 minutes. This ΔOD corresponds to the temperature-sensitive reversible polymerization and corrects for irreversible aggregation. The percent inhibition is calculated relative to the control sample. The IC50 concentration (drug concentration causing 50% inhibition of microtubule assembly) is determined from the mean of three independent experiments. |
Cell Assay: [3]
| Cell lines | Leukemic L1210 cell |
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| Concentrations | 0-1μM |
| Incubation Time | 48 hours |
| Method | Effects of Vinflunine on L1210 cell proliferation are determined using a standard growth inhibition assay. Exponentially growing L1210 cells (1.5 × 105 cells/well) in a 24-well plate are exposed to a range of concentrations of test compounds for 48 hours, prior to determining cell numbers using an electronic particle counter based on linear interpolation between data points. |
Animal Study: [5]
| Animal Models | LS174T tumor cells are injected into the spleen of BALB/C nude mice. |
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| Dosages | ~20 mg/kg |
| Administration | Administered via i.v. on days 4, 7, 11, 14, 18 and 21 after tumor cell implantation. |
| Solubility | Saline, 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01265940 | Completed | Advanced Urothelial Cancer of Bladder After Failure of Platinum-containing Therapy. | Lukas-Krankenhaus GmbH|Prof. Dr. Thomas Otto | 2011-03 | Phase 1|Phase 2 |
| NCT01529411 | Not yet recruiting | Carcinoma, Transitional Cell | Spanish Oncology Genito-Urinary Group | 2012-02 | Phase 2 |
| NCT01844947 | Recruiting | Urothelial Cancer|Bladder Cancer|Renal Pelvis Cancer|Ureter Cancer|Urethra Cancer | Karolinska University Hospital|Dr Anders Ull茅n|Bayer|Pierre Fabre Laboratories|Nordic Urothelial Cancer Oncology Group | 2012-06 | Phase 1 |
| NCT01830231 | Recruiting | Urothelium Transitional Cell Carcinoma | Associaciè´¸ per a la Recerca Oncologica, Spain | 2012-10 | Phase 2|Phase 3 |
| NCT01953003 | Recruiting | Malignant Neoplasm of Breast | Pierre Fabre Medicament | 2013-09 | Phase 3 |
Chemical Information
Download Vinflunine Tartrate SDF
| Molecular Weight (MW) | 967.02 |
|---|---|
| Formula | C45H54F2N4O8.xC4H6O6 |
| CAS No. | 1201898-17-0 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 193 mg/mL (199 mM) |
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| Water | 193 mg/mL (199 mM) | ||
| Ethanol | 193 mg/mL (199 mM) | ||
| In vivo | Saline, | 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 | Aspidospermidine-3-carboxylic acid, 4-(acetyloxy)-6,7-didehydro-15-[(2R,4R,6S,8S)-4-(1,1-difluoroethyl)-1,3,4,5,6,7,8,9-octahydro-8-(methoxycarbonyl)-2,6-methano-2H-azecino[4,3-b]indol-8-yl]-3-hydroxy-16-methoxy-1-methyl-, methyl ester, (2β,3β,4β,5α,12R,19β)-, (2R,3R)-2,3-dihydroxybutanedioate (1:x) |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
|---|---|---|---|---|
| Mass(mg) | 0.96702 | 9.6702 | 19.3404 | 29.0106 |
