Vinflunine ditartrate(BMS 710485)

Molecular Weight (MW)	1079.11
Formula	C53H66F2N4O20
CAS No.	194468-36-5 (ditartrate);
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: 100 mg/mL (103.4 mM)
Water: 66 mg/mL (68.3 mM)
Ethanol: 11 mg/mL (11.4 mM)
Solubility (In vivo)	Saline: 30 mg/mL
Synonyms	Vinflunine; Vinflunine tartrate; vinflunine ditartrate; F 12158, F12158, F-12158, BMS 710485, BMS710485, BMS-710485

Molecular Weight (MW)

1079.11

Formula

C53H66F2N4O20

CAS No.

194468-36-5 (ditartrate);

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 100 mg/mL (103.4 mM)

Water: 66 mg/mL (68.3 mM)

Ethanol: 11 mg/mL (11.4 mM)

Solubility (In vivo)

Saline: 30 mg/mL

Synonyms

Vinflunine; Vinflunine tartrate; vinflunine ditartrate; F 12158, F12158, F-12158, BMS 710485, BMS710485, BMS-710485

In Vitro	In vitro activity: 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. 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%. 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. 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> 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. Kinase Assay: 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. Cell Assay: 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.
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.
Animal model	LS174T tumor cells are injected into the spleen of BALB/C nude mice.
Formulation & Dosage	Dissolved in in a saline solution (0.9% NaCl); 20 mg/kg; i.v. injection
References	Cancer Res. 2000 Sep 15;60(18):5045-51; Biochemistry. 2000 Oct 3;39(39):12053-62; Eur J Cancer. 2006 Nov;42(16):2821-32.

In Vitro

In vitro activity: 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. 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%. 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. 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> 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.

Kinase Assay: 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.

Cell Assay: 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.

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.

Animal model

LS174T tumor cells are injected into the spleen of BALB/C nude mice.

Formulation & Dosage

Dissolved in in a saline solution (0.9% NaCl); 20 mg/kg; i.v. injection

References

Cancer Res. 2000 Sep 15;60(18):5045-51; Biochemistry. 2000 Oct 3;39(39):12053-62; Eur J Cancer. 2006 Nov;42(16):2821-32.

CAS NO:	194468-36-5
规格:	≥98%

包装	价格(元)
10mg	电议
25mg	电议
50mg	电议
100mg	电议
250mg	电议