Vinflunine

Names

[ Name ]:
Vinflunine

[Synonym ]:
4'-Deoxy-20'
Methyl (2β,3β,4β,5α,12β,19α)-4-acetoxy-15-[(12S,14R,16R)-16-(1,1-difluoroethyl)-12-(methoxycarbonyl)-1,10-diazatetracyclo[12.3.1.0.0]octadeca-3(11),4,6,8-tetraen-12-yl]- 3-hydroxy-16-methoxy-1-methyl-6,7-didehydroaspidospermidine-3-carboxylate
4'-Deoxy-20',20'-difluoro-8'-norvincaleukoblastine
MFCD00938122
C'-Norvincaleukoblastine,4'-deoxy-20',20'-difluoro
aspidospermidine-3-carboxylic acid, 4-(acetyloxy)-6,7-didehydro-15-[(4R,6R,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,12β,19α)-
20',20'-difluoro-3',4'-dihydrovinorelbine
Methyl (2β,3β,4β,5α,12β,19α)-4-acetoxy-15-[(12S,14R,16R)-16-(1,1-difluoroethyl)-12-(methoxycarbonyl)-1,10-diazatetracyclo[12.3.1.0.0]octadeca-3(11),4,6,8-tetraen-12-yl]-3-hydroxy-16-methoxy-1-methyl-6,7-didehydroaspidospermidine-3-carboxylate
C45H54F2N4O8
Aspidospermidine-3-carboxylic acid, 4-(acetyloxy)-6,7-didehydro-15-[(4R,6R,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,12β,19α)-
methyl (2β,3β,4β,5α,12β,19α)-4-(acetyloxy)-15-[(4R,6R,8S)-4-(1,1-difluoroethyl)-8-(methoxycarbonyl)-1,3,4,5,6,7,8,9-octahydro-2,6-methanoazecino[4,3-b]indol-8-yl]-3-hydroxy-16-methoxy-1-methyl-6,7-didehydroaspidospermidine-3-carboxylate

Biological Activity

[Description]:

Vinflunine is a new vinca alkaloid uniquely fluorinated with the properties of mitotic-arresting and tubulin-interacting activity.Target: Microtubule/TubulinThe 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]. 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 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 [3].

[Related Catalog]:

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Natural Products >> Alkaloid

Research Areas >> Cancer

[References]

[1]. Ngan, V.K., et al., Novel actions of the antitumor drugs vinflunine and vinorelbine on microtubules. Cancer Res, 2000. 60(18): p. 5045-51.

[2]. Lobert, S., et al., Vinca alkaloid-induced tubulin spiral formation correlates with cytotoxicity in the leukemic L1210 cell line. Biochemistry, 2000. 39(39): p. 12053-62.

[3]. Kruczynski, A., et al., Anti-angiogenic, vascular-disrupting and anti-metastatic activities of vinflunine, the latest vinca alkaloid in clinical development. Eur J Cancer, 2006. 42(16): p. 2821-32.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.39 g/cm3

[ Molecular Formula ]:
C₄₅H₅₄F₂N₄O₈

[ Molecular Weight ]:
816.92900

[ Exact Mass ]:
816.39100

[ PSA ]:
133.87000

[ LogP ]:
5.01950

[ Index of Refraction ]:
1.652

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds

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