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].
[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.