Vinflunine Tartrate

2 years -20°C Powder, 2 weeks 4°C in DMSO, 2 months -80°C in DMSO

Administered via i.v. on days 4, 7, 11, 14, 18 and 21 after tumor cell implantation.

Leukemic L1210 cell

0-1uM

Vinflunine is solubilized in a saline solution (0.9% NaCl).

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 uM. [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 uM and 3.5 uM) 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

48 hours

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.

Vinflunine is a new vinca alkaloid uniquely fluorinated with the properties of mitotic-arresting and tubulin-interacting activity.