Vinflunine Tartrate, a uniquely fluorinated vinca alkaloid, exhibits mitotic-arresting and tubulin-interacting properties.

Vinflunine对微管动态不稳定性的主要影响包括微管生长速率的减缓、生长持续时间的增加以及缩短持续时间的减少。通过跟踪[3H]GTP合并到富含MAP的微管中来检查Vinflunine对重铣速率的影响，其IC50为0.42 μM。[1] Vinflunine引发的有丝分裂积累的IC50为18.8 nM，它通过降低着丝点的动态性44%并增加着丝点处于暂停状态的时间63%。[2] Vinflunine ditartrate显示对微管的抑制（纯化的tubulin和MTP）以及对L1210细胞的细胞毒性，其IC50分别为（0.49 μM和3.5 μM）和97 nM。[3] Vinflunine通过后有丝分裂G1阻滞和线粒体途径以浓度依赖性方式在神经母细胞瘤SK-N-SH细胞中诱导凋亡，IC50为50 nM。[4] Vinflunine处理导致内皮细胞形状迅速变化：细胞收缩并呈现圆形形态。对于纤维连接蛋白和IV型胶原蛋白，平均IC50值分别为9.9 x 10^-5 M和5.0 x 10^-5 M。短暂地将内皮细胞暴露于10^-8至10^-4 M的Vinflunine中，可抑制内皮细胞对NIH3T3细胞衍生的血管生成因子的运动反应。抑制作用呈剂量依赖性，平均IC50值为7.1 x 10^-7 M。[5]

小鼠经静脉给予Vinflunine治疗，具体时点为Matrigel植入前即刻以及之后2天，可见到对bFGF诱发的血管生成反应的剂量依赖性抑制。在1.25、2.5和5 mg/kg的剂量下，Vinflunine 对血红蛋白含量的抑制显著，而在0.63 mg/kg的剂量下无效（P > 0.05）。Vinflunine的低剂量能减少由人类LS174T结肠癌细胞引起的实验性肝转移数量。在极低剂量0.16 mg/kg Vinflunine下即可观察到肝转移灶的轻微总体减少，尽管在最大耐受剂量（MTD）20 mg/kg时达到最大总体抑制。[5]

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.

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.(Only for Reference)