Ixabepilone (Azaepothilone B) is an orally bioavailable microtubule inhibitor. It binds to tubulin and promotes tubulin polymerization and microtubule stabilization, thereby arresting cells in the G2-M phase of the cell cycle and inducing tumor cell apoptosis.

BMS-247550是一种高效的细胞毒性化合物，能以低纳摩尔浓度杀死癌细胞，同时对本身对紫杉醇不敏感或已对紫杉醇产生抗药性的人类癌症保持其抗肿瘤活性[1]。

在体内，Ixabepilone 已明显显示出其抗肿瘤活性优于紫杉醇，在对紫杉醇既敏感又抗性的肿瘤上均是如此。相较于紫杉醇，Ixabepilone 在所有五种评估的紫杉醇抗性肿瘤（四种人类和一种鼠类）中表现出更高的效能，具体包括：临床衍生的紫杉醇抗性Pat-7卵巢癌、由于微管蛋白突变而对紫杉醇产生抗性的A2780Tax卵巢癌、HCT116/VM46 MDR结肠癌、临床衍生的紫杉醇抗性Pat-21乳腺癌和鼠类成纤维细胞肉瘤M5076。在三种对紫杉醇敏感的人体肿瘤异种移植模型中，Ixabepilone产生的抗肿瘤活性与紫杉醇相当，即A2780人卵巢癌、HCT116和LS174T人结肠癌[1]。

The potency with which BMS-247550 and paclitaxel polymerize tubulin isolated from calf brain is evaluated by Published techniques. Briefly, different concentrations of paclitaxel or BMS-247550 in polymerization buffer [0.1?M mes, 1 mM?EGTA, 0.5 mM?MgCl2 (pH 6.6)] are added to tubulin in polymerization buffer at 37°C in microcuvette wells of a Beckman. Model DU 7400 UV spectrophotometer. A final microtubule protein concentration of 1.0 mg/mL and compound concentrations of generally 2.5, 5.0, and 10 μM?are used. Initial slopes of absorbance (A280 nM) change, measured every 10 s, are calculated by the software program accompanying the instrument.

HCT116 cells from cultures are collected by trypsinization after 1, 2, 4, 8, 16, and 24 h exposure to 7.5 nm of BMS-247550. Cells are pelleted and fixed in 80% ethanol at −20°C. After an overnight storage at −20°C, cells are rehydrated with PBS buffer and DNA stain by incubation with propidium iodide (5 μg/ml) in 0.1% RNase for 15–30 min. Fluorescence-activated cell sorter acquisition is performed using the FACS Calibur instrument and analysis is done using Cellquest and Modfit software. (Only for Reference)