Ixabepilone 是一种可口服的微管抑制剂，能够与微管蛋白结合，促进微管蛋白的聚合和微管的稳定，使细胞停滞在 G2-M 期，诱导细胞凋亡。

Ixabepilone 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 is a highly potent cytotoxic agent capable of killing cancer cells at low nanomolar concentrations as well as retains its antineoplastic activity against human cancers that are naturally insensitive to paclitaxel or that have developed resistance to paclitaxel[1].

In vivo, BMS-247550 has clearly demonstrated antitumor activity that is superior to paclitaxel in both paclitaxel-resistant and -sensitive tumors. BMS-247550 is more efficacious compared to paclitaxel in all five paclitaxel-resistant tumors evaluated in this study (four human and one murine): i.e., the clinically derived paclitaxel resistant Pat-7 ovarian carcinoma, the A2780Tax ovarian carcinoma that is resistant to paclitaxel because of tubulin mutations, the HCT116/VM46 MDR colon carcinoma, the clinically derived paclitaxel-resistant Pat-21 breast carcinoma, and the murine fibrosarcoma M5076. Against three paclitaxel-sensitive human tumor xenografts, BMS-247550 produces antitumor activity equivalent to paclitaxel: i.e., A2780 human ovarian carcinoma, HCT116, and LS174T human colon carcinoma[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)

219989-84-1

C27H42N2O5S

506.7

Azaepothilone B;Ixempra;BMS 247550-1;BMS 247550;伊沙匹隆

Ethanol:93 mg/mL (183.5 mM)
DMSO:93 mg/mL (183.5 mM)
H2O:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years