Differentiating between models of epothilone binding to microtubules using tubulin mutagenesis, cytotoxicity, and molecular modeling.

Microtubule stabilizers are powerful antimitotic compounds and represent a proven cancer treatment strategy. Several classes of compounds in clinical use or trials, such as the taxanes and epothilones, bind to the same region of β-tubulin. Determining how these molecules interact with tubulin and stabilize microtubules is important both for understanding the mechanism of action and enhancing chemotherapeutic potential, for example, minimizing side effects, increasing solubility, and overcoming resistance.