The binding sites of microtubule-stabilizing agents.

Microtubules (MTs) are a highly successful target for anticancer therapy. MT-stabilizing agents (MSAs) bind to MTs, promoting their polymerization, blocking mitosis, and causing cell death. There are currently four clinically important MSAs, with many others in preclinical and clinical development. MTs have three binding sites for these compounds; however, the exact locations and drug-protein interactions of these sites are still controversial. This review will describe the possible binding sites, the compounds that bind to them, and the effect of this binding on MT function. The binding site of an MSA on tubulin is important for characterizing the compound as an anticancer agent and provides insight not only into possible synergistic interactions with other compounds but also on the MSA "pharmacophore." This information can aid in the design of novel MSAs with improved properties.