A novel benzodiazepine derivative that suppresses microtubule dynamics and impairs mitotic progression.

A novel 2,3-benzodiazepine-4 derivative, named 1, has recently been shown to function as an anti-proliferative compound. We now show that it perturbs the formation of a functional mitotic spindle, inducing a spindle assembly checkpoint (SAC)-dependent arrest in human cells. Live analysis of individual microtubules indicates that 1 promotes a rapid and reversible reduction in microtubule growth. Unlike most anti-mitotic compounds, we found that 1 does not interfere directly with tubulin or perturb microtubule assembly The observation that 1 also triggers a SAC-dependent mitotic delay associated with chromosome segregation in neural stem cells, suggests that it targets a conserved microtubule regulation module in humans and flies. Altogether, our results indicate that 1 is a novel promising anti-mitotic drug with the unique properties of altering microtubule growth and mitotic spindle organization.