Pirani, V., Métivier, M., Gallaud, E., Thomas, A., Ku, S., Chretien, D., Ettari, R., Giet, R., Corsi, L., Benaud, C. (2020). A novel benzodiazepine derivative that suppresses microtubule dynamics and impairs mitotic progression.  J. Cell Sci. 133(7): jcs239244.

FBrf0245384

Research paper

A novel 2,3-benzodiazepine-4 derivative, named 1g, 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 1g promotes a rapid and reversible reduction in microtubule growth. Unlike most anti-mitotic compounds, we found that 1g does not interfere directly with tubulin or perturb microtubule assembly in vitro The observation that 1g also triggers a SAC-dependent mitotic delay associated with chromosome segregation in Drosophila neural stem cells, suggests that it targets a conserved microtubule regulation module in humans and flies. Altogether, our results indicate that 1g is a novel promising anti-mitotic drug with the unique properties of altering microtubule growth and mitotic spindle organization.