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, 1g does not interfere directly with tubulin, nor perturbs microtubules assembly in vitro The observation that 1g also triggers a SAC-dependent mitotic delay associated with chromosome segregation in Drosophila neural stem cells, suggests it targets a conserved microtubules regulation module in human and flies. Altogether, our results indicate that 1g is a novel promising antimitotic drug with the unique properties altering microtubules growth and mitotic spindle organization.

A novel benzodiazepine derivative that suppresses microtubules dynamics and impairs mitotic progression / Pirani, V; Métivier, M; Gallaud, E; Thomas, A; Ku, S; Chretien, D; Ettari, R; Giet, R; Corsi, L; Benaud, C4.. - In: JOURNAL OF CELL SCIENCE. - ISSN 0021-9533. - 133:7(2020), pp. 1-20. [10.1242/jcs.239244]

A novel benzodiazepine derivative that suppresses microtubules dynamics and impairs mitotic progression

Corsi L
;
2020

Abstract

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, 1g does not interfere directly with tubulin, nor perturbs microtubules assembly in vitro The observation that 1g also triggers a SAC-dependent mitotic delay associated with chromosome segregation in Drosophila neural stem cells, suggests it targets a conserved microtubules regulation module in human and flies. Altogether, our results indicate that 1g is a novel promising antimitotic drug with the unique properties altering microtubules growth and mitotic spindle organization.
2020
24-feb-2020
133
7
1
20
A novel benzodiazepine derivative that suppresses microtubules dynamics and impairs mitotic progression / Pirani, V; Métivier, M; Gallaud, E; Thomas, A; Ku, S; Chretien, D; Ettari, R; Giet, R; Corsi, L; Benaud, C4.. - In: JOURNAL OF CELL SCIENCE. - ISSN 0021-9533. - 133:7(2020), pp. 1-20. [10.1242/jcs.239244]
Pirani, V; Métivier, M; Gallaud, E; Thomas, A; Ku, S; Chretien, D; Ettari, R; Giet, R; Corsi, L; Benaud, C4.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1199340
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