Eg5 Inhibitors have Contrasting Effects on Microtubule Stability and Spindle Integrity Depending on their Modes of Action

The goal of this work was to investigate the mechanisms underlying different Eg5 (kinesin-5) inhibitors and to assess their effects on Eg5-mediated stabilization of dynamic microtubules. Antimitotic Eg5 inhibitors were grouped into those that bind Loop-5 and produce an ADP-like state (monastrol, STLC, ispinesib and filanesib) and those that produce a rigor-like state (BRD9876). To understand their contrasting effects on Eg5 mechanics, inhibitors were analyzed in mixed-motor gliding assays consisting of different ratios of kinesin-1 and Eg5 motors, in which Eg5 "braking" dominates motility.