Spastazoline is a potent, selective, cell-permeable, ATP-competitive inhibitor of human Spastin, inhibits the steady-state ATPase activity of the Hs-spastin with IC50 of 99 nM.
Spastazoline does not appreciably inhibit any of the four related AAA proteins (Xl-katanin, Hs-FIGL1, Mm-VCP and Hs-PCH2) at 10 uM, also does not inhibit ATPase activity of recombinant human VPS4.
Spastazoline inhibited Hs-spastin-N386C mutant >100-fold less potently than the wild-type protein; causes a ~2-fold increase in the number of cells with intercellular bridges in treated HeLa-WT cells with spastazoline (4.5h at 10 µM) without effect on the viability and organization of microtubulesof HeLa cell.
Inhibition of spastin activity probably suppresses microtubule severing and thereby impairs spastin dissociation and the loss of ESCRT-III from the sites of membrane constriction; Spastazoline is a valuable probe spastin’s function in dynamic cellular processes.