ELR510444 (ELR-510444) is a small molecule microtubule disruptor that directly interacts with tubulin at the colchicine-binding site, shows potent microtubule-disrupting activity.
ELR510444 treatment causes a loss of cellular microtubules and the formation of aberrant mitotic spindles and leading to mitotic arrest and apoptosis of cancer cells.
ELR510444 potently inhibited cell proliferation with an IC50 value of 30.9 nM in MDA-MB-231 cells, inhibited the rate and extent of purified tubulin assembly, and displaced colchicine from tubulin.
ELR510444 is not a substrate for the P-glycoprotein drug transporter and retains activity in βIII-tubulin-overexpressing cell lines.
ELR510444 also shows potent antitumor activity in the MDA-MB-231 xenograft model with at least a 2-fold therapeutic window.
ELR510444 (30 nM) rapidly alters endothelial cell shape, similar to the effect of the vascular disrupting agent combretastatin A4