An inhibitor of tubulin polymerization
Microtubules are involved in nucleic and cell organization, division of intracellular structure, and intracellular transport, as well as ciliary and flagellar motility. Microtubule-targeting agents are some of the most effective chemotherapeutic drugs used in the clinic today. ELR510444 is a novel microtubule disruptor with multiple mechanisms of action.
In vitro: ELR510444 has potent microtubuledisrupting activity, causing a loss of intracellular microtubules and the formation of aberrant mitotic spindles and leading to mitotic arrest and apoptosis of cancer cells. ELR510444 inhibited cell proliferation, inhibited the rate and extent of purified tubulin assembly potently, and displaced colchicine from tubulin, revealing that the drug directly interacts with tubulin at the colchicine-binding site [1].
In vivo: ELR510444 also shows potent antitumor activity in the MDA-MB-231 xenograft model with at least a 2-fold therapeutic window [1].
Clinical trial: Up to now, ELR510444 is still in the preclinical development stage.
Reference:
[1] Risinger AL, Westbrook CD, Encinas A, Mülbaier M, Schultes CM, Wawro S, Lewis JD, Janssen B, Giles FJ, Mooberry SL.? ELR510444, a novel microtubule disruptor with multiple mechanisms of action. J Pharmacol Exp Ther. 2011 Mar;336(3):652-60.
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