Cevipabulin (TTI-237) is a potent microtubule-stabilizing agent that binds to tubulin vinblastine binding site, a typical site of binding for microtubule-destabilizing agents. It is likely that cevipabulin, similarly to other triazolopyrimidines, promotes longitudinal tubulin contacts in microtubules, which promotes stabilization of micro-tubule. Cevipabulin exhibits potent cytotoxic activity in cancer cell lines including cell line expressing a high level of P-glycoprotein. It is active in vivo in several mouse xenograft models of human cancer.
potent microtubule-stabilizing agent that binds to tubulin vinblastine binding site
Cell chemical biology, 24(6), 737-750 (2017-06-06)
Microtubule-targeting agents (MTAs) are some of the clinically most successful anti-cancer drugs. Unfortunately, instances of multidrug resistances to MTA have been reported, which highlights the need for developing MTAs with different mechanistic properties. One less explored class of MTAs are [1,2,4]triazolo[1,5-a]pyrimidines
5-Chloro-6-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-N-[(1S)-2,2,2-trifluoro-1-methylethyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine butanedioate (TTI-237) is a microtubule-active compound of novel structure and function. Structurally, it is one of a class of compounds, triazolo[1,5a]pyrimidines, previously not known to bind to tubulin. Functionally, TTI-237 inhibited the binding of [(3)H]vinblastine to tubulin, but it
The Journal of pharmacology and experimental therapeutics, 357(2), 432-450 (2016-03-17)
The microtubule (MT)-stabilizing protein tau disengages from MTs and forms intracellular inclusions known as neurofibrillary tangles in Alzheimer's disease and related tauopathies. Reduced tau binding to MTs in tauopathies may contribute to neuronal dysfunction through decreased MT stabilization and disrupted
