Epothilone D (BMS-241027) is a macrolide compounds isolated from myxobacterium Sorangium cellulosum that acts through microtubule stabilization. Epothilones have strong antitumor activity against several human cancer cells. Although the epothilones share some similarities with the taxanes, the epothilones have significant antitumor activity against taxane-resistant human cancer cells. Taxanes have poor blood-brain barrier (BBB) permeability, while Epothilone D crosses the BBB, and in PS19 tau transgenic mice, it increased microtubule density and reduced cognitive deficits. [120] In a Phase 1 study with healthy females, Epothilone D, which had been known to produce adverse effects at higher dose in vandevoncologic trials, only produced a single Grade 3 hypersensitivity reaction [121]. A follow-up Phase 1/2 study in 40 mild AD patients given Epithilone D or placebo for 10 weeks concluded in October 2013 (NCT01492374), but results were never published and development was subsequent discontinued.
