Utidelone

Utidelone (Epothilone D) is a potent microtubule stabilizer. IC50 & Target:Microtubule/Tubulin^[1] In Vitro:Utidelone (Epothilone D) is a more potent microtubule stabilizer in vitro than epothilone A or B. In vitro, Utidelone has shown potent cytotoxicity in a panel of human tumor cell lines, with similar potency to paclitaxel. Utidelone also shows a definite advantage over paclitaxel in drug-resistant cell lines, and retained its cytotoxicity against a multidrug resistant cell line over-expressing P-glycoprotein^[1].
Utidelone is a microtubules (MTs)-stabilizing agent^[2]. In Vivo:To evaluate whether Utidelone (Epothilone D) improves MT and axonal function in PS19 mice, groups of 3-month old male PS19 mice received weekly i.p. injections of vehicle or Utidelone (1 mg/kg or 3 mg/kg) for a total of 3 months. In addition, 3-month old non-Tg littermates received 3 mg/kg Utidelone or vehicle. The 3 mg/kg Utidelone dose corresponds to ~10-fold less than that used in a Phase II clinical study, which should minimize side-effects such as neutropenia that are observed with MT-stabilizing drugs in human subjects. PS19 and WT mice that receive Utidelone show no signs of drug intolerance. Indeed, all drug-treated mice exhibited weight gain that is indistinguishable from vehicle-treated animals. Likewise, relative organ weights are similar in vehicle- and Utidelone-treated mice. The motor performance of Utidelone-treated mice, assessed using a standard rotarod test, is not significantly different from vehicle-treated cohorts. Finally, although there is minor group-to-group variability, there are no significant differences in white blood cell counts or neutrophil content between any of the treatment cohorts. Thus, the low doses of Utidelone utilized in these studies appeared to be well tolerated^[2].