"目录号: HY-15278
Cell Cycle/DNA DamageCytoskeleton-
Epothilone D 是一种有效的微管 (microtubule) 稳定剂。
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生物活性
Description
Epothilone D is a potentmicrotubulestabilizer.
IC50& Target
Microtubule/Tubulin[1]
In Vitro
Epothilone D (KOS-862) is a more potent microtubule stabilizer in vitro than epothilone A or B. In vitro, Epothilone D has shown potent cytotoxicity in a panel of human tumor cell lines, with similar potency to paclitaxel. Epothilone D 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]. Epothilone D (EpoD) is a microtubules (MTs)-stabilizing agent[2].
In Vivo
To evaluate whether Epothilone D (EpoD) improves MT and axonal function in PS19 mice, groups of 3-month old male PS19 mice received weekly i.p. injections of vehicle or Epothilone D (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 Epothilone D or vehicle. The 3 mg/kg Epothilone D 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 Epothilone D 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 Epothilone D-treated mice. The motor performance of Epothilone D-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 Epothilone D utilized in these studies appeared to be well tolerated[2].
Clinical Trial
Bristol-Myers Squibb
Neoplasms
October 2001
Phase 1
Memorial Sloan Kettering Cancer Center-National Cancer Institute (NCI)
Colorectal Cancer
October 2003
Phase 2
Memorial Sloan Kettering Cancer Center-National Cancer Institute (NCI)
Lung Cancer
December 2003
Phase 2
Hoffmann-La Roche
Breast Cancer
May 2004
Phase 2
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References
