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Epothilone D

Cat. No. M6278
Epothilone D Structure
Size Price Availability Quantity
10mg USD 300 In stock
25mg USD 650 In stock
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Quality Control
  • Current batch:
  • Purity >98%
  • COA
  • MSDS
Biological Activity

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. Epothilone D (EpoD) is a microtubules (MTs)-stabilizing agent.

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.

Protocol
Cell Experiment
Cell lines
Preparation method
Concentrations
Incubation time
Animal Experiment
Animal models Mice
Formulation dissolved in 100% DMSO and diluted with saline or PBS
Dosages 3 mg/kg
Administration i.p.
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 491.68
Formula C27H41NO5S
CAS Number 189453-10-9
Purity >98%
Solubility 10 mM in DMSO
Storage at -20°C
References

Highly Efficient CYP167A1 (EpoK) dependent Epothilone B Formation and Production of 7-Ketone Epothilone D as a New Epothilone Derivative.
Kern F, et al. Sci Rep. 2015 Oct 8;5:14881. PMID: 26445909.

The microtubule-stabilizing drug Epothilone D increases axonal sprouting following transection injury in vitro.
Brizuela M, et al. Mol Cell Neurosci. 2015 May;66(Pt B):129-40. PMID: 25684676.

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Keywords: Epothilone D supplier, Microtubule, inhibitors

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