Epothilone D

DescriptionEpothilones are microtubule-stabilizing agents with potential anti-neoplastic actions. They are natural macrolides that have high potency in both taxane-sensitive and taxane-resistant models. Epothilone D is a desoxy form of epothilone B (Item No. 10924) that inhibits the growth of a variety of cancer cells both in vitro (IC50 values range from 0.97 to 21 nM) and in mice. Epothilone D is brain penetrant and reduces neurodegeneration in aged tau transgenic mice. Effects include improved axonal transport, decreased tau neuropathology, and reduced hippocampal neuron loss. Epothilone D also rescues microtubule defects and attenuates nigrostriatal degeneration in a mouse model of Parkinson’s disease.

UsesEpothilones are polyketide natural products that inhibit cancer cells by a mechanism similar to paclitaxel, and also are effective against paclitaxel-resistant tumours. Epothilone D is in phase I clinical testing of in patients with advanced solid tumours. Epothilone D is a cytotoxic macrolide that stabilises malignant cells'' microtubules and arrests mitosis, a characteristic it shares with other epothilones. They bind to the same hepatic sites as does paclitaxel (Taxol) in a 1:1 stoichiometric ratio of a, b-tubulin heterodimers.

PreparationBio-fermentation method Culture medium:CNST medium: KNO3 0.05%, Na2HPO4 0.025%, MgSO4·7H2O 0.1%, FeC3 0.001%, agar 2%, trace element solution 1 mL/L, pH 7.2. Autoclaved at 1×105 Pa for 20 min. M26 medium:Potato starch 8.0 g/L, soybean peptone 2.0 g/L, glucose 2.0 g/L, yeast powder 2.0 g/L, MgSO4·7H2O 1.0 g/L, CaCl2 1.0 g/L, EDTA-Fe3+ 1 mL/L, trace elements 1 mL/L, pH adjusted to 7.2 with KOH. Initial Fermentation Medium:Dextrin 0.3%, sucrose 0.07%, glucose 0.02%, soybean meal 0.17%, magnesium sulfate heptahydrate 0.17%, anhydrous calcium chloride 0.3%, EDTA-Fe3+ 2 mL/L, trace elements (TE) 0.5 mL/L, pH 7.2, resin XAD-16 2%. Autoclaved at 1×105 Pa for 20 min. Cultivation Method> Seed Culture:The inoculum preserved in solid slant medium was inoculated onto CNST plates containing sterilized filter paper. The plates were inverted and cultured at 30℃ for 5-7 days. Then, the culture was transferred to M26 medium in 50 mL/250 mL Erlenmeyer flasks and cultured on a shaker at 30℃ and 170 r/min for 72 h to obtain the seed culture for fermentation. Fermentation culture:The obtained seed liquid was inoculated into the fermentation medium at an inoculation rate of 5% (V/V) and cultured on a shaker. The fermentation system consisted of 300 mL Erlenmeyer flasks containing 50 mL of liquid. The culture was carried out on a shaker at 30℃ and 170 r/min for 5 days.