189453-10-9
189453-10-9 结构式
基本信息
埃博霉素
埃博霉素D
埃坡西龙 D
埃博霉素D 埃坡西龙 D
埃博霉素 D(埃坡西龙 D、埃博霉素D、爱博霉素D)
KOS 862
NSC 703147
Epothilone D
Desoxyepothilone B
12,13-Desoxyepothilone B
(4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-5,5,7,9,13-pentaMethyl-16-[(1E)-1-Methyl-2-(2-Methyl-4-thiazolyl)ethenyl]oxacyclohexadec-13-ene-2,6-dione
(3S,7S,14S,15S,16R)-3,15-Dihydroxy-2,2,10,14,16-pentamethyl-7-[1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-6-oxacyclohexadec-9-ene-1,5-dione
Oxacyclohexadec-13-ene-2,6-dione, 4,8-dihydroxy-5,5,7,9,13-pentamethyl-16-(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl-, (4S,7R,8S,9S,13Z,16S)-
Oxacyclohexadec-13-ene-2,6-dione, 4,8-dihydroxy-5,5,7,9,13-pentamethyl -16-(1-methyl-2-(2-methyl-4-thiazolyl)ethenyl)-, (4S-(4R*,7S,8R*,9R*,1 3Z,16R*(E)))-
物理化学性质
常见问题列表
图1为埃博霉素B结构式
培养基：CNST 培养基：KNO30.05%，Na2HPO40.025%，MgSO4·7H2O 0.1%，FeC30.001%，琼脂 2%，微量元素液 1 mL/L，pH7.2。1×105Pa 高压蒸汽灭菌 20 min。
M26培养基：土豆淀粉 8.0 g/L，大豆蛋白胨 2.0g/L，葡萄糖 2.0 g/L，酵母粉 2.0 g/L，MgSO4·7H2O1.0 g/L，CaCl21.0 g/L，EDTA-Fe3+1 mL/L，微量元素1 mL/L，以 KOH 调节 pH 值为 7.2。
初始发酵培养基：糊精 0.3%，蔗糖 0.07%，葡萄糖 0.02%，豆饼粉 0.17%，七水硫酸镁 0.17%，无水氯化钙 0.3%，EDTA-Fe3+2 mL/L，微量元素（TE）0.5 mL/L，pH7.2，树脂 XAD-16 2%。1×105Pa 高压蒸汽灭菌 20 min。
培养方法
种子培养：：将保藏在固体斜面培养基的菌种接入放有已灭菌滤纸片的 CNST 平板上，倒置于恒温培养箱中在 30℃条件下培养 5-7 d 后，转接于 M26 培养基中，装液量为 50 mL/250 mL 三角瓶，在 30℃、170 r/min 的条件下摇床培养 72 h 后，得到作为发酵培养的种子液。
发酵培养：以 5%（V/V）接种量将所得种子液接种到发酵培养基中进行摇床培养，发酵体系为300 mL 三角瓶装液量为 50 mL，在 30℃、170 r/min的条件下摇床培养 5 d。
有关埃博霉素B的概述、制备方法、应用是由Chemicalbook的丁红编辑整理。（2015-12-21）
Microtubule/Tubulin
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.
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 (EpoD) (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 (EpoD) or vehicle. The 3 mg/kg Epothilone D (EpoD) 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 (EpoD) 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 (EpoD)-treated mice. The motor performance of Epothilone D (EpoD)-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 (EpoD) utilized in these studies appeared to be well tolerated.