1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEEpothilone DCat. No.: HY-15278CAS No.: 189453-10-9Synonyms: KOS 862分式: CHNOS分量: 491.68作靶點(diǎn): Microtubule/Tubulin作通路: Cell Cycle/DNA Damage; Cytoskeleton儲存式: Powder -20C 3 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 3

2、20 mg/mL (650.83 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.0338 mL 10.1692 mL 20.3384 mL5 mM 0.4068 mL 2.0338 mL 4.0677 mL10 mM 0.2034 mL 1.0169 mL 2.0338 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Epothilone D (KOS 862)

3、是有效的微管穩(wěn)定劑。IC50 & Target Microtubule/Tubulin 1體外研究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 to1/3 Master of Small Molecules 您邊的抑制劑師www.M

4、edChemEpaclitaxel. Epothilone D also shows a definite advantage over paclitaxel in drug-resistant cell lines, andretained its cytotoxicity against a multidrug resistant cell line over-expressing P-glycoprotein 1. Epothilone D(EpoD) is a microtubules (MTs)-stabilizing agent 2.體內(nèi)研究 To evaluate whether

5、 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 3mg/kg) for a total of 3 months. In addition, 3-month old non-Tg littermates received 3 mg/kg Epothilone D(EpoD) or ve

6、hicle. The 3 mg/kg Epothilone D (EpoD) dose corresponds to 10-fold less than that used in aPhase 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

7、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)-treatedmice. The motor performance of Epothilone D (EpoD)-treated mice, assessed using a stan

8、dard rotarod test,is not significantly different from vehicle-treated cohorts. Finally, although there is minor group-to-groupvariability, there are no significant differences in white blood cell counts or neutrophil content between any ofthe treatment cohorts. Thus, the low doses of Epothilone D (E

9、poD) utilized in these studies appeared to bewell tolerated 2.PROTOCOLAnimal Mice 2Administration 2 Groups of mice (n=3) receive intraperitoneal (i.p.) injections of 3.7 mg/kg of Epothilone D (epoD) dissolved in100% DMSO, followed by euthanization using approved at times ranging from 0.25 h to 24 h.

10、 In anotherstudy, groups of mice (n=3) receive injections of 3 mg/kg of epoD in 100% DMSO followed by euthanization4, 6 and 10 days later. The Epothilone D (epoD) levels in brain and blood samples are determined using LC-MS/MS protocols. Groups (n=10-13) of 3-month old PS19 tau Tg mice or 3-month ol

11、d non-Tg littermates areadministered weekly i.p. injections of 1 mg/kg epoD, 3 mg/kg of Epothilone D (epoD) or vehicle (DMSO), fora total of 3 months. Animals are monitored for signs of abnormal behavior or distress, and are weighedweekly. After final dosing, the mice undergo motor function and cogn

12、itive testing. After euthanization, brainsand optic nerve (ON) are recovered for immunohistochemical analyses. A subset of mice from each groupalso undergo necropsy evaluation with organ weights recorded.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶

13、使本產(chǎn)品發(fā)表的科研獻(xiàn) Chemical Biology. Harvard University. 2019 May.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Konner J, et al. Phase I clinical, pharmacokinetic, and pharmacodynamic study of KOS-862 (Epothilone D) in patients with advanced2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEsolid tumors and lymphoma. Invest New Drugs. 2012 Dec;30(6):2294-302.2. Brunden KR, et al. Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy.J Neurosci. 2010 Oct 13;30(41):13