多西他赛作用机制 - Medchemexpress - MCE中国

1、Product Data SheetDocetaxelCat. No.: HY-B0011CAS No.: 114977-28-5分式: CHNO分量: 807.88作靶点: Microtubule/Tubulin; Apoptosis; Endogenous Metabolite作通路: Cell Cycle/DNA Damage; Cytoskeleton; Apoptosis; Metabolic Enzyme/Protease储存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect

2、from light)溶解性数据体外实验 DMSO : 35 mg/mL (43.32 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 1.2378 mL 6.1890 mL 12.3781 mL5 mM 0.2476 mL 1.2378 mL 2.4756 mL10 mM 0.1238 mL 0.6189 mL 1.2378 mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：

3、-80C, 6 months; -20C, 1 month (protect from light)。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5%

4、Tween-80 45% salineSolubility: 2.5 mg/mL (3.09 mM); Clear solution此案可获得 2.5 mg/mL (3.09 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (3.09 mM); C

5、lear solution此案可获得 2.5 mg/mL (3.09 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合Page 1 of 2 www.MedChemE均匀。3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (3.09 mM); Clear solution此案可获得 2.5 mg/mL (3.09 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例

6、，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Docetaxel (RP-56976)种抗肿瘤试剂，抑制微管解聚 (microtubule depolymerization) 的 IC50 值为 0.2 M。Docetaxel (RP-56976)是紫杉醇的半合成类似物，能减弱 bcl-2 和 bcl-xL基因表达的影响。Docetaxel (RP-56976) 阻滞G2/M 细胞周 期，导致细胞凋亡 (apoptosis)。IC & Target Human Endogenous Metaboli

7、te(批量添加)体外研究 Docetaxel (RP-56976) and Glufosfamide (GLU) single and combined treatments affect the cells viability in a dose-dependent manner. The IC50 of GLU are 704 M and 86.88 M in PC-3 and LNCaP cells; respectively. While, the IC50 of Docetaxel alone is found to be 3.080.4 nM and 1.460.2 nM in P

8、C-3 and LNCaP cells; respectively.The co-treatment of GLU with Docetaxel is found to synergize the cytotoxicity and the IC50 values are decreased to be2.70.1 nM and 0.750.3 nM in PC-3 and LNCaP cells; respectively1.IC50 of NCI-H460 to Docetaxel at 24 h is 116 nM and at 72 h is 30 nM. According to da

9、ta reported in DTP DataSearch, the mean IC50 of NCI-60 cell panel to Docetaxel is 14-34 nM2.体内研究 In female mice, the Docetaxel (RP-56976)-induced intestinal apoptosis in the 14-hours after light on (HALO) group issignificantly greater than that in the 2-HALO group. Bax expression is significantly el

10、evated by Docetaxel in the 2-HALO group, but not in the 14-HALO group. On the other hand, cleaved Caspase-3 expression is significantlyelevated by Docetaxel in the 14-HALO group, but not in the 2-HALO group. The expressions of Wee1 andphosphorylated CKD1 are significantly elevated after dosing of Do

11、cetaxel at 14 HALO, but not at 2 HALO. In addition,Docetaxel significantly reduces survivin expression in the 14-HALO group but not in the 2-HALO group. The survivinexpression level in the Docetaxel-treated 14-HALO group is significantly smaller than that in the drug-treated 2-HALOgroup3.Piperine (P

12、IP) is administrated via intravenous bolus at 3.5 mg/kg and via oral administration at 35 mg/kg and 3.5mg/kg, while Docetaxel (DOX) is intravenously administrated at 7 mg/kg to Sprague-Daley rats. The co-administrations of PIP at 35 mg/kg via oral administration and Docetaxel at 7 mg/kg via intraven

13、ous bolusadministration in Sprague-Dawley rats. The combination use of PIP and Docetaxel results in a synergic increase ofboth their in vivo exposure4.PROTOCOLCell Assay 1 Single-drug concentration-response curves are assessed. Seeding is done at a density of 2,000 cells/well for PC-3 andLNCaP, in 9

14、6-well plates. Cells are treated with each single drug and their combination for 72 h at different drugconcentrations. Docetaxel is used at concentrations of 0.1-1,000 nM. GLU is used at concentrations of 0.1-300 m.Cytotoxicity is assessed at the end of drug exposure using SRB assay. Following 72 h

15、exposure the cells are fixed with10% trichloroacetic acid (150 L) for 1 h at 4C. Then, cells are stained for 10 min at room temperature with 0.4% SRBdissolved in 1% acetic acid. The plates are then air dried for 24 h and the dye is made soluble with 150 L Tris (10mM, PH 7.4) for 5 min on a shaker at

16、 1,600 rpm. Absorbance is then measured at 545 nM using microplate reader.Results are expressed as the relative percentage of absorbance compared to control1.Page 2 of 3 www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice3Administrat

17、ion 34 Five-week-old male Balb/c mice are used. Docetaxel (0, 10, 20, 30, 40, 60, and 80 mg/kg per week) is given once aweek for 3 weeks for mice. Because more than 30 mg/kg per week of Docetaxel causes body weight loss in mice, 20mg/kg per week of Docetaxel is judged to be the maximum nontoxic dose

18、. Docetaxel (20 mg/kg per week) is givento mice once a week for 3 weeks at one of the following different points (2, 10, 14, or 22 HALO). Seventy-two hoursafter the final dosing of the agent, the intestinal mucosa of the small intestine (proximal 8 cm) is removed, fixed in 20N Mildform solution (con

19、taining 8% formaldehyde in a buffered solution), and embedded in paraffin blocks, andsections of 5 m are put on glass slides. Apoptosis is detected using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method, using the Apop Tag Peroxidase In Situ Apoptosis Detectio

20、n Kit.Rats4Male Sprague-Dawley rats with body weight between 230-250 g and age between 6-7 weeks are used. About 25 SDrats are divided into five groups receiving Docetaxel (7 mg/kg, i.v.), PIP (35 mg/kg, p.o.) and their combinedadministration (DOX+PIP) as well as PIP (3.5 mg/kg, p.o.) and PIP (3.5 m

21、g/kg, i.v.). A day before the drugadministrations, the rats are anesthetized with an intramuscular injection of a cocktail containing 60 mg/kg ketamineand 6 mg/kg xylazine (injection volume, 0.2 mL). Right jugular vein is cannulated with a polyethylene tubing (0.5 mmID, 1 mm) for blood collection.MC

22、E has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Eur J Med Chem. 2018 Feb 25;146:157-170. Biochem Pharmacol. 2020 Mar 3:113865. Int J Mol Sci. 2019 Jan; 20(1): 28. Materials (Basel). 2020 Mar 2;13(5). pii: E1099. J Liposome Res. 2019 May 6:1-48.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Attia RT, et al. The chemomodulatory effects of glufosfamide on docetaxel cytotoxicity in prostate cancer cells. PeerJ. 2016 Jun 29