Docetaxel-RP-56976-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEDocetaxelCat. No.: HY-B0011CAS No.: 114977-28-5Synonyms: RP-56976分式: CHNO分量: 807.88作靶点: Microtubule/Tubulin作通路: Cell Cycle/DNA Damage; Cytoskeleton储存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect

2、fromlight)溶解性数据体外实验 DMSO : 35 mg/mL (43.32 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration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，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适

3、当的溶解案，配制前请先配制澄的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (3.09 mM); Clear solution2. 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); Clear solu

4、tion3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (3.09 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Docetaxel种抗肿瘤药，主 作机制抑制微管 (microtubule) 解聚，以及减弱 Bcl-2 和 Bcl-xL因表达的作。IC50 & Target Microtubule 1体外研究 Docetaxel (DOC) and Glufosfamide (GLU) sing

5、le 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 PC-3 and LNCaP cells;respectively. The co-treatment of GLU with

6、 Docetaxel is found to synergize the cytotoxicity and the IC50values are decreased to be 2.70.1 nM and 0.750.3 nM in PC-3 and LNCaP cells; respectively 1. IC50 ofNCI-H460 to Docetaxel at 24 h is 116 nM and at 72 h is 30 nM. According to data reported in DTP DataSearch, the mean IC50 of NCI-60 cell p

7、anel to Docetaxel is 14-34 nM 2.体内研究 In female mice, the Docetaxel-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 elevated by Docetaxel inthe 2-HALO group, but not in the 14-HALO group. O

8、n the other hand, cleaved Caspase-3 expression issignificantly elevated by Docetaxel in the 14-HALO group, but not in the 2-HALO group. The expressions ofWee1 and phosphorylated CKD1 are significantly elevated after dosing of Docetaxel at 14 HALO, but not at 2HALO. In addition, Docetaxel significant

9、ly reduces survivin expression in the 14-HALO group but not in the 2-HALO group. The survivin expression level in the Docetaxel-treated 14-HALO group is significantly smallerthan that in the drug-treated 2-HALO group 3. Piperine (PIP) is administrated via intravenous bolus at 3.5mg/kg and via oral a

10、dministration at 35 mg/kg and 3.5 mg/kg, while Docetaxel (DOX) is intravenouslyadministrated at 7 mg/kg to Sprague-Daley rats. The co-administrations of PIP at 35 mg/kg via oraladministration and Docetaxel at 7 mg/kg via intravenous bolus administration in Sprague-Dawley rats. Thecombination use of

11、PIP and Docetaxel results in a synergic increase of both their in vivo exposure 4.PROTOCOLCell Assay 1 Single-drug concentration-response curves are assessed. Seeding is done at a density of 2,000 cells/well forPC-3 and LNCaP, in 96-well plates. Cells are treated with each single drug and their comb

12、ination for 72 h atdifferent drug concentrations. Docetaxel is used at concentrations of 0.1-1,000 nM. GLU is used atconcentrations of 0.1-300 m. Cytotoxicity is assessed at the end of drug exposure using SRB assay.Following 72 h exposure the cells are fixed with 10% trichloroacetic acid (150 L) for

13、 1 h at 4C. Then, cellsare stained for 10 min at room temperature with 0.4% SRB dissolved in 1% acetic acid. The plates are thenair dried for 24 h and the dye is made soluble with 150 L Tris (10 mM, PH 7.4) for 5 min on a shaker at1,600 rpm. Absorbance is then measured at 545 nM using microplate rea

14、der. Results are expressed as therelative percentage of absorbance compared to control 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEAnimal Mice 3Administration 34 Five-week-old male Balb/c mice are u

15、sed. Docetaxel (0, 10, 20, 30, 40, 60, and 80 mg/kg per week) is givenonce a week for 3 weeks for mice. Because more than 30 mg/kg per week of Docetaxel causes body weightloss in mice, 20 mg/kg per week of Docetaxel is judged to be the maximum nontoxic dose. Docetaxel (20mg/kg per week) is given to

16、mice once a week for 3 weeks at one of the following different points (2, 10, 14,or 22 HALO). Seventy-two hours after the final dosing of the agent, the intestinal mucosa of the smallintestine (proximal 8 cm) is removed, fixed in 20 N Mildform solution (containing 8% formaldehyde in abuffered soluti

17、on), and embedded in paraffin blocks, and sections of 5 m are put on glass slides. Apoptosisis detected using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)method, using the Apop Tag Peroxidase In Situ Apoptosis Detection Kit.Rats 4Male Sprague-Dawley rats with bod

18、y weight between 230-250 g and age between 6-7 weeks are used.About 25 SD rats are divided into five groups receiving Docetaxel (7 mg/kg, i.v.), PIP (35 mg/kg, p.o.) andtheir combined administration (DOX+PIP) as well as PIP (3.5 mg/kg, p.o.) and PIP (3.5 mg/kg, i.v.). A daybefore the drug administra

19、tions, the rats are anesthetized with an intramuscular injection of a cocktailcontaining 60 mg/kg ketamine and 6 mg/kg xylazine (injection volume, 0.2 mL). Right jugular vein iscannulated with a polyethylene tubing (0.5 mm ID, 1 mm) for blood collection.MCE has not independently confirmed the accura

20、cy 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. Int J Mol Sci. 2018 Dec 21;20(1). pii: E28. J Liposome Res. 2019 May 6:1-48. J Microencapsul. 2019 Aug. Int J Clin Exp Pathol. 2017;10(3):3033-3042.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Attia RT, et al. The chemomodulatory effects of glufosfamide on docetaxel cytotoxicity in prostate cancer cells. PeerJ. 2016 Jun29;4:e2168.2. Che CL, et al. DNA microarray revea