考布他丁 A4作用机制 - Medchemexpress - MCE中国

1、Product Data SheetCombretastatin A4Cat. No.: HY-N2146CAS No.: 117048-59-6分式: CHO分量: 316.35作靶点: Microtubule/Tubulin作通路: Cell Cycle/DNA Damage; Cytoskeleton储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (316.11 mM; Need ultrasonic)H2O : 0.1 mg/mL (inso

2、luble)SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 3.1611 mL 15.8053 mL 31.6106 mL5 mM 0.6322 mL 3.1611 mL 6.3221 mL10 mM 0.3161 mL 1.5805 mL 3.1611 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：-80C, 6 months; -20C, 1 month。-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

3、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% Tween-80 45% salineSolubility: 3 mg/mL (9.48 mM); Clear solution此案可获得 3 mg/mL (9.48 mM，饱和度未知) 的澄清溶液。以

4、 1 mL 作液为例，取 100 L 30.0 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% corn oilSolubility: 3 mg/mL (9.48 mM); Clear solutionPage 1 of 2 www.MedChemE此案可获得 3 mg/mL (9.48 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，取 100 L 30.0 mg/m

5、L 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Combretastatin A4种 microtubule 抑制剂，能够与 -tubulin 结合，Kd 值为 0.4 M。IC & Target Kd: 0.4 M (-tubulin)体外研究 Combretastatin A4 phosphate ( 50 M) significantly increases the percentage of annexin-V-binding cells andsignificantly decreases forward scatter. C

6、ombretastatin A4 phosphate does not appreciably increase hemolysis.Hundred M Combretastatin A4 phosphate significantly increases Fluo3-fluorescence. The effect of CombretastatinA4 phosphate (100 M) on annexin-V-binding is significantly blunted, but not abolished, by removal of extracellularCa2+. Com

7、bretastatin A4 phosphate ( 50 M) significantly decreases GSH abundance and ATP levels but does notsignificantly increase ROS or ceramide2. Polymersomes co-encapsulating doxorubicin-combretastatin-A4 phosphate(1:10) shows strong synergistic cytotoxicity against human nasopharyngeal epidermal carcinom

8、a (KB) cells3.Pretreatment with Combretastatin A4 phosphate does not influence the amount of VM in 3-D culture as well as theexpression of these key molecules4.体内研究 DBP and MBP at 30 minutes after administration are higher in rats treated with Combretastatin A4 disodiumphosphate 120 mg/10 mL/kg. The

9、 toxicokinetic parameters of Combretastatin A4 phosphate and Combretastatin A4in rats treated with Combretastatin A4 disodium phosphate 120 mg/10 mL/kg are indicated, and the values of Cmax,T1/2, and AUC0-inf for Combretastatin A4 are 15613 M, 5.871.69 h, and 89.410.1 hM, respectively1. In vivo,W256

10、 tumors show marked intratumoral hypoxia after Combretastatin A4 phosphate treatment, accompanied byincreased VM formation. Combretastatin A4 phosphate exhibits only a delay in tumor growth within 2 days but rapidtumor regrowth afterward. VM density is positively related to tumor volume and tumor we

11、ight at day 8.Combretastatin A4 phosphate causes hypoxia which induces VM formation in W256 tumors through HIF-1/EphA2/PI3K/matrix metalloproteinase (MMP) signaling pathway, resulting in the consequent regrowth of thedamaged tumor4.PROTOCOLAnimal Rats: Rats are administered a single intravenous dose

12、 of Combretastatin A4 disodium phosphate at 120 mg/10 mL/kgAdministration 1 by bolus infusion (n=3). Blood is taken via the jugular vein and collected in heparin-coated tubes at 10 minutes and1, 3, 6, and 24 hours after administration. Plasma is separated by centrifugation immediately after sampling

13、. Aftercentrifugation, an aliquot of plasma is mixed with the equivalent volume of 1% formic acid and stored at 20C. Thethawed plasma samples are purified by solid-phase extraction, and the plasma concentrations of combretastatin A4phosphate (free base of Combretastatin A4 disodium phosphate; Combre

14、tastatin A4 phosphate) and combretastatinA4 (the metabolite of Combretastatin A4 disodium phosphate; Combretastatin A4 ) are determined by liquidchromatography-tandem mass spectrometry (LC-MS/MS). Toxicokinetic parameters maximum concentration (Cmax),terminal half-life (T1/2), and area under the con

15、centration-time curve from time zero to infinity (AUC0-inf) areobtained by non-compartmental analysis using Phoenix WinNonlin 6.3.MCE 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Page 2 of 3 www.MedChemE ACS Appl Mater Interfaces. 2018 Jun 6;1

16、0(22):18560-18573.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Tochinai R, et al. Combretastatin A4 disodium phosphate-induced myocardial injury. J Toxicol Pathol. 2016 Jul;29(3):163-71.2. Signoretto E, et al. Stimulation of Eryptosis by Combretastatin A4 Phosphat

17、e Disodium (CA4P). Cell Physiol Biochem. 2016;38(3):969-813. Zhu J, et al. Co-Encapsulation of Combretastatin-A4 Phosphate and Doxorubicin in Polymersomes for Synergistic Therapy of Nasopharyngeal EpidermalCarcinoma. J Biomed Nanotechnol. 2015 Jun;11(6):997-1006.4. Yao N, et al. Combretastatin A4 phosphate treatment induces vasculogenic mimicry formation of W256 breast carcinoma tumor in vitro and in vi