唑喹达三盐酸盐作用机制 - Medchemexpress - MCE中国

1、Product Data SheetZosuquidar trihydrochlorideCat. No.: HY-50671CAS No.: 167465-36-3分式: CHClFNO分量: 636.99作靶点: P-glycoprotein作通路: Membrane Transporter/Ion Channel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 H2O : 5 mg/mL (7.85 mM; Need ultrasonic)DMSO : 1 mg/mL (1.57

2、 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制备储备液1 mM 1.5699 mL 7.8494 mL 15.6988 mL5 mM 0.3140 mL 1.5699 mL 3.1398 mL10 mM 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 1. Zosuquidar is dissolv

3、ed in 20% ethanol-saline5.BIOLOGICAL ACTIVITY物活性 Zosuquidar trihydrochlorideP-糖蛋的抑制剂， Ki值为59 nM。IC & Target Ki: 59nM (P-glycoprotein)1.体外研究 Zosuquidar completely or partially restores drug sensitivity in all P-gp-expressing leukemia cell lines and enhancesthe cytotoxicity of anthracyclines (daunorub

4、icin, idarubicin, mitoxantrone) and gemtuzumab ozogamicin (Mylotarg) inprimary AmL blasts with active P-gp. In addition, P-gp inhibition by zosuquidar is found to be more potent thancyclosporine A in cells with highly active P-gp2.Page 1 of 2 www.MedChemE体内研究 Zosuquidar trihydrochloride is only mode

5、rately active as an inhibitor of P-gp at the blood-brain. An oral dose of 25mg/kg of zosuquidar trihydrochloride increases the brain concentrations by about 2.5-fold at 1 h and 5-fold at 24 h after paclitaxel administrationbarrier3. Zosuquidar enhances the brain uptake of nelfinavir in a dose-depend

6、entmanner. Brain tissue/plasma nelfinavir concentration ratios increase from 0.060.03 in the absence of zosuquidaradministration and 0.090.02 between 2 and 6 h after a 2 mg/kg intravenous dose of zosuquidar to 0.850.19 after6h and 1.580.67 after 20 mg/kg zosuquidar4.PROTOCOLCell Assay 2 Cells are cu

7、ltured in 96-well plates. Each drug of interest is added at escalating concentrations in the presence orabsence of either zosuquidar or CsA. After 48 hour incubation (except Mylotarg, 4 days incubation), 20 L of MTT isadded to each well for a further 4 hour incubation. The purple precipitate is diss

8、olved in 200 L DMSO, and the opticdensity (OD) is determined by the multi-well plate reader2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats: Female Sprague-Dawley rats are used in the study. Zosuquidar solutions are prepared in 5% mannitol

9、andAdministration 34adjusted to pH 2.0 with concentrated HCl. Nelfinavir is infused (10 mg/kg/h) for up to 10 h with or withoutconcurrent administration of an intravenous bolus dose of 2, 6, or 20 mg/kg zosuquidar given at 4 h. Brain tissueand plasma are analyzed for both drug concentrations4.Mice:

10、A stock solution of 5 mg/mL of zosuquidar trihydrochloride is prepared in vehicle solution and diluted in sterilesaline. The vehicle solution consisted of 20 g/l mannitol and 1.5 g/l of glycine in water for injection and adjusted to apH of 2.7 with hydrochloric acid. P-gp knockout mice and wild type

11、 mice are used as a model for complete inhibitionof P-gp. Zosuquidar trihydrochloride is administered orally at 25 and 80 mg/kg 1 h before i.v. paclitaxel and i.v. at 20mg/kg 10 min and 1 h before paclitaxel. The concentrations of paclitaxel in plasma and tissues and of zosuquidartrihydrochloride in

12、 plasma are quantified by high-performance liquid chromatography3.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 Cancer Cell. 2017 Apr 10;31(4):501-515.e8. Drug Metab Dispos. 2017 May;45(5):449-456. J Pharm Biomed Anal. 2012 Jul;66:232-9. J

13、 Chromatogr B Analyt Technol Biomed Life Sci. 2018 May 31;1092:72-81. Biomed Res Int. 2014;2014:850493.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Cripe LD, et al. Zosuquidar, a novel modulator of P-glycoprotein, does not improve the outcome of older patients wit

14、h newly diagnosed acute myeloidleukemia: a randomized, placebo-controlled trial of the Eastern Cooperative Oncology Group 3999. Blood.?2012. Tang R, et al. Zosuquidar?restores drug sensitivity in P-glycoprotein expressing acute myeloid leukemia (AmL). BMC Cancer.?2008 Feb 13;8:51.?3. Kemper EM, et a

15、l. The influence of the P-glycoprotein inhibitor zosuquidar trihydrochloride (LY335979) on the brain penetration of paclitaxel in mice.Cancer Chemother Pharmacol. 2004 Feb;53(2):173-8.Page 2 of 3 www.MedChemE4. Anderson BD, et al. Dependence of nelfinavir brain uptake on dose and tissue concentratio

16、ns of the selective P-glycoprotein inhibitor zosuquidar in rats.Drug Metab Dispos. 2006 Apr;34(4):653-9.5. Hou J, et al. Quantitative determination and pharmacokinetic study of the novel anti-Parkinsons disease candidate drug FLZ in rat brain by highperformance liquid chromatography-tandem mass spectrometry. J Pharm Biomed Ana