Apixaban-BMS-562247-01-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEApixabanCat. No.: HY-50667CAS No.: 503612-47-3Synonyms: BMS-562247-01分式: CHNO分量: 459.5作靶点: Factor Xa作通路: Metabolic Enzyme/Protease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 : 14.25 mg/mL

2、 (31.01 mM; Need ultrasonic and warming)H2O : 95% pure as judged by sodium dodecylsulfate polyacrylamide gel electrophoresis. Thesubstrate affinity values for FXa, expressed as the Michaelis-Menten-Henri constant (Km), for human, rabbit,rat and dog FXa are determined using the chromogenic substrate

3、S-2765, and are 36, 60, 240 and 70 M,respectively. The substrate hydrolysis is monitored by measuring absorbance at 405 nm at 25C for up to 30min using a SpectraMax 384 Plus plate reader and SoftMax. FXa activity for each substrate and inhibitorconcentration pair is determined in duplicate. The Ki v

4、alues are calculated by non-linear least-squares fittingof the steady-state substrate hydrolysis rates to the equation for competitive inhibition (Equation 1) usingGRAFIT, where v equals reactions velocity in OD min1, Vmax equals maxiumum reaction velocity, S equalssubstrate concentration, and I equ

5、als inhibitor concentration.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Briefly, male New Zealand White rabbits are anesthetized with ketamine (50 mg/kg i.m.) and xylazine (10Administration 2 mg/kg i.m.), and their femoral artery, jugular vei

6、n and femoral vein are catheterized. These anesthetics aresupplemented as needed. Thrombosis is induced by an arteriovenous (AV)-shunt device containing a silkthread. Blood flowed from the femoral artery via the AV shunt into the opposite femoral vein for 40 min. Theshunt is then disconnected and th

7、e silk thread covered with thrombus is weighed. As apixaban has an oralbioavailability of 5% in rabbits (unpublished result), it is administered intravenously for in vivo studies. Toachieve a stable plasma level with minimum experimental variability, apixaban, fondaparinux or vehicle isgiven by a co

8、ntinuous intravenous infusion 1 h prior to shunt placement. The infusion is continued throughoutthe experiment. Warfarin or vehicle is dosed orally once daily for 4 days. On the fourth day after the last oraldose of warfarin or vehicle, rabbits are anesthetized 1.5 h later, and the treatment effect

9、is evaluated about 2h postdose. Arterial blood samples for the determination of clotting times or plasma levels are collected 20min after shunt placement. Plasma levels of apixaban are measured by a specific and sensitive liquidchromatographic mass spectrometry method (LC/MS/MS). In rabbits treated

10、with apixaban, fondaparinux or2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEwarfarin, the antithrombotic effects of these agents are expressed as percentage inhibition of thrombusformation based on the treated vs. the corresponding mean vehicle. The ED50 value (dose that produced50% inhibition of

11、 thrombus formation) is determined as described below. The apixaban group treatmentconsists of vehicle (10%N,N-dimethylacetamide; 30% 1,2-propanediol; 60% water) (n=4), and apixaban(mg/kg/h) at 0.03 (n=7), 0.1 (n=7), 0.3 (n=7), 1 (n=7), and 3 (n=3). The fondaparinux group treatmentconsists of vehicl

12、e (saline) (n=6), and fondaparinux (mg/kg/h1) at 0.01 (n=5), 0.03 (n=5), 0.1 (n=5), 0.3 (n=5),and 1 (n=5). The warfarin group treatment consists of vehicle (water) (n=6), and warfarin (mg/kg/day) at 0.1(n=6), 0.3 (n=6), 1 (n=6), and 3 (n=6).MCE has not independently confirmed the accuracy of these m

13、ethods. They are for reference only.户使本产品发表的科研献 J Thromb Haemost. 2013 Dec;11(12):2118-27. Personalized Medicine Universe. 2019 May. Patent. US20170224812A1.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Pinto DJ, et al. Discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperi

14、din-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo3,4-cpyridine-3-carboxamide (apixaban, BMS-562247), a highly potent, selective, efficacious, and orally bioavailable inhibitor of blo2. Wong PC, et al. Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and anti

15、hemostatic studies. JThromb Haemost. 2008 May;6(5):820-9.3. Zhang D, et al. Metabolism, pharmacokinetics and pharmacodynamics of the factor Xa inhibitor apixaban in rabbits. J ThrombThrombolysis. 2010 Jan;29(1):70-80.4. He K, et al. Preclinical pharmacokinetics and pharmacodynamics of apixaban, a potent and selective factor Xa inhibitor. Eur J DrugMetab Pharmacok