您好,欢迎来到化工原料网! [登录] [免费注册]
化工原料网
位置:首页 > 产品库 > Apixaban(BMS-56224701)
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
Apixaban(BMS-56224701)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Apixaban(BMS-56224701)图片
CAS NO:503612-47-3
规格:≥98%
包装与价格:
包装价格(元)
100mg电议
250mg电议
500mg电议
1g电议
2g电议
5g电议
10g电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)459.5
FormulaC25H25N5O4
CAS No.503612-47-3
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 18 mg/mL (39.2 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/mL
Synonyms

BMS56224701; BMS 56224701; BMS 562247-01; Apixaban, BMS-56224701; brand name: Eliquis

Chemical Name: 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5-dihydropyrazolo[5,4-c]pyridine-3-carboxamide

SMILES CodeO=C(C1=NN(C2=CC=C(OC)C=C2)C3=C1CCN(C4=CC=C(N5C(CCCC5)=O)C=C4)C3=O)N
实验参考方法
In Vitro

In vitro activity: Apixaban exhibits a high degree of potency, selectivity, and efficacy on Factor Xa with Ki of 0.08 nM and 0.17 nM for Human Factor Xa and Rabbit Factor Xa, respectively. In vitro, Apixaban prolongs the clotting times of normal human plasma with the concentrations (EC2x) of 3.6 μM, 0.37 μM, 7.4 μM, and 0.4 μM, which are required respectively to double the prothrombin time (PT), modified prothrombin time (mPT), activated partial thromboplastin time (APTT) and HepTest. Besides, Apixaban shows the highest potency in human and rabbit plasma, but less potency in rat and dog plasma in both the PT and APTT assays.


Kinase Assay: Purified FXa is obtained after activation with Russell’s viper venom followed by affinity chromatography. The resulting FXa is> 95% pure as judged by sodium dodecylsulfate polyacrylamide gel electrophoresis. The substrate 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 S-2765, and are 36, 60, 240 and 70 μM, respectively. The substrate hydrolysis is monitored by measuring absorbance at 405 nm at 25°C for up to 30 min using a SpectraMax 384 Plus plate reader and SoftMax. FXa activity for each substrate and inhibitor concentration pair is determined in duplicate. The Ki values are calculated by non-linear least-squares fitting of the steady-state substrate hydrolysis rates to the equation for competitive inhibition (Equation 1) using GRAFIT, where v equals reactions velocity in OD min–1, Vmax equals maxiumum reaction velocity, S equals substrate concentration, and I equals inhibitor concentration.


Cell Assay: Apixaban exhibits a high degree of potency, selectivity, and efficacy on Factor Xa with Ki of 0.08 nM and 0.17 nM for Human Factor Xa and Rabbit Factor Xa, respectively. In vitro, Apixaban prolongs the clotting times of normal human plasma with the concentrations (EC2x) of 3.6 μM, 0.37 μM, 7.4 μM, and 0.4 μM, which are required respectively to double the prothrombin time (PT), modified prothrombin time (mPT), activated partial thromboplastin time (APTT) and HepTest. Besides, Apixaban shows the highest potency in human and rabbit plasma, but less potency in rat and dog plasma in both the PT and APTT assays.

In VivoIn the dog, Apixaban shows the excellent pharmacokinetics with very low clearance (Cl: 0.02 L kg-1 h-1), and low volume of distribution (Vdss: 0.2 L kg-1). Besides, Apixaban also exhibits a moderate half-life (T1/2: 5.8 hours) and good oral bioavailability (F: 58%). In the arteriovenous-shunt thrombosis (AVST), venous thrombosis (VT) and electrically mediated carotid arterial thrombosis (ECAT) rabbit models, Apixaban produces dose-dependent antithrombotic effects with EC50 of 270 nM, 110 nM and 70 nM, respectively.Apixaban significantly inhibits factor Xa activity with IC50 of 0.22 μM in rabbit ex vivo. In chimpanzee, Apixaban also shows small volume of distribution (Vdss: 0.17 L kg-1), low systemic clearance (Cl: 0.018 L kg-1 h-1), and good oral bioavailability (F: 59%).
Animal modelArteriovenous-shunt thrombosis (AVST), venous thrombosis (VT) and electrically mediated carotid arterial thrombosis (ECAT) rabbit models
Formulation & DosageDssolved in 10% N,N-dimethylacetamide; 30% 1,2-propanediol; 60% water; ≤3 mg/kg/h; i.v. injection
ReferencesJ Med Chem. 2007 Nov 1;50(22):5339-56; J Thromb Haemost. 2008 May;6(5):820-9; J Thromb Thrombolysis. 2010 Jan;29(1):70-80.