| 名稱 | Rivaroxaban |
| 描述 | Rivaroxaban (BAY 59-7939) is an orally bioavailable oxazolidinone derivative and direct inhibitor of the coagulation factor Xa with anticoagulant activity. Upon oral administration, rivaroxaban selectively binds to both free factor Xa and factor Xa bound in the prothrombinase complex. This interferes with the conversion of prothrombin (factor II) to thrombin and eventually prevents the formation of cross-linked fibrin clots. Rivaroxaban does not affect existing thrombin levels. |
| 細(xì)胞實(shí)驗(yàn) | LLC-PK1 and L-MDR1 cells are seeded in 96-well culture plates with microporous polycarbonate inserts and grown for 4 days in the same medium as used for cell cultures but without vincristine. The medium is replaced every 2 days. Before running the assay, the culture medium is replaced by HBSS buffer supplemented with 10 mM HEPES. Rivaroxaban are dissolved in DMSO and diluted with transport buffer to the respective final test concentrations (final DMSO concentration is always 1%). For inhibitor studies, the inhibitor is added at the appropriate concentration. counted. After 2 hour incubation at 37 °C, samples are taken from both compartments and, after the addition of ammonium acetate buffer and acetonitrile, are analyzed by LC-MS/M (Only for Reference) |
| 激酶實(shí)驗(yàn) | Factor Xa Activity : The activity of Rivaroxaban against purified serine proteases is measured using chromogenic or fluorogenic substrates in 96-well microtiter plates. The enzymes are incubated with Rivaroxaban or its solvent, dimethyl sulfoxide (DMSO), for 10 minutes. The reactions are initiated by the addition of the substrate, and the color or fluorescence is monitored continuously at 405 nm using a Spectra Rainbow Thermo Reader, or at 630/465 nm using a SPECTRAfluor plus, respectively, for 20 minutes. Enzymatic activity is analyzed in the following buffers (final concentrations): human FXa (0.5 nM), rabbit FXa (2 nM), rat FXa (10 nM), or urokinase (4 nM) in 50 mM Tris–HCl buffer pH 8.3, 150 mM NaCl, and 0.1% bovine serum albumin (BSA); Pefachrome FXa (50–800 μM) or chromozym U (250 μM) with thrombin (0.69 nM), trypsin (2.2 nM), or plasmin (3.2 nM) in 0.1 μM Tris–HCl, pH 8.0, and 20 mM CaCl2; chromozym TH (200 μM), chromozym plasmin (500 μM), or chromozym trypsin (500 μM) with FXIa (1 nM) or APC (10 nM) in 50 mM phosphate buffer, pH 7.4, 150 mM NaCl; and S 2366 (150 or 500 μM) with FVIIa (1 nM) and tissue factor (3 nM) in 50 mM Tris–HCl buffer,pH 8.0, 100 mM NaCl, 5 mM CaCl2 and 0.3% BSA, H-D-Phe-Pro-Arg-6-amino-1-naphthalene-benzylsulfonamide-Water (100 μM) and measured for 3 hours. The FIXaβ/FX assay, comprising FIXaβ (8.8 nM) and FX (9.5 nM) in 50 mM Tris–HCl buffer, pH 7.4, 100 mM NaCl, 5 mM CaCl2 and 0.1% BSA, is started by the addition of I-1100 (50 μM), and measured for 60 minutes. The inhibitory constant (Ki) against FXa is calculated according to the Cheng–Prusoff equation. The IC50 is the amount of inhibitor required to diminish the initial velocity of the control by 50%. |
| 體外活性 | 在大鼠和兔的動靜脈分流模型中,口服Rivaroxaban可減少動脈血栓形成（ED50：5.0 mg/kg和0.6 mg/kg）.在大鼠靜脈瘀血模型實(shí)驗(yàn)中,靜脈注射Rivaroxaban可劑量依賴地減少靜脈血栓形成（ED50：0.1 mg/kg）.在狗0.3-3 mg/kg ,大鼠1-10 mg/kg的研究劑量范圍內(nèi),Rivaroxaban血漿藥代動力學(xué)呈線性.Rivaroxaban的血漿清除率較低: 狗 0.3 L/(kg·h) ,大鼠0.4 L/(kg·h) ;分布體積(V(ss))穩(wěn)定: 狗0.4 L/kg,大鼠0.3 L/kg.Rivaroxaban在兩種物種中口服的消除半衰期都比較短 (0.9-2.3 h). |
| 體內(nèi)活性 | Rivaroxaban是一種直接抑制活化X因子口服抑制劑（Ki：0.4 nM）,同時對凝血酶原酶活性也有抑制作用（IC50：2.1 nM）,用于動靜脈血栓生成的預(yù)防和治療。對于純化的人源和兔源FXa,Rivaroxaban親和性類似（IC50：0.7 nM和0.8 nM）, 但對于大鼠FXa親和性較差（IC50：3.4 nM）。在血漿中, Rivaroxaban對人和兔內(nèi)源FXa抑制效果相當(dāng)（IC50：21 nM）,但在大鼠血漿中的抑制效果較差（IC50：290 nM）。在Caco-2細(xì)胞中,Rivaroxaban是具有極化運(yùn)輸特性和高滲透性的P-gp底物, 在體外實(shí)驗(yàn)中,即使到100 μM仍然不影響P-gp介導(dǎo)的藥物運(yùn)輸。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 81 mg/mL (185.8 mM)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | Fxa | Inhibitor | Factor Xa | Rivaroxaban | inhibit |
| 相關(guān)產(chǎn)品 | Dabigatran Etexilate Mesylate | Heparin sodium salt | 2-Methoxyphenothiazine | Coumarin | Thrombin (MW 37kDa) | (S)-(+)-Ibuprofen | Menadione | Ozagrel | AEBSF hydrochloride |
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