Rivaroxaban

製品コードS3002 バッチS300202

印刷

化学情報

Chemical Structure Synonyms BAY 59-7939 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C19H18ClN3O5S
分子量 435.88 CAS No. 366789-02-8
Solubility (25°C)* 体外 DMSO 87 mg/mL (199.59 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
0.5% methylcellulose 0.2% Tween 80
5.0mg/ml Taking the 1 mL working solution as an example, take 5 mg of this product and add it to 1 ml of 0.5% methylcellulose+0.2% Tween 80 clear solution, and mix evenly to form a uniform suspension. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Rivaroxaban is a direct inhibitor of Factor Xa with Ki and IC50 of 0.4 nM and 0.7 nM in cell-free assays, respectively. It is selective for human factor Xa, for which it has >10 000-fold greater selectivity than for other biologically relevant serine proteases (IC50 >20 μM).
in vitro Rivaroxaban is an oral, direct inhibitor of Factor Xa (FXa), being developed for the prevention and treatment of arterial and venous thrombosis with a Ki of 0.4 nM. Rivaroxaban also inhibits prothrombinase activity with IC50 of 2.1 nM. Rivaroxaban also shows a similar affinity to purified human and rabbit FXa (IC50 0.7 nM and 0.8 nM, respectively), but a lesser potency against purified rat FXa (IC50 3.4 nM). Endogenous human and rabbit FXa in plasma is inhibited to a similar extent by Rivaroxaban (IC50 21 nM and 21 nM, respectively), while 14-fold higher concentrations are required in rat plasma (IC50 290 nM). [1] Rivaroxaban exhibits high permeability and polarized transport across Caco-2 cells as a substrate of the P-gp, but exhibits no inhibitory effect on P-gp-mediated drug transport up to concentrations of 100 μM in vitro. [2]
in vivo Rivaroxaban reduces venous thrombosis in a dose dependent manner (ED50 0.1 mg/kg i.v.) in a rat venous stasis model. Rivaroxaban reduces arterial thrombus formation in an arteriovenous (AV) shunt in rats (ED50 5.0 mg/kg p.o.) and rabbits (ED50 0.6 mg/kg p.o.). [1] Plasma pharmacokinetics of Rivaroxaban are linear across the investigated dose range (1-10 mg/kg in rats, 0.3-3 mg/kg in dogs). Plasma clearance is low: 0.4 L/kg/h in rats and 0.3 L/kg/h in dogs; the volume of distribution (V(ss)) is moderate: 0.3 L/kg in rats, and 0.4 L/kg in dogs. The elimination half-life after oral administration is short in both species (0.9-2.3 hours). [3]

プロトコル(参考用のみ)

キナーゼアッセイ 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 50mM 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-H2O (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%.
細胞アッセイ 細胞株 Caco-2, wild-type, and P-gp-overexpressing LLC-PK1
濃度 0 - 100 μM
反応時間 2 hours
実験の流れ

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
動物実験 動物モデル Fasted, male Wistar rats (HsdCpb:WU) and fasted, female New Zealand White rabbits (Esd:NZW).
投薬量 ≤0.3 mg/kg for i.v. and ≤3 mg/kg for p.o.
投与方法 Administered via i.v. or p.o.

カスタマーフィードバック

Data from [Data independently produced by , , Nature, 2018, 555(7698):673-677]

Data from [Data independently produced by , , Eur J Clin Pharmacol, 2016, 72(6):671-9 ]

Data from [Data independently produced by , , Br J Biomed Sci, 2016, 73(3):134-139.]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Rivaroxaban attenuates neutrophil maturation in the bone marrow niche [ Basic Res Cardiol, 2023, 118(1):31] PubMed: 37580509
OKL-1111, A modified cyclodextrin as a potential universal reversal agent for anticoagulants [ Thromb Res, 2023, 227:17-24] PubMed: 37207560
pKr-2 induces neurodegeneration via upregulation of microglial TLR4 in the hippocampus of AD brain [ Brain Behav Immun Health, 2023, 28:100593] PubMed: 36798617
CM-352 EFFICACY IN A MOUSE MODEL OF ANTICOAGULANT-ASSOCIATED INTRACRANIAL HAEMORRHAGE [ Thromb Haemost, 2022, 10.1055/a-1759-9962] PubMed: 35114692
Evaluation of Xa inhibitors as potential inhibitors of the SARS-CoV-2 Mpro protease [ PLoS One, 2022, 17(1):e0262482] PubMed: 35015795
In vitro reversal of direct factor Xa inhibitors: Direct comparison of andexanet alfa and prothrombin complex concentrates Cofact and Beriplex/Kcentra [ Res Pract Thromb Haemost, 2022, 6(5):e12775] PubMed: 35928523
Control of hippocampal prothrombin kringle-2 (pKr-2) expression reduces neurotoxic symptoms in five familial Alzheimer's disease mice [ Br J Pharmacol, 2021, 10.1111/bph.15681] PubMed: 34524687
Unveiling the complex effects of direct oral anticoagulants on dilute Russell's viper venom time assays [ J Thromb Haemost, 2020, 18(8):1866-1873] PubMed: 32294291
Unveiling the complex effects of direct oral anticoagulants on dilute Russell's viper venom time assays [ Journal of Thrombosis and Haemostasis, 2020, 1866-1873] PubMed: None
An engineered factor Va prevents bleeding induced by direct-acting oral anticoagulants by different mechanisms [ Blood Adv, 2020, 4(15):3716-3727] PubMed: 32777068

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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