Rivaroxaban-BAY-59-7939-DataSheet-生命科學(xué)試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemERivaroxabanCat. No.: HY-50903CAS No.: 366789-02-8Synonyms: BAY 59-7939分式: CHClNOS分量: 435.88作靶點(diǎn): Factor Xa作通路: Metabolic Enzyme/Protease儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/

2、mL (114.71 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.2942 mL 11.4710 mL 22.9421 mL5 mM 0.4588 mL 2.2942 mL 4.5884 mL10 mM 0.2294 mL 1.1471 mL 2.2942 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請注意儲(chǔ)備液的保存式和期限。體內(nèi)實(shí)驗(yàn) 請根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄清的?chǔ)備液，再依次添加助溶劑(為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)

3、現(xiàn)配，當(dāng)天使；澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.74 mM); Suspended solution; Need ultrasonic2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.74 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www

4、.MedChemEBIOLOGICAL ACTIVITY物活性 Rivaroxaban種效，選擇性 凝因Xa抑制劑，具有強(qiáng)效抗凝因Xa活性，IC50 為 0.7 nM，Ki 為0.4 nM。IC50 & Target IC50: 0.7 nM (FXa) 1Ki: 0.4 nM (FXa) 1體外研究 Rivaroxaban (BAY 59-7939) is an oral, direct Factor Xa (FXa) inhibitor in development for the prevention andtreatment of arterial and venous thrombo

5、sis. Rivaroxaban competitively inhibits human FXa (Ki 0.4 nM) with10 000-fold greater selectivity than for other serine proteases; it also inhibits prothrombinase activity (IC502.1 nM). Rivaroxaban inhibits endogenous FXa more potently in human and rabbit plasma (IC50 21 nM) thanrat plasma (IC50 290

6、 nM). It demonstrates anticoagulant effects in human plasma, doubling prothrombin time(PT) and activates partial thromboplastin time at 0.23 and 0.69 M, respectively 2.體內(nèi)研究 Rivaroxaban (BAY 59-7939) is a potent and selective, direct FXa inhibitor with excellent in vivo activity andgood oral bioavail

7、ability 1. Rivaroxaban (BAY 59-7939), administered by i.v. bolus before thrombusinduction, reduces thrombus formation (ED50 0.1 mg/kg), inhibits FXa, and prolongs PT dose dependently.PT and FXa are affected slightly at the ED50 (1.8-fold increase and 32% inhibition, respectively). At 0.3mg/kg (dose

8、leading to almost complete inhibition of thrombus formation), Rivaroxaban moderately prolongsPT (3.20.5-fold) and inhibits FXa activity (653%) 2.PROTOCOLKinase Assay 2 The activity of Rivaroxaban (BAY 59-7939) against purified serine proteases is measured using chromogenicor fluorogenic substrates i

9、n 96-well microtiter plates at 25C. The enzymes are incubated with Rivaroxabanor its solvent, DMSO, for 10 min. The reactions are initiated by the addition of the substrate, and the color orfluorescence is monitored continuously at 405 nm using a Spectra Rainbow Thermo Reader, or at 630/465nm using

10、a SPECTRAfluor plus, respectively, for 20 min. Enzymatic activity is analyzed in the followingbuffers (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(

11、50-800 M) or chromozym U (250 M) with thrombin (0.69 nM), trypsin (2.2 nM), or plasmin (3.2 nM) in 0.1M Tris-HCl, pH 8.0, and 20 mM CaCl2; chromozym TH (200 M), chromozym plasmin (500 M), orchromozymtrypsin (500 M) with FXIa (1 nM) or APC (10 nM) in 50mM phosphate buffer, pH 7.4, 150 mMNaCl; and S 2

12、366 (150 or 500 M) with FVIIa (1 nM) and tissue factor (3 nM) in 50 mM Tris-HCl buffer, pH8.0, 100 mM NaCl, 5 mM CaCl2 and 0.3% BSA, H-D-Phe-Pro-Arg-6-amino-1-naphthalene-benzylsulfon-amide H2O (100 M) and measured for 3 h. The FIXab/FX assay, comprising FIXab (8.8 nM) and FX (9.5nM) in 50 mM Tris-H

13、Cl buffer, pH 7.4, 100 mM NaCl, 5 mM CaCl2 and 0.1% BSA, is started by the additionof I-1100 (50 M), and measured for 60 min. The inhibitory constant (Ki) against FXa is calculated accordingto the Cheng-Prusoff equation (Ki=IC50/1+S/Km), where S is the substrate concentration, and Km is theMichaelis

14、-Menten constant. Km is determined from a Lineweaver-Burk plot. The IC50 is the amount ofinhibitor required to diminish the initial velocity of the control by 50% 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您邊的抑制劑師www

15、.MedChemEAnimal Rats 2Administration 2 Fasted, male Wistar rats (HsdCpb:WU) are used. Rat venous stasis model Thrombus formation is induced inanesthetized rats (n=10 per dose group), with minor modifications. The abdominal vena cava is exposed andtwo loose sutures (8-10 mm apart) are placed below th

16、e left renal venous branch. Rivaroxaban dissolved inpolyethylene glycol/H2O/glycerol (996 g/100 g/60 g), or vehicle is given by intravenous (i.v.) bolus injectioninto a tail vein 15 min before thrombus induction. Thromboplastin (0.5 mg/kg) is injected into a femoral veinand, after 15 s, the proximal

17、 and distal sutures are tied. Fifteen minutes later, the ligated segment isremoved, the thrombus withdrawn and weighed. Blood samples are obtained by cardiac punctureimmediately before thrombus removal.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本

18、產(chǎn)品發(fā)表的科研獻(xiàn) Pharmaceutics. 2019 Mar 19;11(3). pii: E133. Thromb Res. 2016 Jul;143:28-33. J Pharm Sci. 2017 Sep;106(9):2524-2534. Patent. US20170224812A1.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Roehrig S, et al. Discovery of the novel antithrombotic agent 5-chloro-N-(5S)-2-oxo-3- 4-(3-oxomorpholin-4-yl)phenyl-1,3-oxazolidin-5-ylmethyl)thiophene- 2-carboxamide (BAY 59-7939): an oral, direct factor Xa inhibitor. J Med Chem. 2005 Sep 22;48(19)2. Perzborn E, et al. In vitro and in vivo studies of the novel antithrombotic agent BA