利伐沙班作用機制 - Medchemexpress - MCE中國

1、Product Data SheetRivaroxabanCat. No.: HY-50903CAS No.: 366789-02-8分式: CHClNOS分量: 435.88作靶點: Factor Xa作通路: Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 50 mg/mL (114.71 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制備儲備液

2、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備液；旦配成溶液，請分裝保存，避免反復凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內使，-20C 儲存時，請在 1 個內使。體內實驗請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍浮Ｒ韵氯芙獍付颊埾劝凑?In Vitro 式配制澄清的儲備液，再依次添加助溶劑

3、：為保證實驗結果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當保存；體內實驗的作液，建議您現(xiàn)現(xiàn)配，當天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶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 ultrasonic此案可獲得 2.5 mg/mL (5.74 mM) 的均勻懸濁液，懸濁液可于服和腹腔注射。以 1 mL 作液為例，取 100 L

4、 25.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.74 mM); Clear solution此案可獲得 2.5 mg/mL (5.74 mM，飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。Page 1 of 2 www.MedChemE以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加

5、到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Rivaroxaban種效，選擇性直接的凝因 Xa (FXa) 抑制劑，IC50 為 0.7 nM，Ki 為 0.4 nM。IC & 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 throm

6、bosis. Rivaroxaban competitively inhibits human FXa (Ki 0.4 nM) with 10 000-fold greater selectivity than for other serine proteases; it also inhibits prothrombinase activity (IC50 2.1 nM).Rivaroxaban inhibits endogenous FXa more potently in human and rabbit plasma (IC50 21 nM) than rat plasma (IC50

7、290 nM). It demonstrates anticoagulant effects in human plasma, doubling prothrombin time (PT) and activatespartial thromboplastin time at 0.23 and 0.69 M, respectively2.體內研究 Rivaroxaban (BAY 59-7939) is a potent and selective, direct FXa inhibitor with excellent in vivo activity and good oralbioava

8、ilability1. Rivaroxaban (BAY 59-7939), administered by i.v. bolus before thrombus induction, reduces thrombusformation (ED50 0.1 mg/kg), inhibits FXa, and prolongs PT dose dependently. PT and FXa are affected slightly at theED50 (1.8-fold increase and 32% inhibition, respectively). At 0.3 mg/kg (dos

9、e leading to almost complete inhibition ofthrombus formation), Rivaroxaban moderately prolongs PT (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 chromogenic orfluorogenic substrates

10、in 96-well microtiter plates at 25C. The enzymes are incubated with Rivaroxaban or itssolvent, DMSO, for 10 min. The reactions are initiated by the addition of the substrate, and the color or fluorescenceis monitored continuously at 405 nm using a Spectra Rainbow Thermo Reader, or at 630/465 nm usin

11、g aSPECTRAfluor plus, respectively, for 20 min. Enzymatic activity is analyzed in the following buffers (finalconcentrations): human FXa (0.5 nM), rabbit FXa (2 nM), rat FXa (10 nM), or urokinase (4 nM) in 50 mM Tris-HClbuffer, pH 8.3, 150 mM NaCl, and 0.1% bovine serum albumin (BSA); Pefachrome FXa

12、 (50-800 M) or chromozym U(250 M) with thrombin (0.69 nM), trypsin (2.2 nM), or plasmin (3.2 nM) in 0.1 M Tris-HCl, pH 8.0, and 20 mM CaCl2;chromozym TH (200 M), chromozym plasmin (500 M), or chromozymtrypsin (500 M) with FXIa (1 nM) or APC (10nM) in 50mM phosphate buffer, pH 7.4, 150 mM NaCl; and S

13、 2366 (150 or 500 M) with FVIIa (1 nM) and tissuefactor (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-benzylsulfon-amide H2O (100 M) and measured for 3 h. The FIXab/FX assay, comprising FIXab (8.8nM) and FX (9.5 nM) in 50 mM Tris

14、-HCl buffer, pH 7.4, 100 mM NaCl, 5 mM CaCl2 and 0.1% BSA, is started by theaddition of 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 the Michae

15、lis-Menten constant. Km is determined from a Lineweaver-Burk plot. The IC50 is the amount of inhibitor required todiminish the initial velocity of the control by 50%2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats2Administration 2 Fasted, m

16、ale 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 and twoloose sutures (8-10 mm apart) are placed below the left renal venous branch. Rivaroxaban dissolve

17、d in polyethylenePage 2 of 3 www.MedChemEglycol/H2O/glycerol (996 g/100 g/60 g), or vehicle is given by intravenous (i.v.) bolus injection into a tail vein 15 minbefore thrombus induction. Thromboplastin (0.5 mg/kg) is injected into a femoral vein and, after 15 s, the proximaland distal sutures are

18、tied. Fifteen minutes later, the ligated segment is removed, the thrombus withdrawn andweighed. Blood samples are obtained by cardiac puncture immediately before thrombus removal.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Pharmaceutics. 2019 Mar 19;11(3). pii: E133. Thromb Res. 2016 Jul;143:28-33. J Pharm Sci. 2017 Sep;106(9):2524-2534. Int J Lab Hematol. 2019 Nov 22. Patent. US20170224812A1.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Roehrig S, et al. Discover