利托那韋作用機制 - Medchemexpress - MCE中國

1、Product Data SheetRitonavirCat. No.: HY-90001CAS No.: 155213-67-5分式: CHNOS分量: 720.94作靶點: HIV Protease; HIV; Apoptosis作通路: Anti-infection; Metabolic Enzyme/Protease; Apoptosis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 : 25 mg/mL (34.68 mM; Need ultrasonic)H2O

2、 : 0.1 mg/mL (insoluble)SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 1.3871 mL 6.9354 mL 13.8708 mL5 mM 0.2774 mL 1.3871 mL 2.7742 mL10 mM 0.1387 mL 0.6935 mL 1.3871 mL請根據(jù)產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

3、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：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 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (3.47 mM); Suspended solution; Need ultrasonic此案可獲

4、得 2.5 mg/mL (3.47 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 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (3.47 mM); Clear solution; Need warmingPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (3.47 mM) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取

5、 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Ritonavir (ABT 538)于治療HIV感染和AIDS的 HIV蛋酶的抑制劑。體外研究 Ritonavir (ABT 538) is an inhibitor of CYP3A4 mediated testosterone 6-hydroxylation with mean Ki of 19 nM and alsoinhibits tolbutamide hydroxylation with IC50 of 4.2 M1. Ritonavir (A

6、BT 538) is found to be a potent inhibitor ofCYP3A-mediated biotransformations (nifedipine oxidation with IC50 of 0.07 mM, 17alpha-ethynylestradiol 2-hydroxylation with IC50 of 2 mM; terfenadine hydroxylation with IC50 of 0.14 mM). Ritonavir is also an inhibitor of thereactions mediated by CYP2D6 (IC

7、50=2.5 mM) and CYP2C9/10 (IC50=8.0 mM)2. Ritonavir results in an increase in cellviability in uninfected human PBMC cultures. Ritonavir markedly decreases the susceptibility of PBMCs to apoptosiscorrelated with lower levels of caspase-1 expression, decreases in annexin V staining, and reduces caspas

8、e-3 activityin uninfected human PBMC cultures. Ritonavir inhibits induction of tumor necrosis factor (TNF) production by PBMCsand monocytes in a time- and dose-dependent manner at nontoxic concentrations3. Ritonavir inhibits p-glycoprotein-mediated extrusion of saquinavir with an IC50 of 0.2 M, indi

9、cating a high affinity of ritonavir for p-glycoprotein4. Ritonavir inhibits human liver microsomal metabolism of ABT-378 potently with Ki of 13 nM. Ritonavircombined with ABT-378 (at 3:1 and 29:1 ratios) inhibits CYP3A (IC50=1.1 and 4.6 M), albeit less potently thanRitonavir (IC50=0.14 M)5.戶使本產品發(fā)表的科

10、研獻 Int J Antimicrob Agents. 2019 Dec;54(6):814-819. Antivir Res. 2020 Apr. J Hum Genet. 2019 Oct 23. Drug Metab Dispos. 2019 Jul 2. pii: dmd.119.087684. Chem Cent J. 2017 Jan 3;11:1.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Eagling VA, et al. Differential inhib

11、ition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir. Br J Clin Pharmacol.1997 Aug;44(2):190-4.2. Kumar GN, et al. Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes. J PharmacolExp Ther. 1996

12、 Apr;277(1):423-31.3. Weichold FF, et al. HIV-1 protease inhibitor ritonavir modulates susceptibility to apoptosis of uninfected T cells. J Hum Virol. 1999 Sep-Oct;2(5):261-9.4. Drewe J, et al. HIV protease inhibitor ritonavir: a more potent inhibitor of P-glycoprotein than the cyclosporine analog S

13、DZ PSC 833. Biochem Pharmacol.1999 May 15;57(10):1147-52.5. Kumar GN, et al. Potent inhibition of the cytochrome P-450 3A-mediated human liver microsomal metabolism of a novel HIV protease inhibitor byritonavir: A positive drug-drug interaction. Drug Metab Dispos. 1999 Aug;27(8):902-8.Page 2 of 3 www.MedChemEMcePdfHeightCaution: Produ