利托那韦作用机制 - Medchemexpress - MCE中国

1、Product Data SheetRitonavirCat. No.: HY-90001CAS No.: 155213-67-5分式: CHNOS分量: 720.94作靶点: HIV Protease; HIV; Apoptosis作通路: Anti-infection; Metabolic Enzyme/Protease; Apoptosis储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 25 mg/mL (34.68 mM; Need ultrasonic)H2O

2、 : 0.1 mg/mL (insoluble)SolventMass1 mg 5 mg 10 mgConcentration制备储备液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请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个

3、内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitro 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (3.47 mM); Suspended solution; Need ultrasonic此案可获

4、得 2.5 mg/mL (3.47 mM) 的均匀悬浊液，悬浊液可于服和腹腔注射。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 20% 的 SBE-CD 理盐溶液中，混合均匀。2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (3.47 mM); Clear solution; Need warmingPage 1 of 2 www.MedChemE此案可获得 2.5 mg/mL (3.47 mM) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取

5、 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L 油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Ritonavir (ABT 538)于治疗HIV感染和AIDS的 HIV蛋酶的抑制剂。体外研究 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.户使本产品发表的科

10、研献 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