Sofosbuvir-PSI-7977-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESofosbuvirCat. No.: HY-15005CAS No.: 1190307-88-0Synonyms: PSI-7977; GS 7977分式: CHFNOP分量: 529.45作靶点: HCV作通路: Anti-infection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 : 100 mg/mL (188.88

2、mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.8888 mL 9.4438 mL 18.8875 mL5 mM 0.3778 mL 1.8888 mL 3.7775 mL10 mM 0.1889 mL 0.9444 mL 1.8888 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，并请注意储备液的保存式和期限。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，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液

3、可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.72 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.72 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Molec

4、ules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (4.72 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Sofosbuvir (PSI-7977)是HCV RNA复制抑制剂，EC50 为92 nM。IC50 & Target EC50: 925 nM (HCV) 1体外研究 When cathepsin A (CatA) is incubated with PSI-7977 or Sofosbuvir (PSI-7977) for 150 min, 18-fold morePSI-352707 is forme

5、d when Sofosbuvir (PSI-7977) is the substrate compared with PSI-7976. Moreover, thecatalytic efficiency for Sofosbuvir (PSI-7977) with CatA is 30-fold higher than that for PSI-7976 1. Thegenotype coverage of Sofosbuvir (PSI-7977) by using GT 1b (Con1)-, 1a (H77)-, and 2a (JFH-1)-derivedreplicons and

6、 GT 1b chimeric replicons containing the NS5B region from the J6 GT 2a isolate and from GT2b and GT 3a patient isolates is evaluated, Sofosbuvir (PSI-7977) inhibits the replication of these repliconswith similar EC50s (between 16 and 48 nM), and is especially active against the chimeric replicon con

7、tainingthe J6 NS5B (EC50=4.7 nM). Sofosbuvir (PSI-7977) inhibits clone A (GT 1b) wild-type and S282T repliconswith EC90 values of 0.42 and 7.8 M, respectively 2. In the clone A replicon assay, Sofosbuvir (PSI-7977)produces anti-HCV activity with EC90 values 0.42 M 3.PROTOCOLCell Assay 1 Clone A cell

8、s are seeded into T75 flasks at about 5106 cells/flask in Dulbeccos modified Eagles medium(DMEM) containing 100 IU/mL Penicillin/100 g/mL streptomycin and 10% fetal bovine serum. Similarly,human primary hepatocytes are seeded in cell plating medium into T75 flasks at about 5106 cells/flask.After ove

9、rnight incubation to allow the cells to attach, cells are incubated with 50 M PSI-7851, PSI-7976, orSofosbuvir (PSI-7977) in fresh medium for clone A cells or in cell maintenance medium for primaryhepatocytes for up to 24 h at 37C in a 5% CO2 atmosphere. The same procedures are applied whenradiolabe

10、led PSI-7851 is used in the study except that 1106 cells per well are seeded into a 6-well plate,and the cells are incubated with 5 M 3HPSI-7851. At selected times, the medium is removed, and the celllayer is washed with cold phosphate-buffered saline (PBS). After trypsinization, cells are counted a

11、ndcentrifuged at 1,200 rpm for 5 min. The cell pellets are suspended in 1 mL of cold 60% methanol andincubated overnight at 20C. The samples are centrifuged at 14,000 rpm for 5 min, and the supernatantsare collected and dried using a SpeedVac concentrator and stored at 20C until they are analyzed by

12、 highperformance liquid chromatography (HPLC). Residues are suspended in 100 L of water, and 50-L aliquotsare injected into HPLC 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Nat Med. 2014 Aug;20(8):927-35. Nat Immunol. 2017 Dec;18(12):1

13、299-1309. Gastroenterology. 2015 Feb;148(2):392-402.e13.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE Nat Microbiol. 2019 Jul;4(7):1096-1104. Nucleic Acids Res. 2019 Apr 18. pii: gkz278.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Murakami E, et al. Mechanism of activati

14、on of PSI-7851 and its diastereoisomer PSI-7977.J Biol Chem. 2010 Nov 5;285(45):34337-47.2. Lam AM, et al. Genotype and subtype profiling of PSI-7977 as a nucleotide inhibitor of hepatitis C virus. Antimicrob Agents Chemother.2012 Jun;56(6):3359-68.3. Sofia MJ, et al. Discovery of a -d-2-deoxy-2-fluoro-2-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitisC virus. J Med Chem. 2010 Oct 14;53(19):7202-18.4. Zhang X, et al. Discovery and evolution of aloperine derivatives as a new family of HCV inhibitors with novel mechanism. Eur J MedChem. 20