法匹拉韋作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetFavipiravirCat. No.: HY-14768CAS No.: 259793-96-9分式: CHFNO分量: 157.1作靶點: DNA/RNA Synthesis; Influenza Virus; SARS-CoV作通路: Cell Cycle/DNA Damage; Anti-infection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 : 100 mg/mL (636.54 mM)H2O : 6.25 mg/mL

2、 (39.78 mM; Need ultrasonic)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 6.3654 mL 31.8269 mL 63.6537 mL5 mM 1.2731 mL 6.3654 mL 12.7307 mL10 mM 0.6365 mL 3.1827 mL 6.3654 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(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -

3、20C, 1 month。-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都請先按?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(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)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/

4、mL (15.91 mM); Clear solution此案可獲得 2.5 mg/mL (15.91 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 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% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (15.91 mM); Clear solutionPage 1 of 2 www.MedChe

5、mE此案可獲得 2.5 mg/mL (15.91 mM，飽和度未知) 的澄清溶液。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。3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (15.91 mM); Clear solution此案可獲得 2.5 mg/mL (15.91 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。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加

6、到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Favipiravir (T-705)種病毒RNA聚合酶 (RNA polymerase) 抑制劑，可轉(zhuǎn)變?yōu)槠浠钚孕问?Favipiravir-ribofuranosyl-5-triphosphate (RTP)。Favipiravir-RTP 抑制流感病毒RNA依賴性的RNA聚合酶 (RdRP) 活性，IC50 為 341 nM。IC & Target IC50: 341 nM (RdRP)1體外研究 Favipiravir (T 705) is an antiviral drug that selectively

7、 inhibits the RNA-dependent RNA polymerase of influenza virus.Favipiravir (T 705) is a novel antiviral compound that selectively and potently inhibits the RNA-dependent RNApolymerase (RdRP) of influenza and many other RNA viruses. Favipiravir-RTP does not inhibit the human DNApolymerase , or with IC

8、501 mM. The IC50 for the human RNA polymerase II is 905 M; Favipiravir is therefore2,650 times more selective for the influenza virus RdRP, consistent with the lack of inhibition of host-cell DNA andRNA synthesis1. Favipiravir (T 705) acts as a pro-drug, its cytotoxicity is expected to be cell-line

9、dependent.Favipiravir inhibits in a dose-dependent manner MNV-induced CPE (EC50: 25011 M) and MNV RNA synthesis in cellculture (EC50:12442 M). Despite this rather modest antiviral activity, Favipiravir (T 705) is able to completely inhibitnorovirus replication at a concentration of 100 g/mL, which i

10、s a concentration that has little or no adverse effect onthe host cell (cell viability 80%)2.體內(nèi)研究 Favipiravir (T 705) (30 mg/kg/day, orally) improves survival compare to placebo. Favipiravir (T 705) also providessignificant protection against the A/Duck/MN/1525/81(H5N1) virus at a dose of 33 mg/kg/d

11、ay or more, regardless ofthe number of daily doses. When given 4 times a day, all mice survive1.PROTOCOLCell Assay 2 The antiviral activity of Favipiravir (T 705) is determined using an MTS-based CPE reduction assay in the MNV/RAW264.7 cell line. To this end, RAW 264.7 cells are seeded (1104 cells/w

12、ell) in 96-well plates and infected with MNV atan MOI of 0,001 in the presence (or absence) of a dilution series of Favipiravir (T 705) (3.13-200 g/mL). Following 3days of incubation, i.e. until complete CPE is observed in infected untreated cells, cell culture supernatants arecollected for quantifi

13、cation of viral RNA load by quantitative RT-PCR (qRT-PCR). For the MTS reduction assay anMTS/Phenazine methosulphate (PMS) stock solution (2 mg/mL MTS and 46 g/mL PMS in PBS at pH 6-6.5) is diluted1/20 in MEM. To each well, 75 L of MTS/PMS solution is added and the optical density (OD) is read at 49

14、8 nm 2 hlater. The % CPE reduction is calculated as (ODtreated)MNWODVC/ODCC-ODVC100, where ODCC represents theOD of the uninfected untreated cells, whereas ODVC and (ODtreated)CC represent the OD of infected untreated cellsand virus-infected cells treated with a compound concentration, respectively.

15、 The EC50 is defined as the compoundconcentration that protected 50% of cells from virus-induced CPE. Adverse effects of the molecule on the host cellare also assessed by means of the MTS-method, by exposing uninfected cells to the same concentrations ofFavipiravir for 3 days. The % cell viability i

16、s calculated as (ODtreated/ODCC)100, where ODCC is the OD of uninfecteduntreated cells and ODtreated are uninfected cells treated with compound. The CC50 is defined as the compoundconcentration that reduces the number of viable cells by 50%. The selectivity index (SI) is calculated as CC50/EC502.Pag

17、e 2 of 3 www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice1Administration 1 Favipiravir (T 705) has also been shown to protect mice against lethal infection by a variety of influenza virus strains.When Favipiravir is orally adminis

18、tered 2 or 4 times a day for 5 days in mice infected with lethal doses of influenzavirus A/Victoria/3/75(H3N2), A/Osaka/5/70(H3N2) or A/Duck/MN/1525/81(H5N1).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(xiàn) Antimicrob Agents Chemother. 2020 Apr 20. pii: AAC.00222-20. Antimicrob Agents Chemother. 2019 May 24;63(6). pii: e00003-19. Antivir Res. 2020 Apr. Antiviral Res. 2018 Jan;149:3