化合物PIMODIVIR
化合物PIMODIVIR(Pimodivir)
CAS: 1629869-44-8
化学式: C20H19F2N5O2
| 中文名 | 化合物PIMODIVIR |
| 英文名 | Pimodivir |
| 别名 | 化合物PIMODIVIR |
| 英文别名 | VX-787 CS-2483 Pimodivir VRT-0928787 (2S,3S)-3-[[5-Fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-4-pyrimidinyl]amino]bicyclo[2.2.2]octane-2-carboxylic acid |
| CAS | 1629869-44-8 |
| 化学式 | C20H19F2N5O2 |
| 分子量 | 399.394 |
| 密度 | 1.501±0.06 g/cm3(Predicted) |
| 溶解度 | DMSO: ≥ 12.5 mg/mL |
| 酸度系数 | 4.32±0.40(Predicted) |
| 存储条件 | -20℃ |
| 物化性质 | 生物活性 Pimodivir (VX-787) 是一种可口服的甲型流感病毒聚合酶抑制剂，通过抑制PB2亚基起作用。 |
| 产品用途 | Pimodivir, also known as VX-787, JNJ-872, is a novel inhibitor of influenza virus replication that blocks the PB2 cap-snatching activity of the influenza viral polymerase complex. VX-787 binds the cap-binding domain of the PB2 subunit with a KD (dissociation constant) of 24 nM as determined by isothermal titration calorimetry (ITC). The cell-based EC50 (the concentration of compound that ensures 50% cell viability of an uninfected control) for VX-787 is 1.6 nM in a cytopathic effect (CPE) assay, with a similar EC50 in a viral RNA replication assay. VX-787 is active against a diverse panel of influenza A virus strains, including H1N1pdm09 and H5N1 strains, as well as strains with reduced susceptibility to neuraminidase inhibitors (NAIs). |
| 靶点 | Influenza A polymerases |
| 体外研究 | Pimodivir rescues macrophages from virus-mediated death at non-cytotoxic concentrations 24 hpi. The EC 50 value for Pimodivir are 8 and 12 nM for A(H1N1) and A(H3N2) strains, respectively, whereas the CC 50 values are >1 μM, giving selectivity indexes (SI) > 125 and > 83 for A(H1N1) and A(H3N2) strains, respectively. Pimodivir significantly attenuates the transcription of viral M1 RNA in macrophages, which are infected with A(H1N1) or A(H3N2) strains for 8 h. Pimodivir inhibits the transcription of viral but not cellular genes. Pimodivir allows some activation of IAV-mediated expression of several cellular genes, which are involved in tryptophan and nucleotide metabolism. Pimodivir possesses excellent anti-IAV but not immuno/metabolo-modulating effect. Pimodivir (VX-787) is very potent against influenza A strains, including pandemic 2009 H1N1 and avian H5N1. Pimodivir (VX-787) shows potent activity against all influenza A virus strains tested, with an EC 50 range of 0.13 to 3.2 nM. Pimodivir-selected PB2 variant viruses maintain susceptibility to neuraminidase inhibitors in vitro. |
| 体内研究 | Pimodivir (2, 6, and 20 mg/kg/day, p.o.) and GS 4071 (20 mg/kg/day) completely prevent death in the H1N1pdm virus infection in mice. Pimodivir (20 mg/kg/day) is more effective than GS 4071 (20 mg/kg/day) in improving body weight and reducing the severity of lung infection. Moreover, Pimodivir (VX-787) shows 100% survival in a +48 h delay to treatment mouse influenza model at 10, 3 and 1 mpk (BID × 10 days) whereas the SOC, GS 4071, provide no survival benefit in this model at 10 mpk. Pimodivir (VX-787; 1, 3, or 10 mg/kg, bid) provided complete survival, with a dose-dependent reduction in BW loss of the mice. |
| 参考资料 展开查看 | 1: Boyd MJ, Bandarage UK, Bennett H, Byrn RR, Davies I, Gu W, Jacobs M, Ledeboer MW, Ledford B, Leeman JR, Perola E, Wang T, Bennani Y, Clark MP, Charifson PS. Isosteric replacements of the carboxylic acid of drug candidate VX-787: Effect of charge on antiviral potency and kinase activity of azaindole-based influenza PB2 inhibitors. Bioorg Med Chem Lett. 2015 May 1;25(9):1990-4. doi: 10.1016/j.bmcl.2015.03.013. Erratum in: Bioorg Med Chem Lett. 2016 Jan 1;26(1):240. PubMed PMID: 25827523. 2: Byrn RA, Jones SM, Bennett HB, Bral C, Clark MP, Jacobs MD, Kwong AD, Ledeboer MW, Leeman JR, McNeil CF, Murcko MA, Nezami A, Perola E, Rijnbrand R, Saxena K, Tsai AW, Zhou Y, Charifson PS. Preclinical activity of VX-787, a first-in-class, orally bioavailable inhibitor of the influenza virus polymerase PB2 subunit. Antimicrob Agents Chemother. 2015 Mar;59(3):1569-82. doi: 10.1128/AAC.04623-14. PubMed PMID: 25547360; PubMed Central PMCID: PMC4325764. 3: Clark MP, Ledeboer MW, Davies I, Byrn RA, Jones SM, Perola E, Tsai A, Jacobs M, Nti-Addae K, Bandarage UK, Boyd MJ, Bethiel RS, Court JJ, Deng H, Duffy JP, Dorsch WA, Farmer LJ, Gao H, Gu W, Jackson K, Jacobs DH, Kennedy JM, Ledford B, Liang J, Maltais F, Murcko M, Wang T, Wannamaker MW, Bennett HB, Leeman JR, McNeil C, Taylor WP, Memmott C, Jiang M, Rijnbrand R, Bral C, Germann U, Nezami A, Zhang Y, Salituro FG, Bennani YL, Charifson PS. Discovery of a novel, first-in-class, orally bioavailable azaindole inhibitor (VX-787) of influenza PB2. J Med Chem. 2014 |
化合物PIMODIVIR - 配置溶液浓度参考
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.504 ml | 12.519 ml | 25.038 ml |
| 5 mM | 0.501 ml | 2.504 ml | 5.008 ml |
| 10 mM | 0.25 ml | 1.252 ml | 2.504 ml |
| 5 mM | 0.05 ml | 0.25 ml | 0.501 ml |
最后更新：2024-01-02 23:10:35
化合物PIMODIVIR - 动物实验
The mice, infected intranasally with influenza virus, are given Pimodivir(prepared in 0.5% methylcellulose) twice a day.
最后更新：2023-08-16 21:32:38
供应商列表
您刚刚浏览过
你知道吗？
微信搜索化工百科或扫描下方二维码，添加化工百科小程序，随时随地查信息！