CS-2483
Pimodivir
CAS: 1629869-44-8
Molecular Formula: C20H19F2N5O2
CS-2483 - Names and Identifiers
| Name | Pimodivir |
| Synonyms | 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 |
CS-2483 - Physico-chemical Properties
| Molecular Formula | C20H19F2N5O2 |
| Molar Mass | 399.394 |
| Density | 1.501±0.06 g/cm3(Predicted) |
| Solubility | DMSO: ≥ 12.5 mg/mL |
| pKa | 4.32±0.40(Predicted) |
| Storage Condition | -20℃ |
| Physical and Chemical Properties | Bioactive Pimodivir (VX-787) is an orally available inhibitor of influenza A Virus polymerase that acts by inhibiting the PB2 subunit. |
| Use | 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). |
| Target | Influenza A polymerases |
| In vitro study | 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. |
| In vivo study | 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. |
CS-2483 - Reference
| Reference Show more | 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 |
CS-2483 - Preparation solution concentration reference
| 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 |
Last Update：2024-01-02 23:10:35
CS-2483 - Animal Experiment
The mice, infected intranasally with influenza virus, are given Pimodivir(prepared in 0.5% methylcellulose) twice a day.
Last Update：2023-08-16 21:32:38
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Product Name: Pimodivir Visit Supplier Webpage Request for quotation
CAS: 1629869-44-8
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
CAS: 1629869-44-8
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
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