[CAS NO. 1629869-44-8] Pimodivir
PRODUCTS SPECIFICATIONS [1629869-44-8]
DESCRIPTION [1629869-44-8]
Overview
| MDL | MFCD31382121 |
|---|---|
| Molecular Weight | 399.39 |
| Molecular Formula | C20H19F2N5O2 |
| SMILES | O=C([C@H]1C(CC2)CCC2[C@@H]1NC3=NC(C4=CNC5=NC=C(F)C=C54)=NC=C3F)O |
3 Publications Citing Use of MCE
Summary
Pimodivir (VX-787) is an orally bioavailable inhibitor of influenza A virus polymerases through interaction with the viral PB2 subunit.
In Vitro
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 [2] . Pimodivir (VX-787) is very potent against influenza A strains, including pandemic 2009 H1N1 and avian H5N1 [3] . 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 [4] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
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 [1] . 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 [3] . Pimodivir (VX-787; 1, 3, or 10 mg/kg, bid) provided complete survival, with a dose-dependent reduction in BW loss of the mice [4] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT03947814 | Janssen-Cilag International NV |
Kidney Failure, Chronic
|
July 2, 2019 | Phase 1 |
| NCT03816631 | Janssen-Cilag International NV |
Hepatic Impairment
|
May 28, 2019 | Phase 1 |
| NCT02262715 | Janssen Infectious Diseases BVBA |
Healthy
|
July 2014 | Phase 1 |
| NCT03768609 | Janssen-Cilag International NV |
Healthy
|
December 6, 2018 | Phase 1 |
| NCT03381196 | Janssen Research & Development, LLC |
Influenza A
|
January 21, 2018 | Phase 3 |
| NCT01561807 | Vertex Pharmaceuticals Incorporated |
Influenza Virus
|
March 2012 | Phase 2 |
| NCT02342249 | Janssen Research & Development, LLC|Janssen Pharmaceuticals |
Influenza A
|
December 11, 2014 | Phase 2 |
| NCT03376321 | Janssen Research & Development, LLC |
Influenza A
|
January 3, 2018 | Phase 3 |
| NCT03834376 | Janssen Research & Development, LLC |
H7N9 Subtype of Influenza A Virus
|
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 5 mg/mL ( 12.52 mM ; ultrasonic and warming and heat to 60°C)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.5038 mL | 12.5191 mL | 25.0382 mL |
| 5 mM | 0.5008 mL | 2.5038 mL | 5.0076 mL |
| 10 mM | 0.2504 mL | 1.2519 mL | 2.5038 mL |
References
- [1] Smee DF, et al. Activities of JNJ63623872 and GS 4071 against influenza A H1N1pdm and H3N2 virus infections in mice. Antiviral Res. 2016 Dec;136:45-50.
- [2] Fu Y, et al. JNJ872 inhibits influenza A virus replication without altering cellular antiviral responses. Antiviral Res. 2016 Sep;133:23-31.
- [3] Boyd MJ, et al. 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.
- [4] Byrn RA, et al. 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.