1. Anti-infection
  2. Influenza Virus

Pimodivir (Synonyms: VX-787)

Cat. No.: HY-12353A Purity: 99.04%
Data Sheet SDS Handling Instructions

Pimodivir is an orally bioavailable inhibitor of influenza A virus polymerases through interaction with the viral PB2 subunit.

For research use only. We do not sell to patients.
Pimodivir Chemical Structure

Pimodivir Chemical Structure

CAS No. : 1629869-44-8

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Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $105 In-stock
2 mg $90 In-stock
5 mg $120 In-stock
10 mg $190 In-stock
25 mg $350 In-stock
50 mg $540 In-stock
100 mg $940 In-stock
200 mg $1640 In-stock
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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

Pimodivir 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 EC50 value for Pimodivir are 8 and 12 nM for A(H1N1) and A(H3N2) strains, respectively, whereas the CC50 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 is very potent against influenza A strains, including pandemic 2009 H1N1 and avian H5N1[3]. Pimodivir shows potent activity against all influenza A virus strains tested, with an EC50 range of 0.13 to 3.2 nM. Pimodivir-selected PB2 variant viruses maintain susceptibility to neuraminidase inhibitors in vitro[4].

In Vivo

Pimodivir (2, 6, and 20 mg/kg/day, p.o.) and oseltamivir (20 mg/kg/day) completely prevent death in the H1N1pdm virus infection in mice. Pimodivir (20 mg/kg/day) is more effective than oseltamivir (20 mg/kg/day) in improving body weight and reducing the severity of lung infection[1]. Moreover, Pimodivir 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, oseltamivir, provide no survival benefit in this model at 10 mpk[3]. Pimodivir (1, 3, or 10 mg/kg, bid) provided complete survival, with a dose-dependent reduction in BW loss of the mice[4].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT02262715 Janssen Infectious Diseases BVBA Healthy July 2014 Phase 1
NCT01561807 Vertex Pharmaceuticals Incorporated Influenza Virus March 2012 Phase 2
NCT02342249 Janssen Research & Development, LLC|Janssen Pharmaceuticals Influenza A December 11, 2014 Phase 2
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References
Preparing Stock Solutions
Concentration Volume (DMSO) 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
Kinase Assay
[4]

Virus sensitivity to neuraminidase inhibitors is determined by the chemiluminescent neuraminidase inhibitor assay using an NA-XTD kit. Viruses are diluted in NA-XTD assay buffer (26 mM morpholineethanesulfonic acid, 4 mM CaCl2 [pH 6.0]) such that the signal-to-noise ratio is greater than 40:1. Resistance is defined as determination of a 50% inhibitory concentration greater than 10-fold the mean for the type/subtype. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[2]

Pimodivir is dissolved in DMSO.

The compound cytotoxicity and efficacy testing is performed in 96-well plates with macrophages at 95% confluence. The compounds are added to the medium, and 30 min later, the cells are infected with virus or non-infected. The cell viability is analyzed with the Cell Titer Glo assay at 24 hpi. The luminescence is read with a PHERAstar FS plate reader. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

Pimodivir is prepared in 0.5% methylcellulose.

The mice are anesthetized by intraperitoneal injection of ketamine/xylazine (50/5 mg/kg), and the animals are infected intranasally with a 90-μL suspension of influenza virus. The virus challenge is approximately four 50% mouse lethal infectious doses. Treatments are given twice a day (at 12 h intervals) for 10 days starting 2 h before virus challenge. Parameters for assessing the infection are survival, mean day of death, body weight changes, and lung infection parameters (hemorrhage score, weight, and virus titer). Animals are weighed individually every other day through day 21 of the infection. Initially, there are 15 mice per group treated with compound and 25 placebos. Five mice in each group are subsequently sacrificed for determination of lung infection parameters. A larger number of placebos are used than compound-treated mice to achieve greater statistical power, especially if some animals in that group survive the infection. One mouse that dies during the treatment period is presumed to have died from treatment trauma because its death occurs well before other mice die from influenza. It is excluded from the total counts. Animals that die during infection are accounted for in the tabular data. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

399.39

Formula

C₂₀H₁₉F₂N₅O₂

CAS No.

1629869-44-8

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 12.5 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.04%

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Pimodivir
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