| Size | Price | Stock | Qty |
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| 25mg |
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| Targets |
Pimodivir targets the influenza virus polymerase basic protein 2 (PB2) subunit, a component of the viral RNA-dependent RNA polymerase complex. PB2 is responsible for the "cap-snatching" mechanism by which the virus acquires 5' caps from host mRNAs to prime viral transcription. Pimodivir binds to the PB2 subunit with a Kd of <3 nM and inhibits viral replication.
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| ln 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 (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 EC50 range of 0.13 to 3.2 nM.
Pimodivir-selected PB2 variant viruses maintain susceptibility to
neuraminidase inhibitors in vitro[4].
In vitro, Pimodivir shows potent activity against all influenza A virus strains tested, with an EC₅₀ range of 0.13 to 3.2 nM. The compound is a PB2 inhibitor with a Kd of <3 nM. Pimodivir-selected PB2 variant viruses maintain susceptibility to neuraminidase inhibitors in vitro, indicating a distinct mechanism of action from existing antivirals. |
| ln 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 (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, oseltamivir, 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].
In vivo, Pimodivir (1, 3, or 10 mg/kg, administered twice daily) provides complete survival in influenza-infected mice, with a dose-dependent reduction in body weight loss. As an orally bioavailable inhibitor, it demonstrates efficacy in preclinical models of influenza A infection. Its antiviral activity has been validated in animal models, supporting its clinical development. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for Pimodivir involve measuring its binding affinity to the influenza virus PB2 subunit. Binding affinity (Kd) is determined using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). Antiviral activity is assessed using cytopathic effect (CPE) inhibition assays in influenza-infected cell lines, with EC₅₀ values calculated from concentration-response curves.
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| Cell Assay |
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.
In vitro cellular assays for Pimodivir are performed using influenza A virus-infected cell lines. Cells are treated with the compound at various concentrations, and viral replication is measured by quantifying viral RNA, viral protein expression, or cytopathic effect. The EC₅₀ for inhibition of viral replication is calculated from concentration-response curves. |
| Animal Protocol |
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.
In vivo animal experiments for Pimodivir are conducted in mouse models of influenza A infection. A typical protocol involves administration of the compound (1, 3, or 10 mg/kg, twice daily) to infected mice, followed by assessment of survival rates, body weight changes, and viral titers in lung tissues. Efficacy is compared to vehicle controls and standard-of-care antivirals. |
| ADME/Pharmacokinetics |
Pimodivir is an orally bioavailable inhibitor of influenza virus replication. It has a molecular weight of 399.42 and molecular formula C₂₀H₁₉F₂N₅O₂. The compound is supplied as a solid with purity ≥98% and is soluble in DMSO. It displays λmax at 222 and 263 nm and should be stored at -20°C.
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| Toxicity/Toxicokinetics |
Toxicological data for Pimodivir have been evaluated in preclinical studies to support its clinical development. As an antiviral agent, its safety profile is characterized by its effects on viral polymerase inhibition. Specific toxicity data, including organ-specific effects and dose-limiting toxicities, are available from regulatory submissions.
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| References |
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| Additional Infomation |
Pimodivir is being investigated in the clinical trial NCT02658825 (a study evaluating the effects of JNJ-63623872 on cardiac repolarization interval in healthy subjects). Pimodivir is a highly bioavailable, oral non-nucleoside inhibitor that inhibits the polymerase basic protein 2 (PB2) subunit of the influenza A virus polymerase complex, exhibiting potential antiviral activity. After administration, pimodivir occupies the 7-methyl GTP (m7GTP) binding site of PB2, thereby blocking the "cap-grabbing" activity of the influenza virus polymerase complex and inhibiting viral mRNA synthesis. PB2 is one of the three subunits constituting the influenza A virus polymerase complex, which is responsible for replication and transcription of the viral RNA (vRNA) genome within the nucleus of infected cells.
Drug Indications Treatment of Influenza Pimodivir is also known as JNJ 63623872, JNJ 872, and VX 787. It was developed as a first-in-class influenza A virus PB2 inhibitor. The compound has been investigated in clinical trials for the treatment of influenza A infection. It is a research compound not approved for clinical use in all jurisdictions. |
| Molecular Formula |
C20H19F2N5O2
|
|---|---|
| Molecular Weight |
399.4018
|
| Exact Mass |
399.15
|
| Elemental Analysis |
C, 60.14; H, 4.80; F, 9.51; N, 17.53; O, 8.01
|
| CAS # |
1629869-44-8
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| Related CAS # |
1777721-70-6 (HCl);1629869-44-8;1777814-27-3;
|
| PubChem CID |
67286591
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| Appearance |
White to light yellow solid powder
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| Density |
1.5±0.1 g/cm3
|
| Boiling Point |
574.1±50.0 °C at 760 mmHg
|
| Flash Point |
301.0±30.1 °C
|
| Vapour Pressure |
0.0±1.7 mmHg at 25°C
|
| Index of Refraction |
1.688
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| LogP |
2.81
|
| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
620
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
FC1=C([H])N=C(C2=C([H])N([H])C3=C2C([H])=C(C([H])=N3)F)N=C1N([H])[C@]1([H])[C@@]([H])(C(=O)O[H])C2([H])C([H])([H])C([H])([H])C1([H])C([H])([H])C2([H])[H]
|
| InChi Key |
JGPXDNKSIXAZEQ-SBBZOCNPSA-N
|
| InChi Code |
InChI=1S/C20H19F2N5O2/c21-11-5-12-13(7-24-17(12)23-6-11)18-25-8-14(22)19(27-18)26-16-10-3-1-9(2-4-10)15(16)20(28)29/h5-10,15-16H,1-4H2,(H,23,24)(H,28,29)(H,25,26,27)/t9?,10?,15-,16-/m0/s1
|
| Chemical Name |
(2S,3S)-3-((5-Fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylic Acid
|
| Synonyms |
VX-787; VX 787; VX787; JNJ-63623872; JNJ63623872; JNJ 63623872; JNJ-872; JNJ 872; JNJ872; VRT-0928787; VRT 0928787; VRT0928787; pimodivir
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~5 mg/mL (~12.52 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5038 mL | 12.5188 mL | 25.0376 mL | |
| 5 mM | 0.5008 mL | 2.5038 mL | 5.0075 mL | |
| 10 mM | 0.2504 mL | 1.2519 mL | 2.5038 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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