Pimodivir | VX-787 | CAS# 1629869-44-8 | Influenza Virus Inhibitor

MedKoo Cat#: 522612 | Name: VX-787

Description:

WARNING: This product is for research use only, not for human or veterinary 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).

Chemical Structure

VX-787

CAS#1629869-44-8 (free base)

Theoretical Analysis

MedKoo Cat#: 522612

Name: VX-787

CAS#: 1629869-44-8 (free base)

Chemical Formula: C20H19F2N5O2

Exact Mass: 399.1507

Molecular Weight: 399.40

Elemental Analysis: C, 60.14; H, 4.80; F, 9.51; N, 17.53; O, 8.01

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship
500mg	USD 2,750.00	Ready to ship
1g	USD 3,850.00	Ready to ship

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Related CAS #

1777721-70-6 (HCl) 1629869-44-8 (free base) 1777814-27-3 (tosylate)

Synonym

VX-787; VX 787; VX787; JNJ-63623872; JNJ63623872; JNJ 63623872; JNJ-872; JNJ 872; JNJ872; VRT-0928787; VRT 0928787; VRT0928787; Pimodivir

IUPAC/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

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

SMILES Code

O=C([C@H]1C(CC2)CCC2[C@@H]1NC3=NC(C4=CNC5=NC=C(F)C=C54)=NC=C3F)O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#IPL60609

QC Data

View QC data: current batch, Lot#IPL60609

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Pimodivir (VX-787) is an orally bioavailable inhibitor of influenza A virus polymerases through interaction with the viral PB2 subunit.

In vitro activity:

Pimodivir (VX-787) 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. Reference: Antiviral Res. 2016 Sep;133:23-31. https://www.sciencedirect.com/science/article/pii/S0166354216302583?via%3Dihub

In vivo activity:

VX-787 shows consistent activity against the H1N1pdm09 strain and a highly pathogenic avian influenza virus A/Viet Nam/1203/2004 strain. PB2 has been reported to play a significant role in host restriction (57, 58), with a K627E substitution observed in avian strains relative to human-derived strains. VX-787 is equally effective against strains containing this K627E variant, which is outside the PB2 cap-binding site (data not shown). Targeting PB2 instead of neuraminidase in the influenza virus replication cycle provides several unique opportunities. At any point during the course of disease in vivo, there are both infected cells that need to be controlled and as-yet-uninfected cells that need to be protected; VX-787 has the potential to perform both functions. The means by which VX-787 blocks CPE in infected cells could simply be inhibition of (+)-strand viral RNA synthesis, but it is possible that other mechanisms, such as interference with influenza virus-induced host cell shutoff, are involved (59, 60). Many details of the function of PB2 remain to be elucidated. The effect of VX-787 on lung viral loads in mice is positive. At several different doses, VX-787 showed a 1 to >5 log viral load reduction relative to vehicle controls. Administration of VX-787 provides a rapid reduction in the amount of influenza A virus in the lungs of infected mice and suggests a direct effect on viral replication. This result is consistent with the observed MOI independence of VX-787; initially infected lung cells may create a local high-MOI environment that would remain under antiviral suppression by VX-787 but not be suppressed by oseltamivir. The results from this series of studies represent the first evidence that a pharmacologic inhibitor of influenza A virus PB2 effectively inhibits viral replication in vivo and successfully abrogates or attenuates influenza virus infection in mouse models of the disease. Reference: Antimicrob Agents Chemother. 2015 Mar;59(3):1569-82. https://aac.asm.org/content/59/3/1569

	Solvent	mg/mL	mM
Solubility
	Soluble in DMSO, not in water	100.0	250.38

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 399.40 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Fu Y, Gaelings L, Söderholm S, Belanov S, Nandania J, Nyman TA, Matikainen S, Anders S, Velagapudi V, Kainov DE. JNJ872 inhibits influenza A virus replication without altering cellular antiviral responses. Antiviral Res. 2016 Sep;133:23-31. doi: 10.1016/j.antiviral.2016.07.008. Epub 2016 Jul 20. PMID: 27451344. 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. Epub 2014 Dec 29. PMID: 25547360; PMCID: PMC4325764. 3. 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. Epub 2014 Dec 29. PMID: 25547360; PMCID: PMC4325764. 4. Smee DF, Barnard DL, Jones SM. Activities of JNJ63623872 and oseltamivir against influenza A H1N1pdm and H3N2 virus infections in mice. Antiviral Res. 2016 Dec;136:45-50. doi: 10.1016/j.antiviral.2016.10.009. Epub 2016 Oct 19. PMID: 27771390.

In vitro protocol:

In vivo protocol:

1. 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. Epub 2014 Dec 29. PMID: 25547360; PMCID: PMC4325764. 2. Smee DF, Barnard DL, Jones SM. Activities of JNJ63623872 and oseltamivir against influenza A H1N1pdm and H3N2 virus infections in mice. Antiviral Res. 2016 Dec;136:45-50. doi: 10.1016/j.antiviral.2016.10.009. Epub 2016 Oct 19. PMID: 27771390.

1: Ianevski A, Yao R, Zusinaite E, Lello LS, Wang S, Jo E, Yang J, Ravlo E, Wang W, Lysvand H, Løseth K, Oksenych V, Tenson T, Windisch MP, Poranen MM, Nieminen AI, Nordbø SA, Fenstad MH, Grødeland G, Aukrust P, Trøseid M, Kantele A, Lastauskienė E, Vitkauskienė A, Legrand N, Merits A, Bjørås M, Kainov DE. Synergistic Interferon-Alpha-Based Combinations for Treatment of SARS-CoV-2 and Other Viral Infections. Viruses. 2021 Dec 11;13(12):2489. doi: 10.3390/v13122489. PMID: 34960758; PMCID: PMC8705725. 2: Soh YQS, Malone KD, Eguia RT, Bloom JD. Comprehensive Profiling of Mutations to Influenza Virus PB2 That Confer Resistance to the Cap-Binding Inhibitor Pimodivir. Viruses. 2021 Jun 22;13(7):1196. doi: 10.3390/v13071196. PMID: 34206520; PMCID: PMC8310130. 3: Mengual-Chuliá B, Alonso-Cordero A, Cano L, Mosquera MDM, de Molina P, Vendrell R, Reyes-Prieto M, Jané M, Torner N, Martínez AI, Vila J, Díez-Domingo J, Marcos MÁ, López-Labrador FX. Whole-Genome Analysis Surveillance of Influenza A Virus Resistance to Polymerase Complex Inhibitors in Eastern Spain from 2016 to 2019. Antimicrob Agents Chemother. 2021 May 18;65(6):e02718-20. doi: 10.1128/AAC.02718-20. PMID: 33782005; PMCID: PMC8315920. 4: Gregor J, Radilová K, Brynda J, Fanfrlík J, Konvalinka J, Kožíšek M. Structural and Thermodynamic Analysis of the Resistance Development to Pimodivir (VX-787), the Clinical Inhibitor of Cap Binding to PB2 Subunit of Influenza A Polymerase. Molecules. 2021 Feb 14;26(4):1007. doi: 10.3390/molecules26041007. PMID: 33673017; PMCID: PMC7917969. 5: Patel MC, Chesnokov A, Jones J, Mishin VP, De La Cruz JA, Nguyen HT, Zanders N, Wentworth DE, Davis TC, Gubareva LV. Susceptibility of widely diverse influenza a viruses to PB2 polymerase inhibitor pimodivir. Antiviral Res. 2021 Apr;188:105035. doi: 10.1016/j.antiviral.2021.105035. Epub 2021 Feb 10. PMID: 33581212. 6: O'Neil B, Ison MG, Hallouin-Bernard MC, Nilsson AC, Torres A, Wilburn JM, van Duijnhoven W, Van Dromme I, Anderson D, Deleu S, Kosoglou T, Vingerhoets J, Rossenu S, Leopold L. A Phase 2 Study of Pimodivir (JNJ-63623872) in Combination with Oseltamivir in Elderly and NonElderly Adults Hospitalized with Influenza A Infection: OPAL study. J Infect Dis. 2020 Jun 30:jiaa376. doi: 10.1093/infdis/jiaa376. Epub ahead of print. PMID: 32604406. 7: Takashita E. Influenza Polymerase Inhibitors: Mechanisms of Action and Resistance. Cold Spring Harb Perspect Med. 2021 May 3;11(5):a038687. doi: 10.1101/cshperspect.a038687. PMID: 32122918; PMCID: PMC8091960. 8: O'Sullivan S, Torres A, Rodriguez A, Martin-Loeches I. Influenza management with new therapies. Curr Opin Pulm Med. 2020 May;26(3):215-221. doi: 10.1097/MCP.0000000000000667. PMID: 32068576. 9: McGowan DC, Balemans W, Embrechts W, Motte M, Keown JR, Buyck C, Corbera J, Funes M, Moreno L, Cooymans L, Tahri A, Eymard J, Stoops B, Strijbos R, Van den Berg J, Fodor E, Grimes JM, Koul A, Jonckers THM, Raboisson P, Guillemont J. Design, Synthesis, and Biological Evaluation of Novel Indoles Targeting the Influenza PB2 Cap Binding Region. J Med Chem. 2019 Nov 14;62(21):9680-9690. doi: 10.1021/acs.jmedchem.9b01091. Epub 2019 Oct 30. PMID: 31647875; PMCID: PMC7611167. 10: Zhang H, Zhou L, Amichai S, Zandi K, Cox B, Schinazi R, Amblard F. Novel influenza polymerase PB2 inhibitors for the treatment of influenza A infection. Bioorg Med Chem Lett. 2019 Oct 15;29(20):126639. doi: 10.1016/j.bmcl.2019.126639. Epub 2019 Aug 24. PMID: 31493987; PMCID: PMC7732027. 11: Mifsud EJ, Hayden FG, Hurt AC. Antivirals targeting the polymerase complex of influenza viruses. Antiviral Res. 2019 Sep;169:104545. doi: 10.1016/j.antiviral.2019.104545. Epub 2019 Jun 25. PMID: 31247246. 12: Pavia A. One hundred years after the 1918 pandemic: new concepts for preparing for influenza pandemics. Curr Opin Infect Dis. 2019 Aug;32(4):365-371. doi: 10.1097/QCO.0000000000000564. PMID: 31116135. 13: Beigel JH, Nam HH, Adams PL, Krafft A, Ince WL, El-Kamary SS, Sims AC. Advances in respiratory virus therapeutics - A meeting report from the 6th isirv Antiviral Group conference. Antiviral Res. 2019 Jul;167:45-67. doi: 10.1016/j.antiviral.2019.04.006. Epub 2019 Apr 8. PMID: 30974127; PMCID: PMC7132446. 14: Hayden FG, Shindo N. Influenza virus polymerase inhibitors in clinical development. Curr Opin Infect Dis. 2019 Apr;32(2):176-186. doi: 10.1097/QCO.0000000000000532. PMID: 30724789; PMCID: PMC6416007. 15: Finberg RW, Lanno R, Anderson D, Fleischhackl R, van Duijnhoven W, Kauffman RS, Kosoglou T, Vingerhoets J, Leopold L. Phase 2b Study of Pimodivir (JNJ-63623872) as Monotherapy or in Combination With Oseltamivir for Treatment of Acute Uncomplicated Seasonal Influenza A: TOPAZ Trial. J Infect Dis. 2019 Mar 15;219(7):1026-1034. doi: 10.1093/infdis/jiy547. PMID: 30428049. 16: Deleu S, Kakuda TN, Spittaels K, Vercauteren JJ, Hillewaert V, Lwin A, Leopold L, Hoetelmans RMW. Single- and multiple-dose pharmacokinetics and safety of pimodivir, a novel, non-nucleoside polymerase basic protein 2 subunit inhibitor of the influenza A virus polymerase complex, and interaction with oseltamivir: a Phase 1 open-label study in healthy volunteers. Br J Clin Pharmacol. 2018 Nov;84(11):2663-2672. doi: 10.1111/bcp.13733. Epub 2018 Sep 14. PMID: 30098042; PMCID: PMC6177716. 17: Trevejo JM, Asmal M, Vingerhoets J, Polo R, Robertson S, Jiang Y, Kieffer TL, Leopold L. Pimodivir treatment in adult volunteers experimentally inoculated with live influenza virus: a Phase IIa, randomized, double-blind, placebo- controlled study. Antivir Ther. 2018;23(4):335-344. doi: 10.3851/IMP3212. PMID: 29244026. 18: Pflug A, Gaudon S, Resa-Infante P, Lethier M, Reich S, Schulze WM, Cusack S. Capped RNA primer binding to influenza polymerase and implications for the mechanism of cap-binding inhibitors. Nucleic Acids Res. 2018 Jan 25;46(2):956-971. doi: 10.1093/nar/gkx1210. PMID: 29202182; PMCID: PMC5778463. 19: McKimm-Breschkin JL, Jiang S, Hui DS, Beigel JH, Govorkova EA, Lee N. Prevention and treatment of respiratory viral infections: Presentations on antivirals, traditional therapies and host-directed interventions at the 5th ISIRV Antiviral Group conference. Antiviral Res. 2018 Jan;149:118-142. doi: 10.1016/j.antiviral.2017.11.013. Epub 2017 Nov 21. PMID: 29162476; PMCID: PMC7133686. 20: Smee DF, Barnard DL, Jones SM. Activities of JNJ63623872 and oseltamivir against influenza A H1N1pdm and H3N2 virus infections in mice. Antiviral Res. 2016 Dec;136:45-50. doi: 10.1016/j.antiviral.2016.10.009. Epub 2016 Oct 19. PMID: 27771390.