Favipiravir
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Identification
- Summary
Favipiravir is an antiviral used to manage influenza, and that has the potential to target other viral infections.
- Generic Name
- Favipiravir
- DrugBank Accession Number
- DB12466
- Background
Discovered by Toyama Chemical Co., Ltd. in Japan, favipiravir is a modified pyrazine analog that was initially approved for therapeutic use in resistant cases of influenza.7,9 The antiviral targets RNA-dependent RNA polymerase (RdRp) enzymes, which are necessary for the transcription and replication of viral genomes.7,12,13
Not only does favipiravir inhibit replication of influenza A and B, but the drug has shown promise in the treatment of avian influenza, and may be an alternative option for influenza strains that are resistant to neuramidase inhibitors.9,19 Favipiravir has been investigated for the treatment of life-threatening pathogens such as Ebola virus, Lassa virus, and now COVID-19.10,14,15
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 157.104
Monoisotopic: 157.028754544 - Chemical Formula
- C5H4FN3O2
- Synonyms
- Fapilavir
- Favilavir
- Favipiravir
- External IDs
- T 705
- T-705
- T705
Pharmacology
- Indication
In 2014, favipiravir was approved in Japan to treat cases of influenza that were unresponsive to conventional treatment.9 Given its efficacy at targetting several strains of influenza, it has been investigated in other countries to treat novel viruses including Ebola and most recently, COVID-19.7,10,17
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Treatment resistant novel influenza •••••••••••• Treatment of Treatment resistant reemerging influenza •••••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Favipiravir functions as a prodrug and undergoes ribosylation and phosphorylation intracellularly to become the active favipiravir-RTP.7,10 Favipiravir-RTP binds to and inhibits RNA dependent RNA polymerase (RdRp), which ultimately prevents viral transcription and replication.7,8
- Mechanism of action
The mechanism of action of favipiravir is novel compared to existing influenza antivirals that primarily prevent entry and exit of the virus from cells.7 The active favipiravir-RTP selectively inhibits RNA polymerase and prevents replication of the viral genome.18 There are several hypotheses as to how favipiravir-RTP interacts with RNA dependent RNA polymerase (RdRp).7 Some studies have shown that when favipiravir-RTP is incorporated into a nascent RNA strand, it prevents RNA strand elongation and viral proliferation.7 Studies have also found that the presence of purine analogs can reduce favipiravir’s antiviral activity, suggesting competition between favipiravir-RTP and purine nucleosides for RdRp binding.7
Although favipiravir was originally developed to treat influenza, the RdRp catalytic domain (favipiravir's primary target), is expected to be similar for other RNA viruses.7 This conserved RdRp catalytic domain contributes to favipiravir's broad-spectrum coverage.7
Target Actions Organism ADNA-directed RNA polymerase subunit beta modulatorMycobacterium tuberculosis (strain ATCC 25618 / H37Rv) ADNA-directed RNA polymerase subunit beta' modulatorMycobacterium tuberculosis ARNA-directed RNA polymerase catalytic subunit Not Available Influenza A virus (strain A/Silky Chicken/Hong Kong/SF189/2001 H5N1 genotype A) - Absorption
The bioavailability of favipiravir is almost complete at 97.6%.18 The mean Cmax for the recommended dosing schedule of favipiravir is 51.5 ug/mL.18
Studies comparing the pharmacokinetic effects of multiple doses of favipiravir in healthy American and Japanese subjects are below:
Japanese subjects First Dose: Cmax = 36.24 ug/mL tmax = 0.5 hr AUC = 91.40 ugxhr/mL
American subjects First Dose: Cmax = 22.01 ug/mL tmax = 0.5 hr AUC = 44.11 ugxhr/mL
Japanese Subjects Final Dose: Cmax = 36.23 ug/mL Tmax = 0.5 hr AUC = 215.05 ugxhr/mL
American Subjects Final Dose: Cmax = 23.94 ug/mL Tmax = 0.6 hr AUC = 73.27 ugxhr/mL
When favipiravir was given as a single dose of 400 mg with food, the Cmax decreased.18 It appears that when favipiravir is given at a higher dose or in multiple doses, irreversible inhibition of aldehyde oxidase (AO) occurs and the effect of food on the Cmax is lessened.18
- Volume of distribution
The apparent volume of distribution of favipiravir is 15 - 20 L.11
- Protein binding
Favipiravir is 54% plasma protein-bound.9 Of this fraction, 65% is bound to serum albumin and 6.5% is bound to ɑ1-acid glycoprotein.18
- Metabolism
Favipiravir is extensively metabolized with metabolites excreted mainly in the urine.10 The antiviral undergoes hydroxylation primarily by aldehyde oxidase and to a lesser extent by xanthine oxidase to the inactive metabolite, T705M1.10
Hover over products below to view reaction partners
- Route of elimination
Favipiravir's metabolites are predominantly renally cleared.9
- Half-life
The elimination half-life of favipiravir is estimated to range from 2 to 5.5 hours.9
- Clearance
The recommended oral dosing regimen for favipiravir is as follows: Day 1: 1600 mg twice daily; Days 2-5: 600 mg twice daily.18
The reported CL/F for favipiravir 1600 mg dosed once daily is 2.98 L/hr ±0.30 and the CL/F values for favipiravir 600 mg dosed twice daily on days 1-2 and once daily on days 3-7 were 6.72 L/hr ±1.68 on Day 1, and 2.89 L/hr ±0.91 on Day 7.18 There is currently no reported clearance data for favipiravir 1600 mg dosed twice daily.
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Based on single-dose toxicity studies, the lethal dose for oral and intravenous favipiravir in mice is estimated to be >2000 mg/kg.18 In rats, the lethal dose for oral administration is >2000 mg/kg, while the lethal dose in dogs and monkeys is >1000 mg/kg.18 Symptoms of overdose appear to include but are not limited to reduced body weight, vomiting, and decreased locomotor activity.18
In repeat-dose toxicity studies involving dogs, rats, and monkeys, notable findings after administration of oral favipiravir included: adverse effects on hematopoietic tissues such as decreased red blood cell (RBC) production, and increases in liver function parameters such as aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and total bilirubin, and increased vacuolization in hepatocytes.18 Testis toxicity was also noted.18
Favipiravir is known to be teratogenic; therefore, administration of favipiravir should be avoided in women if pregnancy is confirmed or suspected.7,16
Toxicity information regarding favipiravir in humans is not readily available.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Favipiravir. Acamprosate The excretion of Acamprosate can be decreased when combined with Favipiravir. Acetaminophen Favipiravir may increase the hepatotoxic activities of Acetaminophen. Acyclovir The excretion of Acyclovir can be decreased when combined with Favipiravir. Adefovir dipivoxil The excretion of Adefovir dipivoxil can be decreased when combined with Favipiravir. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Avigan
Categories
- ATC Codes
- J05AX27 — Favipiravir
- Drug Categories
- Anti-Infective Agents
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2E1 Inhibitors
- Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Direct Acting Antivirals
- Experimental Unapproved Treatments for COVID-19
- OAT1/SLC22A6 inhibitors
- OAT3/SLC22A8 Inhibitors
- P-glycoprotein inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyrazinecarboxamides. These are compounds containing a pyrazine ring which bears a carboxamide.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazines
- Sub Class
- Pyrazines
- Direct Parent
- Pyrazinecarboxamides
- Alternative Parents
- 2-heteroaryl carboxamides / Aryl fluorides / Vinylogous amides / Heteroaromatic compounds / Primary carboxylic acid amides / Lactams / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds show 3 more
- Substituents
- 2-heteroaryl carboxamide / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle / Carboxamide group / Carboxylic acid derivative / Heteroaromatic compound / Hydrocarbon derivative / Lactam show 11 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- EW5GL2X7E0
- CAS number
- 259793-96-9
- InChI Key
- ZCGNOVWYSGBHAU-UHFFFAOYSA-N
- InChI
- InChI=1S/C5H4FN3O2/c6-2-1-8-5(11)3(9-2)4(7)10/h1H,(H2,7,10)(H,8,11)
- IUPAC Name
- 6-fluoro-3-hydroxypyrazine-2-carboxamide
- SMILES
- NC(=O)C1=NC(F)=CN=C1O
References
- General References
- Beigel J, Bray M: Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Res. 2008 Apr;78(1):91-102. doi: 10.1016/j.antiviral.2008.01.003. Epub 2008 Feb 4. [Article]
- Hsieh HP, Hsu JT: Strategies of development of antiviral agents directed against influenza virus replication. Curr Pharm Des. 2007;13(34):3531-42. [Article]
- Gowen BB, Wong MH, Jung KH, Sanders AB, Mendenhall M, Bailey KW, Furuta Y, Sidwell RW: In vitro and in vivo activities of T-705 against arenavirus and bunyavirus infections. Antimicrob Agents Chemother. 2007 Sep;51(9):3168-76. Epub 2007 Jul 2. [Article]
- Sidwell RW, Barnard DL, Day CW, Smee DF, Bailey KW, Wong MH, Morrey JD, Furuta Y: Efficacy of orally administered T-705 on lethal avian influenza A (H5N1) virus infections in mice. Antimicrob Agents Chemother. 2007 Mar;51(3):845-51. Epub 2006 Dec 28. [Article]
- Furuta Y, Takahashi K, Kuno-Maekawa M, Sangawa H, Uehara S, Kozaki K, Nomura N, Egawa H, Shiraki K: Mechanism of action of T-705 against influenza virus. Antimicrob Agents Chemother. 2005 Mar;49(3):981-6. [Article]
- Furuta Y, Takahashi K, Fukuda Y, Kuno M, Kamiyama T, Kozaki K, Nomura N, Egawa H, Minami S, Watanabe Y, Narita H, Shiraki K: In vitro and in vivo activities of anti-influenza virus compound T-705. Antimicrob Agents Chemother. 2002 Apr;46(4):977-81. [Article]
- Furuta Y, Komeno T, Nakamura T: Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(7):449-463. doi: 10.2183/pjab.93.027. [Article]
- Venkataraman S, Prasad BVLS, Selvarajan R: RNA Dependent RNA Polymerases: Insights from Structure, Function and Evolution. Viruses. 2018 Feb 10;10(2). pii: v10020076. doi: 10.3390/v10020076. [Article]
- 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. [Article]
- Madelain V, Nguyen TH, Olivo A, de Lamballerie X, Guedj J, Taburet AM, Mentre F: Ebola Virus Infection: Review of the Pharmacokinetic and Pharmacodynamic Properties of Drugs Considered for Testing in Human Efficacy Trials. Clin Pharmacokinet. 2016 Aug;55(8):907-23. doi: 10.1007/s40262-015-0364-1. [Article]
- Nguyen TH, Guedj J, Anglaret X, Laouenan C, Madelain V, Taburet AM, Baize S, Sissoko D, Pastorino B, Rodallec A, Piorkowski G, Carazo S, Conde MN, Gala JL, Bore JA, Carbonnelle C, Jacquot F, Raoul H, Malvy D, de Lamballerie X, Mentre F: Favipiravir pharmacokinetics in Ebola-Infected patients of the JIKI trial reveals concentrations lower than targeted. PLoS Negl Trop Dis. 2017 Feb 23;11(2):e0005389. doi: 10.1371/journal.pntd.0005389. eCollection 2017 Feb. [Article]
- de Farias ST, Dos Santos Junior AP, Rego TG, Jose MV: Origin and Evolution of RNA-Dependent RNA Polymerase. Front Genet. 2017 Sep 20;8:125. doi: 10.3389/fgene.2017.00125. eCollection 2017. [Article]
- Shu B, Gong P: Structural basis of viral RNA-dependent RNA polymerase catalysis and translocation. Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):E4005-14. doi: 10.1073/pnas.1602591113. Epub 2016 Jun 23. [Article]
- Nagata T, Lefor AK, Hasegawa M, Ishii M: Favipiravir: a new medication for the Ebola virus disease pandemic. Disaster Med Public Health Prep. 2015 Feb;9(1):79-81. doi: 10.1017/dmp.2014.151. Epub 2014 Dec 29. [Article]
- Rosenke K, Feldmann H, Westover JB, Hanley PW, Martellaro C, Feldmann F, Saturday G, Lovaglio J, Scott DP, Furuta Y, Komeno T, Gowen BB, Safronetz D: Use of Favipiravir to Treat Lassa Virus Infection in Macaques. Emerg Infect Dis. 2018 Sep;24(9):1696-1699. doi: 10.3201/eid2409.180233. Epub 2018 Sep 17. [Article]
- Delang L, Abdelnabi R, Neyts J: Favipiravir as a potential countermeasure against neglected and emerging RNA viruses. Antiviral Res. 2018 May;153:85-94. doi: 10.1016/j.antiviral.2018.03.003. Epub 2018 Mar 7. [Article]
- Nature Biotechnology: Coronavirus puts drug repurposing on the fast track [Link]
- Pharmaceuticals and Medical Devices Agency: Avigan (favipiravir) Review Report [Link]
- World Health Organization: Influenza (Avian and other zoonotic) [Link]
- External Links
- PubChem Compound
- 492405
- PubChem Substance
- 347828705
- ChemSpider
- 431002
- BindingDB
- 429507
- ChEBI
- 134722
- ChEMBL
- CHEMBL221722
- ZINC
- ZINC000013915654
- Wikipedia
- Favipiravir
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Clinical Manifestation of COVID-19 / Coronavirus Disease 2019 (COVID‑19) / Duration of Hospitalization 1 somestatus stop reason just information to hide Not Available Completed Not Available Complications of Medical Care / Coronavirus Disease 2019 (COVID‑19) / Viral Pneumonia 1 somestatus stop reason just information to hide Not Available Completed Treatment Coronavirus Disease 2019 (COVID‑19) 1 somestatus stop reason just information to hide Not Available Completed Treatment Coronavirus Disease 2019 (COVID‑19) / Favipiravir (Favipira) / Hydroxychloroquine / Kaletra / Lopinavir/Ritonavir 1 somestatus stop reason just information to hide Not Available Unknown Status Not Available Coronavirus Disease 2019 (COVID‑19) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 200.00 mg Tablet, film coated Oral 200 mg Tablet Oral 200 mg Tablet, film coated Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 187℃ to 193℃ https://www.pmda.go.jp/files/000210319.pdf water solubility slightly soluble in water https://www.pmda.go.jp/files/000210319.pdf pKa 5.1 https://www.pmda.go.jp/files/000210319.pdf - Predicted Properties
Property Value Source Water Solubility 8.7 mg/mL ALOGPS logP 0.49 ALOGPS logP 0.25 Chemaxon logS -1.3 ALOGPS pKa (Strongest Acidic) 9.39 Chemaxon pKa (Strongest Basic) -3.7 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 89.1 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 33.98 m3·mol-1 Chemaxon Polarizability 12.12 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0a4l-9700000000-8e6268a2a95cda13e7b1 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0900000000-16565f6b64e961605bc9 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0bt9-0900000000-3c08dbf0418b290a578c Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-00kf-0900000000-c30fff122d0f778e5d46 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-02mr-9400000000-985d584fb66033021e32 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-052v-9000000000-fa31ce96a20f7c3e423e Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-9000000000-3f236023add364067245 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 130.38437 predictedDeepCCS 1.0 (2019) [M+H]+ 132.78401 predictedDeepCCS 1.0 (2019) [M+Na]+ 141.31496 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
- Pharmacological action
- Yes
- Actions
- Modulator
- General Function
- DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
- Specific Function
- DNA binding
- Gene Name
- rpoB
- Uniprot ID
- P9WGY9
- Uniprot Name
- DNA-directed RNA polymerase subunit beta
- Molecular Weight
- 129863.895 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Mycobacterium tuberculosis
- Pharmacological action
- Yes
- Actions
- Modulator
- General Function
- DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
- Specific Function
- DNA binding
- Gene Name
- rpoC
- Uniprot ID
- P9WGY7
- Uniprot Name
- DNA-directed RNA polymerase subunit beta'
- Molecular Weight
- 146768.085 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Influenza A virus (strain A/Silky Chicken/Hong Kong/SF189/2001 H5N1 genotype A)
- Pharmacological action
- Yes
- General Function
- RNA-dependent RNA polymerase which is responsible for replication and transcription of virus RNA segments. The transcription of viral mRNAs occurs by a unique mechanism called cap-snatching. 5' methylated caps of cellular mRNAs are cleaved after 10-13 nucleotides by PA. In turn, these short capped RNAs are used as primers by PB1 for transcription of viral mRNAs. During virus replication, PB1 initiates RNA synthesis and copy vRNA into complementary RNA (cRNA) which in turn serves as a template for the production of more vRNAs.
- Specific Function
- nucleotide binding
- Gene Name
- PB1
- Uniprot ID
- Q809M3
- Uniprot Name
- RNA-directed RNA polymerase catalytic subunit
- Molecular Weight
- 86420.48 Da
References
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- General Function
- Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide, N-methylphthalazinium and phthalazine, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir, which is a potent antiviral agent. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. May also catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. May play a role in adipogenesis
- Specific Function
- 2 iron, 2 sulfur cluster binding
- Gene Name
- AOX1
- Uniprot ID
- Q06278
- Uniprot Name
- Aldehyde oxidase
- Molecular Weight
- 147916.735 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro)
- Specific Function
- 2 iron, 2 sulfur cluster binding
- Gene Name
- XDH
- Uniprot ID
- P47989
- Uniprot Name
- Xanthine dehydrogenase/oxidase
- Molecular Weight
- 146422.99 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- CYP2E1 is inhibited by favipiravir's major metabolite.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
- Specific Function
- 4-nitrophenol 2-monooxygenase activity
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Pharmaceuticals and Medical Devices Agency: Avigan (favipiravir) Review Report [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Carrier
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Pharmaceuticals and Medical Devices Agency: Avigan (favipiravir) Review Report [Link]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Carrier
- General Function
- Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
- Specific Function
- Not Available
Components:
References
- Pharmaceuticals and Medical Devices Agency: Avigan (favipiravir) Review Report [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Pharmaceuticals and Medical Devices Agency: Avigan (favipiravir) Review Report [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
- Specific Function
- alpha-ketoglutarate transmembrane transporter activity
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- Pharmaceuticals and Medical Devices Agency: Avigan (favipiravir) Review Report [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
- Specific Function
- organic anion transmembrane transporter activity
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Organic anion transporter 3
- Molecular Weight
- 59855.585 Da
References
- Pharmaceuticals and Medical Devices Agency: Avigan (favipiravir) Review Report [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Electroneutral antiporter that translocates urate across the apical membrane of proximal tubular cells in exchange for monovalent organic or inorganic anions (PubMed:12024214, PubMed:22194875, PubMed:35144162, PubMed:35462902). Involved in renal reabsorption of urate and helps maintaining blood levels of uric acid (PubMed:12024214, PubMed:22194875). Mediates urate uptake by an exchange with organic anions such as (S)-lactate and nicotinate, and inorganic anion Cl(-) (PubMed:12024214). Other inorganic anions such as Br(-), I(-) and NO3(-) may also act as counteranions that exchange for urate (PubMed:12024214). Also mediates orotate tubular uptake coupled with nicotinate efflux and to a lesser extent with lactate efflux, therefore displaying a potential role in orotate renal reabsorption (PubMed:21350910). Orotate transport is Cl(-)-dependent (PubMed:21350910)
- Specific Function
- PDZ domain binding
- Gene Name
- SLC22A12
- Uniprot ID
- Q96S37
- Uniprot Name
- Solute carrier family 22 member 12
- Molecular Weight
- 59629.57 Da
References
- Pharmaceuticals and Medical Devices Agency: Avigan (favipiravir) Review Report [Link]
Drug created at October 20, 2016 22:30 / Updated at August 26, 2024 19:23