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Identification
- Summary
Dasabuvir is a direct-acting antiviral agent used to treat specific hepatitis C virus (HCV) infections in combination with other antiviral agents.
- Brand Names
- Exviera, Viekira Pak
- Generic Name
- Dasabuvir
- DrugBank Accession Number
- DB09183
- Background
Dasabuvir is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients 8. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as Dasabuvir. Dasabuvir is a non-nucleoside NS5B inhibitor which binds to the palm domain of NS5B and induces a conformational change which renders the polymerase unable to elongate viral RNA Label. The binding sites for non-nucleoside NS5B inhibitors are poorly conserved across HCV genotypes leading to the restriction of Dasabuvir's use to genotype 1 only.
In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Dasabuvir as first line therapy in combination with Ombitasvir, Paritaprevir, and Ritonavir for genotype 1b and with Ribavirin for genotype 1a of Hepatitis C 8. Dasabuvir, Ombitasvir, Paritaprevir, Ritonavir, and Ribavirin are used with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality 7.
Dasabuvir is available as a fixed dose combination product with Ombitasvir, Paritaprevir, and Ritonavir (tradename Viekira Pak) used for the treatment of chronic Hepatitis C. Approved in December 2014 by the FDA, Viekira Pak is indicated for the treatment of HCV genotype 1a with Ribavirin or genotype 1b without Ribavirin Label. When combined together, Dasabuvir Ombitasvir, Paritaprevir, and Ritonavir as the combination product Viekira Pak have been shown to achieve a SVR of 100% for genotype 1b and 89% or 95% for genotype 1a after 12 weeks or 24 weeks of treatment including Ribavirin.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Dasabuvir (DB09183)
- Weight
- Average: 493.58
Monoisotopic: 493.167142155 - Chemical Formula
- C26H27N3O5S
- Synonyms
- Sodium 3-(3-tert-butyl-4-methoxy-5-{6 [(methylsulfonyl)amino]naphthalene-2-yl}phenyl)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-ide hydrate (1:1:1)
- Dasabuvir
- N-{6-[3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl]naphthalen-2-yl}methanesulfonamide
- External IDs
- ABT 333
- ABT-333
- ABT333
Pharmacology
- Indication
Dasabuvir, in combination with Ombitasvir, Paritaprevir, and Ritonavir (as Viekira Pak) is indicated for the treatment of patients with HCV genotype 1a with Ribavirin or genotype 1b without Ribavirin including those with compensated cirrhosis Label.
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 Used in combination to treat Chronic hepatitis c genotype 1a Regimen in combination with: Ribavirin (DB00811), Paritaprevir (DB09297), Ritonavir (DB00503), Ombitasvir (DB09296) •••••••••••• Used in combination to treat Chronic hepatitis c genotype 1b Combination Product in combination with: Paritaprevir (DB09297), Ritonavir (DB00503), Ombitasvir (DB09296) •••••••••••• - Contraindications & Blackbox Warnings
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Dasabuvir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotype 1 Label.
- Mechanism of action
Dasabuvir is a non-nucleoside inhibitor of the HCV RNA-dependent RNA polymerase encoded by the NS5B gene, which is essential for replication of the viral genome Label. Based on drug resistance mapping studies of HCV genotypes 1a and 1b, dasabuvir targets the palm domain of the NS5B polymerase, and is therefore referred to as a non-nucleoside NS5B-palm polymerase inhibitor. The EC50 values of dasabuvir against genotype 1a-H77 and 1b-Con1 strains in HCV replicon cell culture assays were 7.7 nM and 1.8 nM, respectively.
By binding to NS5b outside of the active site of the enzyme, dasabuvir induces a conformational change thereby preventing further elongation of the nascent viral genome 6,Label. A limitation of binding outside of the active site is that these binding sites are poorly preserved across the viral genotypes. This results in a limited potential for cross-genotypic activity and increased potential for development of resistance. Dasabuvir is therefore limited to treating genotypes 1a and 1b, and must be used in combination with other antiviral products.
Target Actions Organism AGenome polyprotein inhibitorANonstructural protein 5b inhibitor- Absorption
Dasabuvir reaches peak plasma concentration 4 hours after administration Label. The absolute bioavailability of Dasabuvir is 70%.
- Volume of distribution
Dasabuvir has a volume of distribution at steady state of 149 liters Label.
- Protein binding
Dasabuvir is greater than 99.5% bound to human plasma proteins Label.
- Metabolism
Dasabuvir is predominantly metabolized by CYP2C8, and to a lesser extent by CYP3A Label.
- Route of elimination
Dasabuvir is mainly excreted in the feces (94.4%) with very little excreted in the urine (2%) Label. 26.2% and 0.03% of the drug excreted in the feces and urine respectively was present as the parent compound suggesting metabolism as the major elimination pathway.
- Half-life
The half-life of elimination of dasabuvir is 5.5 to 6 hours Label.
- Clearance
Clearance of Dasabuvir has not been determined.
- 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
The most common adverse effects of Viekira Pak either in combination with or without Ribavirin were pruritus, nausea, insomnia, and asthenia Label.
- 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 softwareAbacavir The metabolism of Abacavir can be decreased when combined with Dasabuvir. Abametapir The serum concentration of Dasabuvir can be increased when it is combined with Abametapir. Abatacept The metabolism of Dasabuvir can be increased when combined with Abatacept. Abemaciclib Dasabuvir may decrease the excretion rate of Abemaciclib which could result in a higher serum level. Abiraterone The metabolism of Dasabuvir can be decreased when combined with Abiraterone. - Food Interactions
- Avoid St. John's Wort. This herb induces the CYP3A metabolism of dasabuvir and may reduce its serum concentration. St. John's Wort is contraindicated for use with Viekira Pak.
- Take at the same time every day.
- Take with food.
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.- Product Ingredients
Ingredient UNII CAS InChI Key Dasabuvir sodium R2M8F5TK9T 1132940-11-4 XHGMJAKIIJSQMF-UHFFFAOYSA-M Dasabuvir sodium monohydrate OG6D40M62L 1456607-55-8 SJHKKWUESHNTBB-UHFFFAOYSA-M - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Exviera Tablet, film coated 250 mg Oral Abb Vie Deutschland Gmb H & Co. Kg 2016-09-08 Not applicable EU 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Holkira Pak Dasabuvir sodium monohydrate (250 mg) + Ombitasvir (12.5 mg) + Paritaprevir (75 mg) + Ritonavir (50 mg) Kit; Tablet Oral Abbvie 2015-01-06 2018-08-15 Canada 
Viekira Pak Dasabuvir sodium monohydrate (250 mg/1) + Ombitasvir heminonahydrate (12.5 mg/1) + Paritaprevir dihydrate (75 mg/1) + Ritonavir (50 mg/1) Kit; Tablet, film coated Oral AbbVie Inc. 2014-12-19 Not applicable US 
VIEKIRA PAK TABLET Dasabuvir (250 mg) + Ombitasvir (12.5 mg) + Paritaprevir (75 mg) + Ritonavir (50 mg) Tablet, film coated Oral ABBVIE PTE. LTD. 2015-11-02 Not applicable Singapore 
Viekira XR Dasabuvir sodium monohydrate (200 mg/1) + Ombitasvir heminonahydrate (8.33 mg/1) + Paritaprevir dihydrate (50 mg/1) + Ritonavir (33.33 mg/1) Kit; Tablet Oral AbbVie Inc. 2016-07-22 2019-01-17 US
Categories
- ATC Codes
- J05AP09 — Dasabuvir
- J05AP — Antivirals for treatment of HCV infections
- J05A — DIRECT ACTING ANTIVIRALS
- J05 — ANTIVIRALS FOR SYSTEMIC USE
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- Drug Categories
- Amides
- Amines
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Antivirals for treatment of HCV infections
- BCRP/ABCG2 Inhibitors
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Direct Acting Antivirals
- Hepatitis C Virus Non-Nucleoside NS5B Palm Polymerase Inhibitor
- Naphthalenes
- P-glycoprotein substrates
- Pyrimidines
- Pyrimidinones
- RNA Replicase Inhibitors
- Sulfones
- Sulfur Compounds
- Treatments for Hepatitis C
- UGT1A1 Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylnaphthalenes. These are compounds containing a phenylnaphthalene skeleton, which consists of a naphthalene bound to a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Naphthalenes
- Sub Class
- Phenylnaphthalenes
- Direct Parent
- Phenylnaphthalenes
- Alternative Parents
- Sulfanilides / Methoxyanilines / Phenylpropanes / Phenoxy compounds / Anisoles / Methoxybenzenes / Pyrimidones / Alkyl aryl ethers / Organosulfonamides / Organic sulfonamides show 11 more
- Substituents
- Alkyl aryl ether / Aminosulfonyl compound / Anisole / Aromatic heteropolycyclic compound / Azacycle / Ether / Heteroaromatic compound / Hydrocarbon derivative / Hydropyrimidine / Lactam show 25 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- aromatic ether, sulfonamide, pyrimidone, ring assembly, naphthalenes (CHEBI:85182)
- Affected organisms
- Hepatitis C Virus
Chemical Identifiers
- UNII
- DE54EQW8T1
- CAS number
- 1132935-63-7
- InChI Key
- NBRBXGKOEOGLOI-UHFFFAOYSA-N
- InChI
- InChI=1S/C26H27N3O5S/c1-26(2,3)22-15-20(29-11-10-23(30)27-25(29)31)14-21(24(22)34-4)18-7-6-17-13-19(28-35(5,32)33)9-8-16(17)12-18/h6-15,28H,1-5H3,(H,27,30,31)
- IUPAC Name
- N-{6-[3-tert-butyl-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-2-methoxyphenyl]naphthalen-2-yl}methanesulfonamide
- SMILES
- COC1=C(C=C(C=C1C1=CC2=CC=C(NS(C)(=O)=O)C=C2C=C1)N1C=CC(=O)NC1=O)C(C)(C)C
References
- General References
- Gentile I, Buonomo AR, Borgia G: Dasabuvir: A Non-Nucleoside Inhibitor of NS5B for the Treatment of Hepatitis C Virus Infection. Rev Recent Clin Trials. 2014;9(2):115-23. [Article]
- Trivella JP, Gutierrez J, Martin P: Dasabuvir : a new direct antiviral agent for the treatment of hepatitis C. Expert Opin Pharmacother. 2015 Mar;16(4):617-24. doi: 10.1517/14656566.2015.1012493. Epub 2015 Feb 9. [Article]
- Mantry PS, Pathak L: Dasabuvir (ABT333) for the treatment of chronic HCV genotype I: a new face of cure, an expert review. Expert Rev Anti Infect Ther. 2016 Feb;14(2):157-65. doi: 10.1586/14787210.2016.1120668. Epub 2015 Dec 17. [Article]
- McConachie SM, Wilhelm SM, Kale-Pradhan PB: New direct-acting antivirals in hepatitis C therapy: a review of sofosbuvir, ledipasvir, daclatasvir, simeprevir, paritaprevir, ombitasvir and dasabuvir. Expert Rev Clin Pharmacol. 2016 Feb;9(2):287-302. doi: 10.1586/17512433.2016.1129272. Epub 2016 Jan 8. [Article]
- Shen J, Serby M, Reed A, Lee AJ, Menon R, Zhang X, Marsh K, Wan X, Kavetskaia O, Fischer V: Metabolism and Disposition of Hepatitis C Polymerase Inhibitor Dasabuvir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1139-47. doi: 10.1124/dmd.115.067512. Epub 2016 May 13. [Article]
- Bagaglio S, Uberti-Foppa C, Morsica G: Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use. Drugs. 2017 May 12. doi: 10.1007/s40265-017-0753-x. [Article]
- Myers RP, Shah H, Burak KW, Cooper C, Feld JJ: An update on the management of chronic hepatitis C: 2015 Consensus guidelines from the Canadian Association for the Study of the Liver. Can J Gastroenterol Hepatol. 2015 Jan-Feb;29(1):19-34. Epub 2015 Jan 13. [Article]
- American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
- External Links
- KEGG Drug
- D10582
- PubChem Compound
- 56640146
- PubChem Substance
- 310265091
- ChemSpider
- 29776744
- 1597381
- ChEBI
- 85182
- ChEMBL
- CHEMBL3137312
- ZINC
- ZINC000095616937
- PharmGKB
- PA166163411
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Dasabuvir
- FDA label
- Download (540 KB)
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 Chronic Hepatitis C Virus (HCV) Infection 5 somestatus stop reason just information to hide Not Available Completed Not Available Chronic Hepatitis C Virus (HCV) Infection / Cirrhosis of the Liver 1 somestatus stop reason just information to hide Not Available Completed Not Available Chronic Hepatitis C, Genotype 1 or 4 1 somestatus stop reason just information to hide Not Available Completed Not Available Hepatitis C Infections 1 somestatus stop reason just information to hide Not Available Completed Not Available Hepatitis C Virus (HCV) Infection / Kidney Diseases 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 250 MG Kit; tablet, film coated Oral Tablet, film coated Oral 250 mg Kit; tablet Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6703403 Yes 2004-03-09 2016-12-26 US US6037157 Yes 2000-03-14 2016-12-26 US US7364752 Yes 2008-04-29 2021-05-10 US US7148359 Yes 2006-12-12 2020-01-19 US US8268349 Yes 2012-09-18 2025-02-25 US US8399015 Yes 2013-03-19 2025-02-25 US US9139536 No 2015-09-22 2028-11-09 US US8685984 No 2014-04-01 2032-09-04 US US8466159 No 2013-06-18 2032-09-04 US US8642538 No 2014-02-04 2029-09-10 US US8501238 No 2013-08-06 2028-09-17 US US8680106 No 2014-03-25 2032-09-04 US US8492386 No 2013-07-23 2032-09-04 US US8188104 No 2012-05-29 2029-05-17 US US9006387 No 2015-04-14 2030-06-10 US US9044480 No 2015-06-02 2031-04-10 US US8686026 No 2014-04-01 2031-06-09 US US8420596 Yes 2013-04-16 2031-10-10 US US8691938 No 2014-04-08 2032-04-13 US US9629841 No 2017-04-25 2033-10-18 US US9333204 No 2016-05-10 2035-01-02 US US9744170 No 2017-08-29 2035-01-02 US US10105365 No 2018-10-23 2035-01-02 US US10201584 No 2019-02-12 2032-05-17 US US10201542 No 2019-02-12 2033-10-18 US US10201541 No 2019-02-12 2032-05-17 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.000799 mg/mL ALOGPS logP 4.7 ALOGPS logP 3.42 Chemaxon logS -5.8 ALOGPS pKa (Strongest Acidic) 9.09 Chemaxon pKa (Strongest Basic) -4.8 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 104.81 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 134.04 m3·mol-1 Chemaxon Polarizability 53.19 Å3 Chemaxon Number of Rings 4 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 MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0000900000-e3fc02789acab45a1ed4 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004l-6000900000-e5f6b336b7c392c88393 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0007-1005900000-be30321ac76989053718 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00fr-4000900000-34eb46df4f1b7201bc16 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4l-0009200000-78f891cfbcfc267b77ea Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-01ox-3009400000-970b14de5640bb177160 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]- 221.93707 predictedDeepCCS 1.0 (2019) [M+H]+ 224.33263 predictedDeepCCS 1.0 (2019) [M+Na]+ 230.24516 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Not Available
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regula...
- Gene Name
- Not Available
- Uniprot ID
- P26664
- Uniprot Name
- Genome polyprotein
- Molecular Weight
- 327198.77 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
- Not Available
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- Rna binding
- Gene Name
- NS5b
- Uniprot ID
- P87764
- Uniprot Name
- Nonstructural protein 5b
- Molecular Weight
- Not Available
References
- Soriano V, Vispo E, de Mendoza C, Labarga P, Fernandez-Montero JV, Poveda E, Trevino A, Barreiro P: Hepatitis C therapy with HCV NS5B polymerase inhibitors. Expert Opin Pharmacother. 2013 Jun;14(9):1161-70. doi: 10.1517/14656566.2013.795543. Epub 2013 Apr 27. [Article]
- Mantry PS, Pathak L: Dasabuvir (ABT333) for the treatment of chronic HCV genotype I: a new face of cure, an expert review. Expert Rev Anti Infect Ther. 2016 Feb;14(2):157-65. doi: 10.1586/14787210.2016.1120668. Epub 2015 Dec 17. [Article]
- Trivella JP, Gutierrez J, Martin P: Dasabuvir : a new direct antiviral agent for the treatment of hepatitis C. Expert Opin Pharmacother. 2015 Mar;16(4):617-24. doi: 10.1517/14656566.2015.1012493. Epub 2015 Feb 9. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- 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
- Shen J, Serby M, Reed A, Lee AJ, Menon R, Zhang X, Marsh K, Wan X, Kavetskaia O, Fischer V: Metabolism and Disposition of Hepatitis C Polymerase Inhibitor Dasabuvir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1139-47. doi: 10.1124/dmd.115.067512. Epub 2016 May 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). 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). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Shen J, Serby M, Reed A, Lee AJ, Menon R, Zhang X, Marsh K, Wan X, Kavetskaia O, Fischer V: Metabolism and Disposition of Hepatitis C Polymerase Inhibitor Dasabuvir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1139-47. doi: 10.1124/dmd.115.067512. Epub 2016 May 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). 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:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- Anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Shen J, Serby M, Reed A, Lee AJ, Menon R, Zhang X, Marsh K, Wan X, Kavetskaia O, Fischer V: Metabolism and Disposition of Hepatitis C Polymerase Inhibitor Dasabuvir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1139-47. doi: 10.1124/dmd.115.067512. Epub 2016 May 13. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808, PubMed:24525562). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558)
- Specific Function
- Enzyme binding
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1A1
- Molecular Weight
- 59590.91 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- Abc-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Energy-dependent efflux transporter responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:12960149, PubMed:15205344, PubMed:15899824, PubMed:22306008). Specifically present in limbal stem cells, where it plays a key role in corneal development and repair (By similarity)
- Specific Function
- Abc-type xenobiotic transporter activity
- Gene Name
- ABCB5
- Uniprot ID
- Q2M3G0
- Uniprot Name
- ATP-binding cassette sub-family B member 5
- Molecular Weight
- 138639.48 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
Drug created at October 15, 2015 18:45 / Updated at September 15, 2024 21:28