Ombitasvir
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Identification
- Summary
Ombitasvir is a direct acting antiviral agent used in combination with other antiviral agents for the treatment of Hepatitis C Virus (HCV) infections.
- Brand Names
- Viekira Pak
- Generic Name
- Ombitasvir
- DrugBank Accession Number
- DB09296
- Background
Ombitasvir 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 Ombitasvir. Ombitasvir is an inhibitor of NS5A, a protein essential for viral replication and virion assembly Label. The barrier for develoment of resistance to NS5A inhibitors is lower than that of NS5B inhibitors, another class of DAAs 5.
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 Ombitasvir as a first line therapy option when used in combination with other antivirals for genotypes 1a, 1b, and 4 8. Depending on the genotype, Ombitasvir is often used in combination with other antivirals such as Dasabuvir, Paritaprevir, Ritonavir, and Ribavirin with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily 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 6. Treatment with direct acting antivirals such as Ombitasvir is associated with very minimal side effects, with the most common being headache and fatigue Label. Lack of significant side effects and short duration of therapy is a considerable advantage over older interferon-based regimens, which were limited by infusion site reactions, reduced blood count, and neuropsychiatric effects 7.
Ombutasvir first came on the market as a fixed-dose combination product with Dasabuvir, Paritaprevir, and Ritonavir as the FDA-approved product Viekira Pak. First approved in December 2014, Viekira Pak is indicated for the treatment of HCV genotype 1b without cirrhosis or with compensated cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a without cirrhosis or with compensated cirrhosis.
Ombutasvir is also available as a fixed-dose combination product with Paritaprevir and Ritonavir as the FDA- and Health Canada-approved product Technivie. First approved in July 2015, Technivie is indicated in combination with Ribavirin for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis.
In Canada, Ombutasvir is also available as a fixed-dose combination product with Dasabuvir, Paritaprevir, and Ritonavir as the Health Canada-approved, commercially available product Holkira Pak. First approved in January 2015, Holkira Pak is indicated for the treatment of HCV genotype 1b with or without cirrhosis, and when combined with Ribavirin for the treatment of HCV genotype 1a with or without cirrhosis.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 894.127
Monoisotopic: 893.505112145 - Chemical Formula
- C50H67N7O8
- Synonyms
- dimethyl ([(2S,5S)-1-(4-tert-butylphenyl)pyrrolidine-2,5-diyl]bis{(4,1-phenylene)carbamoyl(2S)pyrrolidine-2,1-diyl[(2S)-3-methyl-1-oxobutane-1,2-diyl]})biscarbamate
- Ombitasvir
- External IDs
- ABT 267
- ABT-267
- ABT267
Pharmacology
- Indication
When used in combination with Paritaprevir and Ritonavir (as the fixed dose product Technivie), Ombitasvir is indicated in combination with Ribavirin for the treatment of patients with genotype 4 chronic hepatitis C virus (HCV) infection without cirrhosis 9.
When used in combination with Paritaprevir, Ritonavir, and Dasabuvir (as the fixed dose product Viekira Pak), Ombitasvir is indicated for the treatment of HCV genotype 1b and ,when combined with Ribavirin, for the treatment of HCV genotype 1a 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: Dasabuvir (DB09183), Paritaprevir (DB09297), Ritonavir (DB00503), Ribavirin (DB00811) •••••••••••• Used in combination to treat Chronic hepatitis c genotype 1b Combination Product in combination with: Ritonavir (DB00503), Dasabuvir (DB09183), Paritaprevir (DB09297) •••••••••••• Used in combination to treat Without cirrhosis chronic hepatitis c genotype 4 Regimen in combination with: Paritaprevir (DB09297), Ritonavir (DB00503), Ribavirin (DB00811) •••••••••••• - 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
Ombitasvir is classified as a direct acting antiviral and acts against HCV to inhibit viral replication Label.
- Mechanism of action
Ombitasvir is an inhibitor of the HCV non-structural protein 5A. While the precise role of this protein is unknown, it is essential to viral replication and virion assembly Label. Potential modes of action of NS5A inhibitors like Elbasvir include blocking signaling interactions, redistribution of NS5A from the endoplasmic reticulum to the surface of lipid droplets, and modification of the HCV replication complex 5.
Target Actions Organism ANonstructural protein 5A inhibitorHepatitis C Virus AGenome polyprotein modulator- Absorption
Ombitasvir reaches peak plasma concentration 5 hours after administration Label. It has an absolute bioavailability of 48%. Taking ombitasvir with high or normal fat meals increases exposure by 1.76 or 1.82 fold respectively.
- Volume of distribution
Ombitasvir has a volume of distribution at steady state of 173 liters Label.
- Protein binding
Ombitasvir is 99.9% bound to human plasma proteins Label.
- Metabolism
Ombitasvir is mainly metabolized by amide hydrolysis followed by CYP2C8-mediated oxidative metabolism Label.
- Route of elimination
Ombitasvir is mainly excreted in the feces (90.2%) with very little excreted in the urine (1.91%) Label. 87.8% and 0.03% of the dose excreted in the feces and urine respectively is present as the parent compound.
- Half-life
Ombitasvir has a half life of elimination of 21-25 hours Label
- Clearance
Clearance of Ombitasvir 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. The most common adverse effects of Technivie with or without Ribavirin were asthenia, fatigue, nausea, insomnia and pruritus 9.
- 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 Ombitasvir. Abatacept The metabolism of Ombitasvir can be increased when combined with Abatacept. Abemaciclib Abemaciclib may decrease the excretion rate of Ombitasvir which could result in a higher serum level. Abiraterone The metabolism of Ombitasvir can be decreased when combined with Abiraterone. Abrocitinib The serum concentration of Ombitasvir can be increased when it is combined with Abrocitinib. - Food Interactions
- Avoid St. John's Wort.
- 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 Ombitasvir heminonahydrate EQE3I70J3W 1456607-70-7 AWMWWEBJJCSJHI-MVJJBPFMSA-N - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Holkira Pak Ombitasvir (12.5 mg) + Dasabuvir sodium monohydrate (250 mg) + Paritaprevir (75 mg) + Ritonavir (50 mg) Kit; Tablet Oral Abbvie 2015-01-06 2018-08-15 Canada Technivie Ombitasvir (12.5 mg) + Paritaprevir (75 mg) + Ritonavir (50 mg) Tablet Oral Abbvie 2015-11-24 2018-07-30 Canada Technivie Ombitasvir heminonahydrate (12.5 mg/1) + Paritaprevir dihydrate (75 mg/1) + Ritonavir (50 mg/1) Tablet Oral Abbvie 2015-07-24 2019-03-14 US Viekira Pak Ombitasvir heminonahydrate (12.5 mg/1) + Dasabuvir sodium monohydrate (250 mg/1) + Paritaprevir dihydrate (75 mg/1) + Ritonavir (50 mg/1) Kit; Tablet, film coated Oral Abbvie 2014-12-19 Not applicable US VIEKIRA PAK TABLET Ombitasvir (12.5 mg) + Dasabuvir (250 mg) + Paritaprevir (75 mg) + Ritonavir (50 mg) Tablet, film coated Oral Abbvie 2015-11-02 Not applicable Singapore
Categories
- ATC Codes
- J05AP53 — Ombitasvir, paritaprevir and ritonavir
- 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
- Amino Acids
- Amino Acids, Branched-Chain
- Amino Acids, Cyclic
- Amino Acids, Essential
- Amino Acids, Peptides, and Proteins
- Aniline Compounds
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Antivirals for treatment of HCV infections
- BCRP/ABCG2 Substrates
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 Substrates
- Direct Acting Antivirals
- Hepatitis C Virus NS5A Inhibitor
- Imino Acids
- P-glycoprotein substrates
- Treatments for Hepatitis C
- UGT1A1 Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Dipeptides
- Alternative Parents
- Valine and derivatives / Proline and derivatives / Alpha amino acid amides / Phenylpyrrolidines / Phenylpropanes / Anilides / Pyrrolidinecarboxamides / Aniline and substituted anilines / N-arylamides / N-acylpyrrolidines show 12 more
- Substituents
- 1-phenylpyrrolidine / 2-phenylpyrrolidine / Alpha-amino acid amide / Alpha-amino acid or derivatives / Alpha-dipeptide / Amine / Amino acid or derivatives / Anilide / Aniline or substituted anilines / Aralkylamine show 31 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- carbamate ester, dipeptide, pyrrolidines, ring assembly, aromatic amide (CHEBI:85183)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 2302768XJ8
- CAS number
- 1258226-87-7
- InChI Key
- PIDFDZJZLOTZTM-KHVQSSSXSA-N
- InChI
- InChI=1S/C50H67N7O8/c1-30(2)42(53-48(62)64-8)46(60)55-28-10-12-40(55)44(58)51-35-20-14-32(15-21-35)38-26-27-39(57(38)37-24-18-34(19-25-37)50(5,6)7)33-16-22-36(23-17-33)52-45(59)41-13-11-29-56(41)47(61)43(31(3)4)54-49(63)65-9/h14-25,30-31,38-43H,10-13,26-29H2,1-9H3,(H,51,58)(H,52,59)(H,53,62)(H,54,63)/t38-,39-,40-,41-,42-,43-/m0/s1
- IUPAC Name
- methyl N-[(2S)-1-[(2S)-2-({4-[(2S,5S)-1-(4-tert-butylphenyl)-5-{4-[(2S)-1-[(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl]pyrrolidine-2-amido]phenyl}pyrrolidin-2-yl]phenyl}carbamoyl)pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
- SMILES
- COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C(C=C1)[C@@H]1CC[C@H](N1C1=CC=C(C=C1)C(C)(C)C)C1=CC=C(NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)OC)C(C)C)C=C1
References
- General References
- Shen J, Serby M, Surber B, Lee AJ, Ma J, Badri P, Menon R, Kavetskaia O, de Morais SM, Sydor J, Fischer V: Metabolism and Disposition of Pan-Genotypic Inhibitor of Hepatitis C Virus NS5A Ombitasvir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1148-57. doi: 10.1124/dmd.115.067496. Epub 2016 May 13. [Article]
- DeGoey DA, Randolph JT, Liu D, Pratt J, Hutchins C, Donner P, Krueger AC, Matulenko M, Patel S, Motter CE, Nelson L, Keddy R, Tufano M, Caspi DD, Krishnan P, Mistry N, Koev G, Reisch TJ, Mondal R, Pilot-Matias T, Gao Y, Beno DW, Maring CJ, Molla A, Dumas E, Campbell A, Williams L, Collins C, Wagner R, Kati WM: Discovery of ABT-267, a pan-genotypic inhibitor of HCV NS5A. J Med Chem. 2014 Mar 13;57(5):2047-57. doi: 10.1021/jm401398x. Epub 2014 Jan 15. [Article]
- Keating GM: Ombitasvir/Paritaprevir/Ritonavir: A Review in Chronic HCV Genotype 4 Infection. Drugs. 2016 Aug;76(12):1203-11. doi: 10.1007/s40265-016-0612-1. [Article]
- Macdonald A, Harris M: Hepatitis C virus NS5A: tales of a promiscuous protein. J Gen Virol. 2004 Sep;85(Pt 9):2485-502. [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]
- Dusheiko G: Side effects of alpha interferon in chronic hepatitis C. Hepatology. 1997 Sep;26(3 Suppl 1):112S-121S. [Article]
- American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
- Dailymed: Technivie [Link]
- External Links
- KEGG Drug
- D10745
- PubChem Compound
- 54767916
- PubChem Substance
- 310265188
- ChemSpider
- 31136214
- BindingDB
- 50453112
- 1597371
- ChEBI
- 85183
- ChEMBL
- CHEMBL3127326
- ZINC
- ZINC000150601177
- PharmGKB
- PA166163409
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Ombitasvir
- 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 Oral Kit; tablet, film coated Oral Tablet, film coated Oral 250 mg Kit; tablet Oral Tablet, film coated Oral Tablet, coated 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 0.00193 mg/mL ALOGPS logP 5.72 ALOGPS logP 7.49 Chemaxon logS -5.7 ALOGPS pKa (Strongest Acidic) 12.77 Chemaxon pKa (Strongest Basic) 2.16 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 178.72 Å2 Chemaxon Rotatable Bond Count 16 Chemaxon Refractivity 250.79 m3·mol-1 Chemaxon Polarizability 99.1 Å3 Chemaxon Number of Rings 6 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 301.35345 predictedDeepCCS 1.0 (2019) [M+H]+ 303.07718 predictedDeepCCS 1.0 (2019) [M+Na]+ 309.40616 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Hepatitis C Virus
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- cysteine-type endopeptidase activity
- Gene Name
- NS5A
- Uniprot ID
- Q5L478
- Uniprot Name
- Nonstructural protein 5A
- Molecular Weight
- 48598.34 Da
References
- DeGoey DA, Randolph JT, Liu D, Pratt J, Hutchins C, Donner P, Krueger AC, Matulenko M, Patel S, Motter CE, Nelson L, Keddy R, Tufano M, Caspi DD, Krishnan P, Mistry N, Koev G, Reisch TJ, Mondal R, Pilot-Matias T, Gao Y, Beno DW, Maring CJ, Molla A, Dumas E, Campbell A, Williams L, Collins C, Wagner R, Kati WM: Discovery of ABT-267, a pan-genotypic inhibitor of HCV NS5A. J Med Chem. 2014 Mar 13;57(5):2047-57. doi: 10.1021/jm401398x. Epub 2014 Jan 15. [Article]
- Kind
- Protein
- Organism
- Not Available
- Pharmacological action
- Yes
- Actions
- Modulator
- General Function
- Mature core protein Packages viral RNA to form a viral nucleocapsid, and promotes virion budding (Probable). Participates in the viral particle production as a result of its interaction with the non-structural protein 5A (By similarity). Binds RNA and may function as a RNA chaperone to induce the RNA structural rearrangements taking place during virus replication (By similarity). Modulates viral translation initiation by interacting with viral IRES and 40S ribosomal subunit (By similarity). Affects various cell signaling pathways, host immunity and lipid metabolism (Probable). Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by blocking the formation of phosphorylated STAT1 and promoting ubiquitin-mediated proteasome-dependent degradation of STAT1 (By similarity). Activates STAT3 leading to cellular transformation (By similarity). Regulates the activity of cellular genes, including c-myc and c-fos (PubMed:8533458). May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm (PubMed:9110985). Represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation (PubMed:9524287). Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses TNF-induced NF-kappa-B activation, and activates AP-1 (PubMed:9811706). Binds to dendritic cells (DCs) via C1QR1, resulting in down-regulation of T-lymphocytes proliferation (By similarity). Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage (By similarity). Induces up-regulation of FAS promoter activity, and thereby contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity).
- Specific Function
- ATP binding
- 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]
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, Surber B, Lee AJ, Ma J, Badri P, Menon R, Kavetskaia O, de Morais SM, Sydor J, Fischer V: Metabolism and Disposition of Pan-Genotypic Inhibitor of Hepatitis C Virus NS5A Ombitasvir in Humans. Drug Metab Dispos. 2016 Aug;44(8):1148-57. doi: 10.1124/dmd.115.067496. 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
References
- Keating GM: Ombitasvir/Paritaprevir/Ritonavir: A Review in Chronic HCV Genotype 4 Infection. Drugs. 2016 Aug;76(12):1203-11. doi: 10.1007/s40265-016-0612-1. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
References
- Keating GM: Ombitasvir/Paritaprevir/Ritonavir: A Review in Chronic HCV Genotype 4 Infection. Drugs. 2016 Aug;76(12):1203-11. doi: 10.1007/s40265-016-0612-1. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- 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
Drug created at October 30, 2015 15:54 / Updated at August 26, 2024 19:23