Explore a selection of our essential drug information below, or:
Identification
- Summary
Telaprevir is an NS3/4A viral protease inhibitor used in combination with other antivirals for the curative treatment of chronic Hepatitis C Virus infections.
- Generic Name
- Telaprevir
- DrugBank Accession Number
- DB05521
- Background
Telaprevir 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 7. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as Telaprevir. Telaprevir is an inhibitor of NS3/4A, a serine protease enzyme, encoded by HCV genotype 1 Label. These enzymes are essential for viral replication and serve to cleave the virally encoded polyprotein into mature proteins like NS4A, NS4B, NS5A and NS5B. The barrier for develoment of resistance to NS3/4A inhibitors is lower than that of NS5B inhibitors, another class of DAAs 6. Subtitutions at amino acid positions 155, 156, or 168 are known to confer resistance. The substitutions of the enzyme's catalytic triad consisting of H58, D82, and S139 are also likely to alter the affinity of the drug for NS3/4A or the activity of the enzyme itself. Despite this disadvantage Telaprevir is still effective against HCV when paired with Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b.
Telaprevir, Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b were used with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily administration of the combination therapy followed by 12 or 36 weeks of therapy with Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b. 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 5.
Telaprevir was available as a fixed dose product (tradename Incivek) used for the treatment of chronic Hepatitis C. Approved in May 2011 by the FDA, Incivek was indicated for the treatment of HCV genotype 1 in combination with Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b Label. Incivek has since been withdrawn from the market.
- Type
- Small Molecule
- Groups
- Approved, Withdrawn
- Structure
Structure for Telaprevir (DB05521)
- Weight
- Average: 679.8493
Monoisotopic: 679.405732463 - Chemical Formula
- C36H53N7O6
- Synonyms
- (1S,3aR,6aS)-(2S)-2-cyclohexyl-N-(pyrazinylcarbonyl)glycyl-3-methyl-L-valyl-N-((1S)-1-((cyclopropylamino)oxoacetyl)butyl)octahydrocyclopenta(c)pyrrole-1-carboxamide
- Telaprevir
- External IDs
- AIDS-213006
- AIDS213006
- LY 570310
- LY-570310
- MP 424
- MP-424
- VRT 111950
- VRT-111950
- VRT111950
- VX 950
- VX-950
Pharmacology
- Indication
Telaprevir, when used in combination with Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b is indicated for use in the treatment of chronic HCV genotype 1 infection in adults 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 1 Regimen in combination with: Peginterferon alfa-2b (DB00022), Ribavirin (DB00811) •••••••••••• ••••• •••••• Used in combination to treat Chronic hepatitis c genotype 1 Regimen in combination with: Peginterferon alfa-2b (DB00022), 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
Telaprevir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotype 1 Label.
- Mechanism of action
Telaprevir is a NS3/4a protease inhibitor used to inhibit viral HCV replication Label. NS3/4a protease is an integral part of viral replication and mediates the cleavage the virally encoded polyprotein to mature proteins (NS4A, NS4B, NS5A and NS5B) Label. Telaprevir inhibits NS3/4A with an IC50 of 10nM.
Target Actions Organism AGenome polyprotein modulatorAGenome polyprotein inhibitorHepatitis C Virus USolute carrier organic anion transporter family member 1B1 inhibitorHumans USolute carrier organic anion transporter family member 2B1 inhibitorHumans - Absorption
Telaprevir reaches peak plasma concentration 4-5hours after administration Label. Absolute bioavailability has not been determined. When taken with a normal fat meal (21g of fat), exposure increases by 235% compared to fasting conditions. With low (3.6g of fat) and high fat (56g of fat) meals, exposure increased 117% and 330% respectively.
- Volume of distribution
The estimated apparent volume of distribution for Telapravir is 252 litres with an inter-individual variability of 72% Label.
- Protein binding
Telapravir is 59-76% bound to human plasma proteins following a single dose Label. It binds to both human serum albumin and α1-acid glycoprotein.
- Metabolism
Telaprevir is extensively metabolized via hydrolysis, oxidation, and reduction. The major metabolites of Telaprevir are pyrazinoic acid, a metabolite that underwent reduction at the α-ketoamide bond, and the R-diastereomer of telaprevir which is 30-fold less active than the parent compound were found to be the predominant metabolites. The primary enzyme involved in the metabolism of Telaprevir is CYP3A4. Some metabolism is performed by aldo-keto reductases and other reductases.
Hover over products below to view reaction partners
- Route of elimination
Telaprevir is mainly eliminated in the feces (82%) with a smaller amount eliminated via expiration (9%) and very little in the urine (1%) Label. 31.9% and 18.8% of drug in the feces was present as the parent compound and R-diastereomer of the parent compound respectively.
- Half-life
Telaprevir has a half-life of elimination of 4.0-4.7 hours after a single dose and an effective half life of 9-11 hours at steady state Label.
- Clearance
Telaprevir has an estimated aparent total body clearance of 32.4 liters per hour with an interindividual variability of 27.2% Label.
- 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
Serious skin reactions, including Stevens Johnson Syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms, and Toxic Epidermal Necrolysis, have been reported in patients treated with telaprevir combination treatment. Use of Ribavirin, Peginterferon alfa-2a, Peginterferon alfa-2b and Telaprevir is associated with a further increase in anemia frequency than in Ribavirin, Peginterferon alfa-2a, and Peginterferon alfa-2b without telaprevir.
- 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 software1,2-Benzodiazepine The metabolism of 1,2-Benzodiazepine can be decreased when combined with Telaprevir. Abametapir The serum concentration of Telaprevir can be increased when it is combined with Abametapir. Abatacept The metabolism of Telaprevir can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Telaprevir. Abiraterone The metabolism of Abiraterone can be decreased when combined with Telaprevir. - Food Interactions
- Avoid St. John's Wort. St. John's Wort will decrease levels of this medication.
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.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Incivek Tablet 375 mg Oral Vertex Pharmaceuticals Incorporated 2011-10-03 2015-04-21 Canada 
Incivek Tablet, film coated 375 mg/1 Oral Vertex Pharmaceuticals Incorporated 2011-05-23 2014-10-16 US 
Incivo Tablet, film coated 375 mg Oral Janssen Cilag International Nv 2016-09-08 2016-06-29 EU 
Incivo Tablet, film coated 375 mg Oral Janssen Cilag International Nv 2016-09-08 2016-06-29 EU
Categories
- ATC Codes
- J05AP02 — Telaprevir
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Antivirals for treatment of HCV infections
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strong)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Direct Acting Antivirals
- Enzyme Inhibitors
- HCV NS3/4A Protease Inhibitors
- NS3/4A Protease Inhibitors
- OATP1B1/SLCO1B1 Inhibitors
- Organic Anion Transporting Polypeptide 1B1 Inhibitors
- Organic Anion Transporting Polypeptide 2B1 Inhibitors
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Peptides
- Protease Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as hybrid peptides. These are compounds containing at least two different types of amino acids (alpha, beta, gamma, delta) linked to each other through a peptide bond.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Peptidomimetics
- Sub Class
- Hybrid peptides
- Direct Parent
- Hybrid peptides
- Alternative Parents
- Valine and derivatives / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Pyrazinecarboxamides / 2-heteroaryl carboxamides / N-acylpyrrolidines / Pyrrolidinecarboxamides / N-acyl amines / Tertiary carboxylic acid amides / Heteroaromatic compounds show 7 more
- Substituents
- 2-heteroaryl carboxamide / Alpha-amino acid amide / Alpha-amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Fatty acyl / Fatty amide show 24 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- oligopeptide, pyrazines, cyclopropanes, cyclopentapyrrole (CHEBI:68595)
- Affected organisms
- Hepatitis C Virus
Chemical Identifiers
- UNII
- 655M5O3W0U
- CAS number
- 402957-28-2
- InChI Key
- BBAWEDCPNXPBQM-GDEBMMAJSA-N
- InChI
- InChI=1S/C36H53N7O6/c1-5-10-25(29(44)34(48)39-23-15-16-23)40-33(47)28-24-14-9-13-22(24)20-43(28)35(49)30(36(2,3)4)42-32(46)27(21-11-7-6-8-12-21)41-31(45)26-19-37-17-18-38-26/h17-19,21-25,27-28,30H,5-16,20H2,1-4H3,(H,39,48)(H,40,47)(H,41,45)(H,42,46)/t22-,24-,25-,27-,28-,30+/m0/s1
- IUPAC Name
- (3S)-3-{[(1S,3aR,6aS)-2-[(2S)-2-[(2S)-2-cyclohexyl-2-[(pyrazin-2-yl)formamido]acetamido]-3,3-dimethylbutanoyl]-octahydrocyclopenta[c]pyrrol-1-yl]formamido}-N-cyclopropyl-2-oxohexanamide
- SMILES
- [H][C@@]12CCC[C@]1([H])[C@H](N(C2)C(=O)[C@@H](NC(=O)[C@@H](NC(=O)C1=NC=CN=C1)C1CCCCC1)C(C)(C)C)C(=O)N[C@@H](CCC)C(=O)C(=O)NC1CC1
References
- Synthesis Reference
Znabet A, Polak MM, Janssen E, de Kanter FJ, Turner NJ, Orru RV, Ruijter E. A highly efficient synthesis of telaprevir by strategic use of biocatalysis and multicomponent reactions. Chem Commun (Camb). 2010 Nov 14;46(42):7918-20. Epub 2010 Sep 20.
- General References
- Kim JJ, Culley CM, Mohammad RA: Telaprevir: an oral protease inhibitor for hepatitis C virus infection. Am J Health Syst Pharm. 2012 Jan 1;69(1):19-33. doi: 10.2146/ajhp110123. [Article]
- Liu-Young G, Kozal MJ: Hepatitis C protease and polymerase inhibitors in development. AIDS Patient Care STDS. 2008 Jun;22(6):449-57. doi: 10.1089/apc.2007.0199. [Article]
- Forestier N, Zeuzem S: Telaprevir for the treatment of hepatitis C. Expert Opin Pharmacother. 2012 Mar;13(4):593-606. doi: 10.1517/14656566.2012.660524. Epub 2012 Feb 15. [Article]
- Garg V, Kauffman RS, Beaumont M, van Heeswijk RP: Telaprevir: pharmacokinetics and drug interactions. Antivir Ther. 2012;17(7):1211-21. doi: 10.3851/IMP2356. Epub 2012 Sep 7. [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]
- 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]
- American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
- FDA Approved Drug Products: Incivek (telaprevir) oral tablets [Link]
- External Links
- Human Metabolome Database
- HMDB0015616
- KEGG Drug
- D09012
- PubChem Compound
- 3010818
- PubChem Substance
- 175427024
- ChemSpider
- 2279948
- BindingDB
- 50326056
- 1102261
- ChEBI
- 68595
- ChEMBL
- CHEMBL231813
- ZINC
- ZINC000003992480
- PharmGKB
- PA165958354
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Telaprevir
- FDA label
- Download (508 KB)
- MSDS
- Download (88.2 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 data4 Completed Treatment Chronic Hepatitis C Virus (HCV) Infection 1 somestatus stop reason just information to hide 4 Completed Treatment Hepatitis C Virus (HCV) Infection 1 somestatus stop reason just information to hide 4 Terminated Treatment Hepatitis C Virus (HCV) Infection 2 somestatus stop reason just information to hide 4 Withdrawn Prevention Hepatitis C Virus (HCV) Infection 1 somestatus stop reason just information to hide 4 Withdrawn Treatment Hepatitis C Virus (HCV) Infection 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 375 mg Tablet, film coated Oral 375 mg/1 Tablet, film coated Oral Tablet, film coated Oral 375 mg Tablet, coated Oral 375 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8431615 No 2013-04-30 2028-05-30 US US8529882 No 2013-09-10 2021-08-31 US US7820671 No 2010-10-26 2025-02-25 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility 0.0047 mg/mL FDA Label - Predicted Properties
Property Value Source Water Solubility 0.0355 mg/mL ALOGPS logP 2.56 ALOGPS logP 2.58 Chemaxon logS -4.3 ALOGPS pKa (Strongest Acidic) 11.86 Chemaxon pKa (Strongest Basic) -0.58 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 179.56 Å2 Chemaxon Rotatable Bond Count 14 Chemaxon Refractivity 180.04 m3·mol-1 Chemaxon Polarizability 73.79 Å3 Chemaxon Number of Rings 5 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
Property Value Probability Human Intestinal Absorption + 0.9547 Blood Brain Barrier - 0.9659 Caco-2 permeable - 0.7982 P-glycoprotein substrate Substrate 0.8567 P-glycoprotein inhibitor I Inhibitor 0.9355 P-glycoprotein inhibitor II Inhibitor 0.8879 Renal organic cation transporter Non-inhibitor 0.8919 CYP450 2C9 substrate Non-substrate 0.8245 CYP450 2D6 substrate Non-substrate 0.6612 CYP450 3A4 substrate Substrate 0.7632 CYP450 1A2 substrate Non-inhibitor 0.6961 CYP450 2C9 inhibitor Inhibitor 0.5969 CYP450 2D6 inhibitor Non-inhibitor 0.7431 CYP450 2C19 inhibitor Inhibitor 0.5866 CYP450 3A4 inhibitor Inhibitor 0.8926 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8476 Ames test Non AMES toxic 0.7536 Carcinogenicity Non-carcinogens 0.8622 Biodegradation Not ready biodegradable 0.9954 Rat acute toxicity 2.6980 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9894 hERG inhibition (predictor II) Inhibitor 0.6931
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 263.3125041 predictedDarkChem Lite v0.1.0 [M-H]- 255.8990041 predictedDarkChem Lite v0.1.0 [M-H]- 247.4829 predictedDeepCCS 1.0 (2019) [M+H]+ 261.7451041 predictedDarkChem Lite v0.1.0 [M+H]+ 255.6741041 predictedDarkChem Lite v0.1.0 [M+H]+ 249.69911 predictedDeepCCS 1.0 (2019) [M+Na]+ 263.2733041 predictedDarkChem Lite v0.1.0 [M+Na]+ 254.9812041 predictedDarkChem Lite v0.1.0 [M+Na]+ 255.84802 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Not Available
- Pharmacological action
- Yes
- Actions
- Modulator
- 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
- Hepatitis C Virus
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type peptidase activity
- Specific Function
- Not Available
- Gene Name
- NS3/4A
- Uniprot ID
- B0B3C9
- Uniprot Name
- Genome polyprotein
- Molecular Weight
- 72789.28 Da
References
- Liu-Young G, Kozal MJ: Hepatitis C protease and polymerase inhibitors in development. AIDS Patient Care STDS. 2008 Jun;22(6):449-57. doi: 10.1089/apc.2007.0199. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
- Specific Function
- Bile acid transmembrane transporter activity
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent transport of steroid sulfate conjugates and other specific organic anions (PubMed:10873595, PubMed:11159893, PubMed:11932330, PubMed:12724351, PubMed:14610227, PubMed:16908597, PubMed:18501590, PubMed:20507927, PubMed:22201122, PubMed:23531488, PubMed:25132355, PubMed:26383540, PubMed:27576593, PubMed:28408210, PubMed:29871943, PubMed:34628357). Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) (PubMed:11932330, PubMed:12409283). Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver (PubMed:11159893). Mediates the intestinal uptake of sulfated steroids (PubMed:12724351, PubMed:28408210). Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain (PubMed:16908597, PubMed:25132355). Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC (PubMed:35714613). Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition (PubMed:26383540). Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, PubMed:29871943, Ref.25). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:14610227, PubMed:19129463, PubMed:22201122). The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound (PubMed:19129463, PubMed:20507927, PubMed:26277985). Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions (PubMed:19129463). Cytoplasmic glutamate may also act as counteranion in the placenta (PubMed:26277985). An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) (PubMed:20507927)
- Specific Function
- Bile acid transmembrane transporter activity
- Gene Name
- SLCO2B1
- Uniprot ID
- O94956
- Uniprot Name
- Solute carrier organic anion transporter family member 2B1
- Molecular Weight
- 76697.93 Da
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- Kim JJ, Culley CM, Mohammad RA: Telaprevir: an oral protease inhibitor for hepatitis C virus infection. Am J Health Syst Pharm. 2012 Jan 1;69(1):19-33. doi: 10.2146/ajhp110123. [Article]
- Kiang TK, Wilby KJ, Ensom MH: Telaprevir: clinical pharmacokinetics, pharmacodynamics, and drug-drug interactions. Clin Pharmacokinet. 2013 Jul;52(7):487-510. doi: 10.1007/s40262-013-0053-x. [Article]
- Rangnekar AS, Fontana RJ: Managing drug-drug interactions with boceprevir and telaprevir. Clin Liver Dis (Hoboken). 2012 Apr 26;1(2):36-40. doi: 10.1002/cld.10. eCollection 2012 Apr. [Article]
- Flockhart Table of Drug Interactions [Link]
- Telaprevir FDA label [File]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- 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
- Garg V, Kauffman RS, Beaumont M, van Heeswijk RP: Telaprevir: pharmacokinetics and drug interactions. Antivir Ther. 2012;17(7):1211-21. doi: 10.3851/IMP2356. Epub 2012 Sep 7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- 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
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23539.43 Da
References
- Garg V, Kauffman RS, Beaumont M, van Heeswijk RP: Telaprevir: pharmacokinetics and drug interactions. Antivir Ther. 2012;17(7):1211-21. doi: 10.3851/IMP2356. Epub 2012 Sep 7. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
Drug created at November 18, 2007 18:25 / Updated at August 26, 2024 19:24