Tezacaftor
Identification
- Summary
Tezacaftor is a medication used to treat homozygous or heterozygous F508del mutation cystic fibrosis.
- Brand Names
- Symdeko, Trikafta (100 Mg / 50 Mg / 75 Mg; 150 Mg)
- Generic Name
- Tezacaftor
- DrugBank Accession Number
- DB11712
- Background
Tezacaftor is a drug of the cystic fibrosis transmembrane conductance regulator (CFTR) potentiator class.10 It was developed by Vertex Pharmaceuticals and FDA approved in combination with ivacaftor to manage cystic fibrosis.14 This drug was approved by the FDA on February 12, 2018.15
Cystic Fibrosis is an autosomal recessive disorder caused by one of several different mutations in the gene for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, an ion channel involved in the transport of chloride and sodium ions across cell membranes. CFTR is active in epithelial cells of organs such as of the lungs, pancreas, liver, digestive system, and reproductive tract. Alterations in the CFTR gene result in altered production, misfolding, or function of the protein and consequently abnormal fluid and ion transport across cell membranes.5,6 As a result, CF patients produce thick, sticky mucus that clogs the ducts of organs where it is produced making patients more susceptible to complications such as infections, lung damage, pancreatic insufficiency, and malnutrition.7
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 520.505
Monoisotopic: 520.182121086 - Chemical Formula
- C26H27F3N2O6
- Synonyms
- Tezacaftor
- External IDs
- VX 661
- VX-661
- VX661
Pharmacology
- Indication
Tezacaftor is combined with ivacaftor in one product for the treatment of cystic fibrosis (CF) in patients aged 12 years or older with two copies of the F508del gene mutation or at least one mutation in the CFTR gene that is responsive to this drug.14
Tezacaftor, when used in combination with ivacaftor and elexacaftor in the product Trikafta, is also indicated for the treatment of CF in patients 12 years of age and older that have at least one F508del mutation in the CFTR gene.19
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 manage Cystic fibrosis Combination Product in combination with: Ivacaftor (DB08820), Elexacaftor (DB15444) •••••••••••• ••••••• Used in combination to manage Cystic fibrosis Combination Product in combination with: Elexacaftor (DB15444), Ivacaftor (DB08820) •••••••••••• •••••• Used in combination to treat Cystic fibrosis Combination Product in combination with: Ivacaftor (DB08820) •••••••••••• •• ••••• ••• •••••••• •• ••• •••••• •••••••• ••••••••••••• ••••••••••• ••••••••• •••••• •••• •••• •• •••••••••• •• •••••••••••••••••••• Used in combination to treat Cystic fibrosis Combination Product in combination with: Ivacaftor (DB08820) •••••••••••• •••••• ••••••••• •••••••••• ••• ••• ••••••• •••• •••••••• - 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
Clinical studies have shown a significant decrease in sweat chloride and an increase in the forced expiratory volume (FEV), a measure of lung function, following Tevacaftor/Ivacaftor therapy.1 Phase 3 clinical studies have shown that a significant increase in forced expiratory volume was attained at 4 and 8 weeks after initiating this drug. The above effects lead to improvement of the respiratory symptoms of cystic fibrosis. Tezacaftor does not induce clinically significant QT prolongation.2 When given with ivacaftor, tezacaftor can lead to liver transaminase elevations.14 Testing of transaminases (ALT and AST) levels should occur before starting this combination every 3 months during the first year of treatment, and every year afterwards. Patients with a history of transaminase elevations should be monitored more frequently.14
- Mechanism of action
The transport of charged ions across cell membranes is normally achieved through the actions of the cystic fibrosis transmembrane regulator (CFTR) protein. This protein acts as a channel and allows for the passage of chloride and sodium. This process affects the movement of water in and out of the tissues and impacts the production of mucus that lubricates and protects certain organs and body tissues, including the lungs. In the F508del mutation of the CFTR gene, one amino acid is deleted at the position 508, therefore, the CFTR channel function is compromised, resulting in thickened mucus secretions.10 CFTR correctors such as tezacaftor aim to repair F508del cellular misprocessing.9 This is done by modulating the position of the CFTR protein on the cell surface to the correct position, allowing for adequate ion channel formation and increased in water and salt movement through the cell membrane.10 The concomitant use of ivacaftor is intended to maintain an open channel, increasing the transport of chloride, reducing thick mucus production.13
Target Actions Organism ACystic fibrosis transmembrane conductance regulator positive allosteric modulatorHumans - Absorption
The Cmax, Tmax and AUC of tezacaftor, when administered with ivacaftor, are 5.95 mcg/ml, 2-6 h, and 84.5 mcg.h/ml respectively.14 Exposure of tezacaftor/ivacaftor increases 3-fold when it is administered with a high-fat meal.14
- Volume of distribution
The apparent volume of distribution of tezacaftor was 271 L in a study of patients in the fed state who received 100 mg of tezacaftor every 12 hours.14
- Protein binding
Tezacaftor is approximately 99% bound to plasma proteins, mainly albumin.14
- Metabolism
Tezacaftor is metabolized extensively in humans by the action of CYP3A4 and CYP3A5. There are three main circulating metabolites; M1, M2, and M5. The M1 is an active metabolite with similar activity to the parent drug, tezacaftor. The M2 metabolite is significantly less active and M5 is considered an inactive metabolite.4,14 An additional circulating metabolite, M3, corresponding to the glucuronide form of tezacaftor.14
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- Route of elimination
After oral administration, the majority of tezacaftor dose (72%) is found excreted in the feces either unchanged or as its metabolite, M2. About 14% of the administered dose is found excreted in the urine as the metabolite, M2. It was noted that less than 1% of the administered dose is excreted unchanged in the urine and thus, renal excretion is not the major elimination pathway.14
- Half-life
The apparent half-life of tezacaftor is approximately 57.2 hours.4,18
- Clearance
The apparent clearance of tezacaftor has been measured at 1.31 L/h for patients in the fed state during a clinical trial.3
- 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 LD50 of an oral dose in rats is >2000 mg/kg.17
Overdose symptoms may include dizziness and diarrhea. There have been no reports to this date of tezacaftor overdose, but the highest dose of 450 mg every 12 hours commonly resulted in reports of dizziness and diarrhea. No antidote exists for treating an overdose with this drug. General supportive measures should be undertaken along with monitoring of vital signs and close monitoring of clinical status.14
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 softwareAbametapir The serum concentration of Tezacaftor can be increased when it is combined with Abametapir. Abatacept The metabolism of Tezacaftor can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Tezacaftor. Abrocitinib The serum concentration of Tezacaftor can be increased when it is combined with Abrocitinib. Acalabrutinib The metabolism of Tezacaftor can be decreased when combined with Acalabrutinib. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of tezacaftor.
- Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of tezacaftor.
- Take with food. Tezacaftor should be taken with fat-containing food to increase exposure.
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.
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Kaftrio Tezacaftor (25 mg) + Elexacaftor (50 mg) + Ivacaftor (37.5 mg) Tablet, film coated Oral Vertex Pharmaceuticals (Ireland) Limited 2022-05-04 Not applicable EU Kaftrio Tezacaftor (50 mg) + Elexacaftor (100 mg) + Ivacaftor (75 mg) Tablet, film coated Oral Vertex Pharmaceuticals (Ireland) Limited 2020-12-15 Not applicable EU KAFTRIO Tezacaftor (50 MG) + Elexacaftor (100 MG) + Ivacaftor (75 MG) Tablet, film coated Oral Vertex Pharmaceuticals (Ireland) Limited 2020-11-14 Not applicable Italy Symdeko Tezacaftor (50 mg/1) + Ivacaftor (75 mg/1) + Ivacaftor (75 mg/1) Kit; Tablet, film coated Oral Vertex Pharmaceuticals Incorporated 2019-06-21 Not applicable US Symdeko Tezacaftor (100 mg) + Ivacaftor (150 mg) + Ivacaftor (150 mg) Tablet Oral Vertex Pharmaceuticals Incorporated 2018-06-28 Not applicable Canada
Categories
- ATC Codes
- R07AX32 — Ivacaftor, tezacaftor and elexacaftor
- R07AX — Other respiratory system products
- R07A — OTHER RESPIRATORY SYSTEM PRODUCTS
- R07 — OTHER RESPIRATORY SYSTEM PRODUCTS
- R — RESPIRATORY SYSTEM
- Drug Categories
- BCRP/ABCG2 Inhibitors
- BCRP/ABCG2 Substrates
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Inducers
- Cytochrome P-450 CYP3A5 Inducers (strength unknown)
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Dioxoles
- Heterocyclic Compounds, Fused-Ring
- OAT1/SLC22A6 inhibitors
- OAT3/SLC22A8 Inhibitors
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B1/SLCO1B1 Substrates
- OATP1B3 inhibitors
- OCT2 Inhibitors
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as n-alkylindoles. These are compounds containing an indole moiety that carries an alkyl chain at the 1-position.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- N-alkylindoles
- Direct Parent
- N-alkylindoles
- Alternative Parents
- Indoles / Benzodioxoles / N-arylamides / Substituted pyrroles / Aryl fluorides / Benzenoids / Cyclopropanecarboxylic acids and derivatives / Heteroaromatic compounds / Secondary carboxylic acid amides / Secondary alcohols show 9 more
- Substituents
- 1,2-diol / Alcohol / Alkyl fluoride / Alkyl halide / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Benzodioxole show 22 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 8RW88Y506K
- CAS number
- 1152311-62-0
- InChI Key
- MJUVRTYWUMPBTR-MRXNPFEDSA-N
- InChI
- InChI=1S/C26H27F3N2O6/c1-24(2,13-33)22-8-14-7-18(17(27)10-19(14)31(22)11-16(34)12-32)30-23(35)25(5-6-25)15-3-4-20-21(9-15)37-26(28,29)36-20/h3-4,7-10,16,32-34H,5-6,11-13H2,1-2H3,(H,30,35)/t16-/m1/s1
- IUPAC Name
- 1-(2,2-difluoro-2H-1,3-benzodioxol-5-yl)-N-{1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl}cyclopropane-1-carboxamide
- SMILES
- CC(C)(CO)C1=CC2=CC(NC(=O)C3(CC3)C3=CC=C4OC(F)(F)OC4=C3)=C(F)C=C2N1C[C@@H](O)CO
References
- General References
- Donaldson SH, Pilewski JM, Griese M, Cooke J, Viswanathan L, Tullis E, Davies JC, Lekstrom-Himes JA, Wang LT: Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR. Am J Respir Crit Care Med. 2018 Jan 15;197(2):214-224. doi: 10.1164/rccm.201704-0717OC. [Article]
- Taylor-Cousar JL, Munck A, McKone EF, van der Ent CK, Moeller A, Simard C, Wang LT, Ingenito EP, McKee C, Lu Y, Lekstrom-Himes J, Elborn JS: Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del. N Engl J Med. 2017 Nov 23;377(21):2013-2023. doi: 10.1056/NEJMoa1709846. Epub 2017 Nov 3. [Article]
- Rowe SM, Daines C, Ringshausen FC, Kerem E, Wilson J, Tullis E, Nair N, Simard C, Han L, Ingenito EP, McKee C, Lekstrom-Himes J, Davies JC: Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis. N Engl J Med. 2017 Nov 23;377(21):2024-2035. doi: 10.1056/NEJMoa1709847. Epub 2017 Nov 3. [Article]
- Garg V, Shen J, Li C, Agarwal S, Gebre A, Robertson S, Huang J, Han L, Jiang L, Stephan K, Wang LT, Lekstrom-Himes J: Pharmacokinetic and Drug-Drug Interaction Profiles of the Combination of Tezacaftor/Ivacaftor. Clin Transl Sci. 2019 May;12(3):267-275. doi: 10.1111/cts.12610. Epub 2019 Jan 29. [Article]
- Saint-Criq V, Gray MA: Role of CFTR in epithelial physiology. Cell Mol Life Sci. 2017 Jan;74(1):93-115. doi: 10.1007/s00018-016-2391-y. Epub 2016 Oct 6. [Article]
- Kunzelmann K, Mall M: Pharmacotherapy of the ion transport defect in cystic fibrosis: role of purinergic receptor agonists and other potential therapeutics. Am J Respir Med. 2003;2(4):299-309. [Article]
- Fraser-Pitt D, O'Neil D: Cystic fibrosis - a multiorgan protein misfolding disease. Future Sci OA. 2015 Sep 1;1(2):FSO57. doi: 10.4155/fso.15.57. eCollection 2015 Sep. [Article]
- Fohner AE, McDonagh EM, Clancy JP, Whirl Carrillo M, Altman RB, Klein TE: PharmGKB summary: ivacaftor pathway, pharmacokinetics/pharmacodynamics. Pharmacogenet Genomics. 2017 Jan;27(1):39-42. doi: 10.1097/FPC.0000000000000246. [Article]
- Rowe SM, Verkman AS: Cystic fibrosis transmembrane regulator correctors and potentiators. Cold Spring Harb Perspect Med. 2013 Jul 1;3(7). pii: 3/7/a009761. doi: 10.1101/cshperspect.a009761. [Article]
- Cystic fibrosis news [Link]
- Vertex news [Link]
- Vertex news [Link]
- Vertex news [Link]
- FDA Approved Drug Products: SYMDEKO (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use (December 2020) [Link]
- FDA Approved Drug Products: Apadaz (benzhydrocodone and acetaminophen) tablets [Link]
- NIH Medline Tezacaftor/Ivacaftor [Link]
- Pharmacology review, FDA [Link]
- Monograph, Tezacaftor/Ivacaftor [Link]
- FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
- FDA Approved Drug Products: TRIKAFTA® (elexacaftor, tezacaftor, and ivacaftor tablets; ivacaftor tablets), co-packaged for oral use May 2023 [Link]
- FDA Approved Drug Products: SYMDEKO™ (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use [Link]
- External Links
- Human Metabolome Database
- HMDB0304895
- KEGG Drug
- D11041
- PubChem Compound
- 46199646
- PubChem Substance
- 347828077
- ChemSpider
- 28637762
- BindingDB
- 281054
- 1999382
- ChEMBL
- CHEMBL3544914
- ZINC
- ZINC000068206930
- PDBe Ligand
- CV6
- Wikipedia
- Tezacaftor
- PDB Entries
- 7sv7 / 8eiq
- FDA label
- Download (459 KB)
- MSDS
- Download (27.1 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Other Adherence, Medication / Cystic Fibrosis (CF) / Cystic Fibrosis Gastrointestinal Disease / Cystic Fibrosis in Children / Cystic Fibrosis Liver Disease 1 4 Recruiting Other Drug Drug Interaction (DDI) 1 4 Recruiting Treatment Cystic Fibrosis (CF) 1 4 Recruiting Treatment Noncystic Fibrosis Bronchiectasis (NCFB) 1 3 Active Not Recruiting Treatment Cystic Fibrosis (CF) 4
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral Tablet, film coated Oral Granule Oral Granule; kit Oral Kit; tablet, film coated Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8324242 No 2012-12-04 2027-04-18 US US8354427 No 2013-01-15 2026-07-06 US US8754224 No 2014-06-17 2026-12-28 US US8410274 No 2013-04-02 2026-12-28 US US7495103 No 2009-02-24 2027-05-20 US US8883206 No 2014-11-11 2033-02-27 US US9670163 No 2017-06-06 2026-12-28 US US8415387 No 2013-04-09 2027-11-12 US US9012496 No 2015-04-21 2033-07-15 US US8598181 No 2013-12-03 2027-05-01 US US8629162 No 2014-01-14 2025-06-24 US US8623905 No 2014-01-07 2027-05-01 US US7645789 No 2010-01-12 2027-05-01 US US7776905 No 2010-08-17 2027-06-03 US US9931334 No 2018-04-03 2026-12-28 US US9974781 No 2018-05-22 2027-04-09 US US10022352 No 2018-07-17 2027-04-09 US US10058546 No 2018-08-28 2033-07-15 US US10081621 No 2018-09-25 2031-03-25 US US10206877 No 2019-02-19 2035-04-14 US US10239867 No 2019-03-26 2027-04-09 US US10272046 No 2019-04-30 2033-02-27 US US10646481 No 2020-05-12 2029-08-13 US US10758534 No 2020-09-01 2035-10-06 US US10793547 No 2020-10-06 2037-12-08 US US11179367 No 2021-11-23 2037-12-08 US US11147770 No 2021-10-19 2033-02-27 US US11426407 No 2015-10-06 2035-10-06 US US11453655 No 2017-12-08 2037-12-08 US US11517564 No 2017-12-08 2037-12-08 US US11564916 No 2009-08-13 2029-08-13 US US11578062 No 2011-03-25 2031-03-25 US US11639347 No 2007-04-09 2027-04-09 US US11752106 No 2013-02-27 2033-02-27 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Insoluble in water https://www.medkoo.com/products/4790 logP 99 https://www.medkoo.com/uploads/product/Tezacaftor__VX-661_/safety/MSDS-VX661.pdf pKa 13.99, 0.19 https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL3544914/ - Predicted Properties
Property Value Source Water Solubility 0.0124 mg/mL ALOGPS logP 2.97 ALOGPS logP 4.03 Chemaxon logS -4.6 ALOGPS pKa (Strongest Acidic) 11.54 Chemaxon pKa (Strongest Basic) -2.8 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 113.18 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 125.53 m3·mol-1 Chemaxon Polarizability 51.79 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 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]- 221.48015 predictedDeepCCS 1.0 (2019) [M+H]+ 223.87572 predictedDeepCCS 1.0 (2019) [M+Na]+ 229.78825 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Positive allosteric modulator
- General Function
- Pdz domain binding
- Specific Function
- Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter. Can inhibit the chloride channel activity of ANO...
- Gene Name
- CFTR
- Uniprot ID
- P13569
- Uniprot Name
- Cystic fibrosis transmembrane conductance regulator
- Molecular Weight
- 168139.895 Da
References
- Donaldson SH, Pilewski JM, Griese M, Cooke J, Viswanathan L, Tullis E, Davies JC, Lekstrom-Himes JA, Wang LT: Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR. Am J Respir Crit Care Med. 2018 Jan 15;197(2):214-224. doi: 10.1164/rccm.201704-0717OC. [Article]
- Taylor-Cousar JL, Munck A, McKone EF, van der Ent CK, Moeller A, Simard C, Wang LT, Ingenito EP, McKee C, Lu Y, Lekstrom-Himes J, Elborn JS: Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del. N Engl J Med. 2017 Nov 23;377(21):2013-2023. doi: 10.1056/NEJMoa1709846. Epub 2017 Nov 3. [Article]
- Saint-Criq V, Gray MA: Role of CFTR in epithelial physiology. Cell Mol Life Sci. 2017 Jan;74(1):93-115. doi: 10.1007/s00018-016-2391-y. Epub 2016 Oct 6. [Article]
- Cystic fibrosis news [Link]
- FDA Approved Drug Products: SYMDEKO (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use (December 2020) [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitorInducer
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Garg V, Shen J, Li C, Agarwal S, Gebre A, Robertson S, Huang J, Han L, Jiang L, Stephan K, Wang LT, Lekstrom-Himes J: Pharmacokinetic and Drug-Drug Interaction Profiles of the Combination of Tezacaftor/Ivacaftor. Clin Transl Sci. 2019 May;12(3):267-275. doi: 10.1111/cts.12610. Epub 2019 Jan 29. [Article]
- FDA Approved Drug Products: SYMDEKO (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use (December 2020) [Link]
- Monograph, Tezacaftor/Ivacaftor [Link]
- FDA Approved Drug Products: SYMDEKO™ (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInducer
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Garg V, Shen J, Li C, Agarwal S, Gebre A, Robertson S, Huang J, Han L, Jiang L, Stephan K, Wang LT, Lekstrom-Himes J: Pharmacokinetic and Drug-Drug Interaction Profiles of the Combination of Tezacaftor/Ivacaftor. Clin Transl Sci. 2019 May;12(3):267-275. doi: 10.1111/cts.12610. Epub 2019 Jan 29. [Article]
- FDA Approved Drug Products: SYMDEKO (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use (December 2020) [Link]
- Monograph, Tezacaftor/Ivacaftor [Link]
- FDA Approved Drug Products: SYMDEKO™ (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- FDA Approved Drug Products: Trikafta (elexacaftor, tezacaftor and ivacaftor tablets; ivacaftor tablets) [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Garg V, Shen J, Li C, Agarwal S, Gebre A, Robertson S, Huang J, Han L, Jiang L, Stephan K, Wang LT, Lekstrom-Himes J: Pharmacokinetic and Drug-Drug Interaction Profiles of the Combination of Tezacaftor/Ivacaftor. Clin Transl Sci. 2019 May;12(3):267-275. doi: 10.1111/cts.12610. Epub 2019 Jan 29. [Article]
- FDA Approved Drug Products: SYMDEKO (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use (December 2020) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Quaternary ammonium group transmembrane transporter activity
- Specific Function
- Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Solute carrier family 22 member 8
- Molecular Weight
- 59855.585 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
References
- FDA Approved Drug Products: SYMDEKO™ (tezacaftor/ivacaftor) tablets; (ivacaftor) tablets, for oral use [Link]
Drug created at October 20, 2016 20:41 / Updated at May 15, 2023 23:19