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Identification
- Summary
Voxelotor is a drug used to inhibit the polymerization of hemoglobin S, preventing the painful and sometimes lethal vaso-occlusive crises associated with sickle cell disease.
- Brand Names
- Oxbryta
- Generic Name
- Voxelotor
- DrugBank Accession Number
- DB14975
- Background
Voxelotor is a novel hemoglobin S polymerization inhibitor for the treatment of sickle cell disease. This is a genetically inherited condition most prevalent in the Middle East, Africa, and certain parts of India. Sickle cell disease can lead to excruciating pain, stroke, infection, and various other complications arising from the blockage of blood vessels.8
Voxelotor was granted accelerated FDA approval on November 25 2019, as it is likely to be a promising treatment for the 100,000 individuals in the U.S. suffering from the disease, in addition to 20 million others worldwide.11 It was developed by Global Blood Therapeutics, Inc.11 and is unique from other drugs used to treat sickle cell anemia, such as hydroxyurea, L-glutamine, and crizanlizumab6,5 due to its novel mechanism of action. The EMA approved the use of voxelotor for the treatment of hemolytic anemia associated with sickle cell disease in February 2022.13,14
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Voxelotor (DB14975)
- Weight
- Average: 337.379
Monoisotopic: 337.142641484 - Chemical Formula
- C19H19N3O3
- Synonyms
- Voxelotor
- Voxélotor
- Voxelotorum
- External IDs
- GBT-440
- GBT440
- GTX-011
Pharmacology
- Indication
In the US, voxelotor is indicated to treat sickle cell disease in both adult and pediatric patients aged 4 years and older.9 In Europe, it is indicated for the treatment of hemolytic anemia due to sickle cell disease (SCD) in adults and pediatric patients 12 years of age and older as monotherapy or in combination with hydroxyurea.13
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 Hemolytic anemia Regimen in combination with: Hydroxyurea (DB01005) •••••••••••• ••••••••••• ••••• •••••• Treatment of Hemolytic anemia •••••••••••• ••••••••••• ••••• •••••• Treatment of Sickle cell disease •••••••••••• ••••••••••• •••••• - 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
Voxelotor increases hemoglobin (Hb) oxygen affinity in a dose-dependent manner.9 It has led to up to a 40% increase in hemoglobin in clinical trials.1,2 Voxelotor may inhibit red blood cell sickling, attenuate red blood cell deformability, and reduce whole blood viscosity.7
- Mechanism of action
Sickle cell disease is characterized by deoxygenated sickle hemoglobin (HbS) polymerization. The genetic mutation causing this disease leads to the formation of abnormal, sickle-shaped red blood cells that aggregate and block blood vessels throughout the body, causing vaso-occlusive crises.8 Sickle-shaped red blood cells cannot effectively bind oxygen, thus incapable of allowing normal blood flow to organs.1,5
Voxelotor increases Hb oxygen affinity.2,7,9,13 It binds reversibly to hemoglobin (Hb) by forming a covalent bond with the N‐terminal valine of the α‐chain of the protein, resulting in an allosteric modification of Hb.2 Voxelotor stabilizes the oxygenated Hb state and prevents HbS polymerization by increasing hemoglobin’s affinity for oxygen.7
Target Actions Organism AHemoglobin subunit alpha binderHumans - Absorption
Voxelotor is rapidly absorbed after oral administration, with a plasma Tmax of 2 hours.2,12 Tmax in the red blood cells ranges from 17-24 hours.2 The Cmax in whole blood and red blood cells occur 6 and 18 hours after an oral dose, respectively. Consumption of a high-fat meal with voxelotor significantly increased exposure to the drug during clinical trials.9 After a daily dose of either 300, 600, or 900 mg for a period of 15 days, when steady-state concentrations were reached, the average RBC Cmax for the respective doses were measured to be 4950, 9610 and 14 000 μg*h mL−1, respectively.2
- Volume of distribution
The apparent volume of distribution of voxelotor in the central compartment is 338L and 72.2L in the plasma.9
- Protein binding
The protein binding of voxeletor is 99.8% in vitro.9
- Metabolism
Voxeletor is heavily metabolized via two phases. Phase I metabolism consists of oxidation and reduction, while phase II metabolism consists of glucuronidation. Voseletor is oxidized mainly by CYP3A4 and by CYP2C19, CYP2B6, and CYP2C9, to a lesser extent.9,12
- Route of elimination
About 62.6% of the oral dose is found in the feces, of which 33.3% is an unchanged drug. About 35.5% of the dose is recovered in urine, with only 0.08% as the unchanged drug.2,9,12
- Half-life
The plasma elimination half-life of voxelotor in sickle cell disease patients is about 35.5 hours.9 The mean half-life in the red blood cell is 60 days. In one study, the average plasma half-life of voxelotor was 50 hours in patients with sickle cell disease, compared with 61–85 hours in healthy subjects.2
- Clearance
The apparent oral clearance of voxelotor is approximately 6.7 L/h.9
- 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 information and overdose information is unavailable at this time. Current clinical study results suggest that dose-limiting toxicities of voxelotor are unlikely.2
- 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 softwareAbametapir The serum concentration of Voxelotor can be increased when it is combined with Abametapir. Abatacept The metabolism of Voxelotor can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Voxelotor. Abrocitinib The metabolism of Voxelotor can be decreased when combined with Abrocitinib. Acalabrutinib The serum concentration of Acalabrutinib can be increased when it is combined with Voxelotor. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of voxelotor.
- Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of voxelotor.
- Take with or without 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.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Oxbryta Tablet, film coated 500 mg Oral Pfizer Europe Ma Eeig 2022-05-04 Not applicable EU 
Oxbryta Tablet, film coated 500 mg/1 Oral Global Blood Therapeutics, Inc, A subsidiary of Pfizer Inc. 2019-11-25 Not applicable US 
Oxbryta Tablet, film coated 300 mg/1 Oral Global Blood Therapeutics, Inc, A subsidiary of Pfizer Inc. 2019-11-25 Not applicable US Oxbryta Tablet, for suspension 300 mg/1 Oral Global Blood Therapeutics, Inc, A subsidiary of Pfizer Inc. 2021-12-17 Not applicable US
Categories
- ATC Codes
- B06AX03 — Voxelotor
- Drug Categories
- Aldehydes
- Blood and Blood Forming Organs
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Hematologic Agents
- Hemoglobin S Polymerization Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as hydroxybenzaldehydes. These are organic aromatic compounds containing a benzene ring carrying an aldehyde group and a hydroxyl group.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Carbonyl compounds
- Direct Parent
- Hydroxybenzaldehydes
- Alternative Parents
- Phenoxy compounds / Phenol ethers / Benzoyl derivatives / Alkyl aryl ethers / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Pyridines and derivatives / Vinylogous acids / Pyrazoles / Heteroaromatic compounds show 4 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / Alkyl aryl ether / Aromatic heteromonocyclic compound / Azacycle / Azole / Benzenoid / Benzoyl / Ether / Heteroaromatic compound show 13 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 3ZO554A4Q8
- CAS number
- 1446321-46-5
- InChI Key
- FWCVZAQENIZVMY-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H19N3O3/c1-13(2)22-16(8-10-21-22)19-14(5-4-9-20-19)12-25-18-7-3-6-17(24)15(18)11-23/h3-11,13,24H,12H2,1-2H3
- IUPAC Name
- 2-hydroxy-6-({2-[1-(propan-2-yl)-1H-pyrazol-5-yl]pyridin-3-yl}methoxy)benzaldehyde
- SMILES
- CC(C)N1N=CC=C1C1=C(COC2=CC=CC(O)=C2C=O)C=CC=N1
References
- Synthesis Reference
Zhe Li, Nathan Guz, Yiyang Shao, Julieana Cocuz, Markus Frieser, George Petros Yiannikouros, Liang Liao.(2017).US10077249B2.Retrieved from: https://patents.google.com/patent/US10077249B2/en
- General References
- Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A, Hassab H, Achebe MM, Alkindi S, Brown RC, Diuguid DL, Telfer P, Tsitsikas DA, Elghandour A, Gordeuk VR, Kanter J, Abboud MR, Lehrer-Graiwer J, Tonda M, Intondi A, Tong B, Howard J: A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease. N Engl J Med. 2019 Aug 8;381(6):509-519. doi: 10.1056/NEJMoa1903212. Epub 2019 Jun 14. [Article]
- Hutchaleelaha A, Patel M, Washington C, Siu V, Allen E, Oksenberg D, Gretler DD, Mant T, Lehrer-Graiwer J: Pharmacokinetics and pharmacodynamics of voxelotor (GBT440) in healthy adults and patients with sickle cell disease. Br J Clin Pharmacol. 2019 Jun;85(6):1290-1302. doi: 10.1111/bcp.13896. Epub 2019 Mar 31. [Article]
- Howard J, Hemmaway CJ, Telfer P, Layton DM, Porter J, Awogbade M, Mant T, Gretler DD, Dufu K, Hutchaleelaha A, Patel M, Siu V, Dixon S, Landsman N, Tonda M, Lehrer-Graiwer J: A phase 1/2 ascending dose study and open-label extension study of voxelotor in patients with sickle cell disease. Blood. 2019 Apr 25;133(17):1865-1875. doi: 10.1182/blood-2018-08-868893. Epub 2019 Jan 17. [Article]
- Torres L, Conran N: Emerging pharmacotherapeutic approaches for the management of sickle cell disease. Expert Opin Pharmacother. 2019 Feb;20(2):173-186. doi: 10.1080/14656566.2018.1548610. Epub 2018 Nov 30. [Article]
- Ataga KI, Desai PC: Advances in new drug therapies for the management of sickle cell disease. Expert Opin Orphan Drugs. 2018;6(5):329-343. doi: 10.1080/21678707.2018.1471983. Epub 2018 May 14. [Article]
- Yarbro JW: Mechanism of action of hydroxyurea. Semin Oncol. 1992 Jun;19(3 Suppl 9):1-10. [Article]
- Yenamandra A, Marjoncu D: Voxelotor: A Hemoglobin S Polymerization Inhibitor for the Treatment of Sickle Cell Disease. J Adv Pract Oncol. 2020 Nov-Dec;11(8):873-877. doi: 10.6004/jadpro.2020.11.8.7. Epub 2020 Nov 1. [Article]
- Ankit Mangla; Moavia Ehsan; Smita Maruvada (2019). Sickle Cell Anemia. Stat Pearls.
- FDA Approved Drug Products: Oxbryta (voxelotor) tablets, for oral use or oral suspension [Link]
- FDA approves novel treatment to target abnormality in sickle cell disease [Link]
- FDA approves Global Blood Therapeutics sickle cell disease drug [Link]
- Absorption, Metabolism and Excretion of GBT440, a Novel Hemoglobin S (HbS) Polymerization Inhibitor for the Treatment of Sickle Cell Disease (SCD), in Healthy Male Subjects [Link]
- EMA Approved Drug Products: Oxbryta (voxelotor) Oral Tablets [Link]
- GlobeNewswire News Release: European Commission Approves Oxbryta® (voxelotor) for the Treatment of Hemolytic Anemia in Patients with Sickle Cell Disease Age 12 Years and Older [Link]
- External Links
- Human Metabolome Database
- HMDB0304877
- ChemSpider
- 37999268
- BindingDB
- 50235297
- 2265678
- ChEMBL
- CHEMBL4101807
- ZINC
- ZINC000145969085
- Wikipedia
- Voxelotor
- MSDS
- Download (175 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 Available Not Available Sickle Cell Disease (SCD) 1 somestatus stop reason just information to hide Not Available Completed Not Available Sickle Cell Disease (SCD) 1 somestatus stop reason just information to hide Not Available No Longer Available Not Available Sickle Cell Disease (SCD) 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Sickle Cell Disease (SCD) 1 somestatus stop reason just information to hide 4 Completed Treatment Sickle Cell Anemia 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 300 mg/1 Tablet, film coated Oral 500 mg/1 Tablet, film coated Oral 500 mg Tablet, for suspension Oral 300 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US10017491 No 2018-07-10 2032-12-28 US US9447071 No 2016-09-20 2035-02-06 US US10034879 No 2018-07-31 2032-12-28 US US9018210 No 2015-04-28 2032-12-28 US US10493035 No 2019-12-03 2037-10-12 US US9248199 No 2016-02-02 2034-01-29 US US10722502 No 2020-07-28 2035-02-06 US US10806733 No 2020-10-20 2032-12-28 US US11020382 No 2021-06-01 2036-12-02 US US11452720 No 2015-02-06 2035-02-06 US US11944612 No 2016-12-02 2036-12-02 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 80-82 http://drugapprovalsint.com/voxelotor/ boiling point (°C) 539.2±50.0 https://www.chemsrc.com/en/cas/1446321-46-5_1467959.html water solubility insoluble in water https://www.selleckchem.com/products/gbt440.html logP 2.85 https://www.chemsrc.com/en/cas/1446321-46-5_1467959.html pKa 7.67±0.10 https://www.chemicalbook.com/ChemicalProductProperty_EN_CB73053893.htm - Predicted Properties
Property Value Source Water Solubility 0.0526 mg/mL ALOGPS logP 3.02 ALOGPS logP 3.54 Chemaxon logS -3.8 ALOGPS pKa (Strongest Acidic) 8.46 Chemaxon pKa (Strongest Basic) 3.41 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 77.24 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 106.25 m3·mol-1 Chemaxon Polarizability 35.37 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0901000000-66ab3406aafed6ea3f1b Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-0194000000-954b44de092c5544c320 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-02mr-0298000000-655bd56cfdfa3ba9f3cd Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4r-1920000000-651108b26d14dcad8597 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-05bb-0930000000-9f93758125c3534f50ff Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-2941000000-f660a0c78b81e9974d53 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- Curator comments
- Voxelotor binds with the N-terminal valine on the α chain of hemoglobin.
- General Function
- Involved in oxygen transport from the lung to the various peripheral tissues
- Specific Function
- heme binding
- Gene Name
- HBA1
- Uniprot ID
- P69905
- Uniprot Name
- Hemoglobin subunit alpha
- Molecular Weight
- 15257.405 Da
References
- Howard J, Hemmaway CJ, Telfer P, Layton DM, Porter J, Awogbade M, Mant T, Gretler DD, Dufu K, Hutchaleelaha A, Patel M, Siu V, Dixon S, Landsman N, Tonda M, Lehrer-Graiwer J: A phase 1/2 ascending dose study and open-label extension study of voxelotor in patients with sickle cell disease. Blood. 2019 Apr 25;133(17):1865-1875. doi: 10.1182/blood-2018-08-868893. Epub 2019 Jan 17. [Article]
- FDA Approved Drug Products: Oxbryta (voxelotor) tablets, for oral use or oral suspension [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- FDA Approved Drug Products: Oxbryta (voxelotor) tablets, for oral use or oral suspension [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). 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:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- FDA Approved Drug Products: Oxbryta (voxelotor) tablets, for oral use or oral suspension [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). 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 epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- FDA Approved Drug Products: Oxbryta (voxelotor) tablets, for oral use or oral suspension [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). 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:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). 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 imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- FDA Approved Drug Products: Oxbryta (voxelotor) tablets, for oral use or oral suspension [Link]
Drug created at May 20, 2019 14:39 / Updated at January 27, 2023 03:56