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Identification
- Summary
Apixaban is an anticoagulant used for the prophylaxis of stroke and systemic embolism in nonvalvular atrial fibrillation, and deep vein thrombosis(DVT) leading to pulmonary embolism(PE), including in patients after a hip or knee replacement surgery.
- Brand Names
- Eliquis
- Generic Name
- Apixaban
- DrugBank Accession Number
- DB06605
- Background
Apixaban is an oral, direct, and highly selective factor Xa (FXa) inhibitor of both free and bound FXa, as well as prothrombinase, independent of antithrombin III for the prevention and treatment of thromboembolic diseasesLabel,2. It is marketed under the name EliquisLabel,3. Apixaban was approved by the FDA on December 28, 20123.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Apixaban (DB06605)
- Weight
- Average: 459.4971
Monoisotopic: 459.190654313 - Chemical Formula
- C25H25N5O4
- Synonyms
- apixabán
- Apixaban
- apixabanum
- External IDs
- BMS 562247-01
- BMS-562247
- BMS-562247-01
Pharmacology
- Indication
Apixaban is indicated for reducing the risk of stroke and systemic embolism in patients who have nonvalvular atrial fibrillation, prophylaxis of deep vein thrombosis(DVT) leading to pulmonary embolism(PE) in patients after a hip or knee replacement surgery, and treatment of DVT and PE to reduce the risk of recurrenceLabel,1,2.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Prophylaxis of Deep vein thrombosis •••••••••••• •••••• Prophylaxis of Deep vein thrombosis •••••••••••• •••••• Treatment of Deep vein thrombosis •••••••••••• •••••• Treatment of Pulmonary embolism •••••••••••• •••••• Prophylaxis of Recurrent pulmonary embolism •••••••••••• •••••• - Contraindications & Blackbox Warnings
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Apixaban selectively inhibits factor Xa in its free and bound forms, independant of antithrombin IIILabel. Apixaban also inhibits prothrominaseLabel. These effects prevent the formation of a thrombusLabel.
- Mechanism of action
Apixaban selectively inhibits factor Xa in its free and bound forms, independant of antithrombin IIILabel. Apixaban also inhibits prothrominaseLabel. These effects prevent the formation of a thrombusLabel.
Target Actions Organism ACoagulation factor X inhibitorHumans - Absorption
Apixaban is approximately 50% bioavailableLabel though other studies report 43-46% oral bioavailability1.
- Volume of distribution
Approximately 21LLabel.
- Protein binding
92-94%Label.
- Metabolism
50% of the orally administered dose is excreted as the unchanged parent compound, however 25% of the dose is excreted as O-demethyl apixaban sulfateLabel,1. All apixaban metabolites account for approximately 32% of the excreted dose though the structure of all metabolites are not well defined1. Apixaban is mainly metabolized by cytochrome p450(CYP)3A4 and to a lesser extent by CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP2J2Label.
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- Route of elimination
56% of an orally administered dose is recovered in the feces and 24.5-28.8% of the dose is recovered in the urineLabel,1,2. 83-88% of the dose recovered in the urine was the unchanged parent compound1.
- Half-life
- Clearance
- Adverse Effects
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Animal studies have shown an increased risk of maternal bleeding during pregnancy but no increase in fetal malformations or fetal or maternal deathsLabel. It is unknown if this animal data also translates to humans so apixaban should only be used in pregnancy if the benefits outweigh the risksLabel. It is not know whether apixaban is safe and effective in labor and during birth, though animal studies have shown an increased rate of maternal bleedingLabel. Animal studies in rats show apixaban excreted in milk, though it is not know if this also applies to humansLabel. Nursing mothers should either stop breastfeeding or stop taking apixaban depending on the risk and benefit of each optionLabel. Studies to determine safety and effectiveness in pediatric patients have yet to be performedLabel. Studies that involved geriatric patients (at least 75 years old) saw no difference in safety or effectiveness compared to younger patients, though geriatric patients at an especially advanced age may be more susceptible to adverse effectsLabel. Dosage adjustments for patients with end stage renal disease(ESRD) are based on estimates of pharmacokinetic principles and not clinical studyLabel. Patients with ESRD may experience pharmacodynamics similar to those seen in well controlled studies but it may not lead to the same clinical effectsLabel. Dosage adjustments are not necessary in mild hepatic impairmentLabel. In moderate hepatic impairment patients may already experience abnormalities in coagulation and so no dose recommendations are possibleLabel. Apixaban is not recommended for patients with severe hepatic impairmentLabel.
- 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 Apixaban can be increased when it is combined with Abametapir. Abatacept The metabolism of Apixaban can be increased when combined with Abatacept. Abciximab Apixaban may increase the anticoagulant activities of Abciximab. Abemaciclib Abemaciclib may decrease the excretion rate of Apixaban which could result in a higher serum level. Abiraterone The metabolism of Apixaban can be decreased when combined with Abiraterone. - Food Interactions
- Avoid grapefruit products.
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
- Avoid St. John's Wort. St. John's Wort will decrease levels of this medication.
- 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.- Product Images
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apixaban Tablet 5 mg Oral Sivem Pharmaceuticals Ulc 2022-11-01 Not applicable Canada 
Apixaban Tablet 5 mg Oral Sanis Health Inc Not applicable Not applicable Canada Apixaban Tablet 2.5 mg Oral Sivem Pharmaceuticals Ulc 2022-11-01 Not applicable Canada Apixaban Tablet 2.5 mg Oral Sanis Health Inc Not applicable Not applicable Canada Apixaban Accord Tablet 5 mg Oral Accord Healthcare S.L.U. 2021-02-08 Not applicable EU 
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ach-apixaban Tablet 2.5 mg Oral Accord Healthcare Inc 2022-09-27 Not applicable Canada Ach-apixaban Tablet 5 mg Oral Accord Healthcare Inc 2022-09-27 Not applicable Canada Ag-apixaban Tablet 2.5 mg Oral Angita Pharma Inc. 2022-10-28 Not applicable Canada Ag-apixaban Tablet 5 mg Oral Angita Pharma Inc. 2022-10-28 Not applicable Canada Apixaban Tablet, film coated 5 mg/1 Oral Indoco Remedies Limited 2020-09-16 Not applicable US 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image ELIQUIS 30-Day Starter Pack Apixaban (5 mg/1) + Apixaban (5 mg/1) Kit; Tablet, coated Oral E.R. Squibb & Sons, L.L.C. 2017-11-29 Not applicable US ELIQUIS 30-Day Starter Pack Apixaban (5 mg/1) + Apixaban (5 mg/1) Kit; Tablet, coated Oral E.R. Squibb & Sons, L.L.C. 2017-11-29 Not applicable US
Categories
- ATC Codes
- B01AF02 — Apixaban
- Drug Categories
- Anticoagulants
- Antithrombins
- BCRP/ABCG2 Substrates
- Blood and Blood Forming Organs
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Substrates
- Direct factor Xa inhibitors
- Enzyme Inhibitors
- Factor Xa Inhibitors
- Hematologic Agents
- P-glycoprotein substrates
- Protease Inhibitors
- Pyridines
- Serine Protease Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpiperidines. These are compounds containing a phenylpiperidine skeleton, which consists of a piperidine bound to a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Piperidines
- Sub Class
- Phenylpiperidines
- Direct Parent
- Phenylpiperidines
- Alternative Parents
- Phenylpyrazoles / Pyridinecarboxamides / Methoxyanilines / 2-heteroaryl carboxamides / Pyrazole-5-carboxamides / Anisoles / Phenoxy compounds / Methoxybenzenes / Alkyl aryl ethers / Delta lactams show 10 more
- Substituents
- 2-heteroaryl carboxamide / Alkyl aryl ether / Anisole / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid derivative show 24 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- aromatic ether, lactam, piperidones, pyrazolopyridine (CHEBI:72296)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 3Z9Y7UWC1J
- CAS number
- 503612-47-3
- InChI Key
- QNZCBYKSOIHPEH-UHFFFAOYSA-N
- InChI
- InChI=1S/C25H25N5O4/c1-34-19-11-9-18(10-12-19)30-23-20(22(27-30)24(26)32)13-15-29(25(23)33)17-7-5-16(6-8-17)28-14-3-2-4-21(28)31/h5-12H,2-4,13-15H2,1H3,(H2,26,32)
- IUPAC Name
- 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxopiperidin-1-yl)phenyl]-1H,4H,5H,6H,7H-pyrazolo[3,4-c]pyridine-3-carboxamide
- SMILES
- COC1=CC=C(C=C1)N1N=C(C(N)=O)C2=C1C(=O)N(CC2)C1=CC=C(C=C1)N1CCCCC1=O
References
- General References
- Raghavan N, Frost CE, Yu Z, He K, Zhang H, Humphreys WG, Pinto D, Chen S, Bonacorsi S, Wong PC, Zhang D: Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos. 2009 Jan;37(1):74-81. doi: 10.1124/dmd.108.023143. Epub 2008 Oct 2. [Article]
- Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L: Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. doi: 10.1056/NEJMoa1107039. Epub 2011 Aug 27. [Article]
- FDA Drug Approval Package: Apixaban [Link]
- External Links
- KEGG Drug
- D03213
- PubChem Compound
- 10182969
- PubChem Substance
- 175427077
- ChemSpider
- 8358471
- BindingDB
- 19023
- 1364430
- ChEBI
- 72296
- ChEMBL
- CHEMBL231779
- ZINC
- ZINC000011677837
- PharmGKB
- PA166163740
- PDBe Ligand
- GG2
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Apixaban
- PDB Entries
- 2p16 / 6w70 / 8jh6
- FDA label
- Download (926 KB)
- MSDS
- Download (52.4 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 Active Not Recruiting Not Available Atrial Fibrillation 3 somestatus stop reason just information to hide Not Available Active Not Recruiting Treatment Atrial Fibrillation / Stroke, Acute 1 somestatus stop reason just information to hide Not Available Active Not Recruiting Treatment Type 2 Myocardial Infarction 1 somestatus stop reason just information to hide Not Available Completed Not Available Anticoagulant Therapy / Atrial Fibrillation / Obesity 1 somestatus stop reason just information to hide Not Available Completed Not Available Anticoagulants and Bleeding Disorders / Venous Thromboembolism 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 2.5 mg Tablet, film coated Oral 5 mg Tablet, film coated Oral Tablet Oral 2.5 mg Tablet Oral 5 mg Tablet, film coated Oral 2.5 mg/1 Tablet, film coated Oral 5 mg/1 Tablet, coated Oral 2.5 mg Kit; tablet, coated Oral Tablet Oral 5.000 mg Tablet Oral 2.500 mg Tablet, coated Oral 5 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA2349330 No 2009-09-29 2019-12-17 Canada CA2461202 No 2011-07-12 2022-09-17 Canada US6413980 No 2002-07-02 2019-12-22 US US6967208 No 2005-11-22 2023-02-03 US US9326945 No 2016-05-03 2031-02-24 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 326.53 [MSDS] boiling point (°C) 770.5 [MSDS] water solubility 0.11mg/mL http://www.chemspider.com/Chemical-Structure.8358471.html?rid=2f601343-f676-4fcd-ad7d-1151c737876f logP 2.71 [MSDS] - Predicted Properties
Property Value Source Water Solubility 0.0679 mg/mL ALOGPS logP 2.22 ALOGPS logP 1.83 Chemaxon logS -3.8 ALOGPS pKa (Strongest Acidic) 13.07 Chemaxon pKa (Strongest Basic) -1.6 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 110.76 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 126.9 m3·mol-1 Chemaxon Polarizability 49.74 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9974 Blood Brain Barrier + 0.9329 Caco-2 permeable - 0.5308 P-glycoprotein substrate Substrate 0.6144 P-glycoprotein inhibitor I Inhibitor 0.6804 P-glycoprotein inhibitor II Inhibitor 0.594 Renal organic cation transporter Non-inhibitor 0.5628 CYP450 2C9 substrate Non-substrate 0.8528 CYP450 2D6 substrate Non-substrate 0.811 CYP450 3A4 substrate Substrate 0.764 CYP450 1A2 substrate Non-inhibitor 0.9271 CYP450 2C9 inhibitor Inhibitor 0.5555 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.5 CYP450 3A4 inhibitor Inhibitor 0.5 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6447 Ames test Non AMES toxic 0.5062 Carcinogenicity Non-carcinogens 0.8796 Biodegradation Not ready biodegradable 0.9965 Rat acute toxicity 2.3038 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8351 hERG inhibition (predictor II) Inhibitor 0.6205
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 238.9257875 predictedDarkChem Lite v0.1.0 [M-H]- 213.47229 predictedDeepCCS 1.0 (2019) [M+H]+ 239.1317875 predictedDarkChem Lite v0.1.0 [M+H]+ 215.86786 predictedDeepCCS 1.0 (2019) [M+Na]+ 238.4341875 predictedDarkChem Lite v0.1.0 [M+Na]+ 221.78038 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting. Factor Xa activates pro-inflammatory signaling pathways in a protease-activated receptor (PAR)-dependent manner (PubMed:24041930, PubMed:30568593, PubMed:34831181). Up-regulates expression of protease-activated receptors (PARs) F2R, F2RL1 and F2RL2 in dermal microvascular endothelial cells (PubMed:35738824). Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2 and IL6, in cardiac fibroblasts and umbilical vein endothelial cells in PAR-1 (F2R)-dependent manner (PubMed:30568593, PubMed:34831181). Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2, IL6, TNF-alpha/TNF, IL-1beta/IL1B, IL8/CXCL8 and IL18, in endothelial cells and atrial tissues (PubMed:24041930, PubMed:35738824, PubMed:9780208). Induces expression of adhesion molecules, such as ICAM1, VCAM1 and SELE, in endothelial cells and atrial tissues (PubMed:24041930, PubMed:35738824, PubMed:9780208). Increases expression of phosphorylated ERK1/2 in dermal microvascular endothelial cells and atrial tissues (PubMed:24041930, PubMed:35738824). Triggers activation of the transcription factor NF-kappa-B in dermal microvascular endothelial cells and atrial tissues (PubMed:24041930, PubMed:35738824). Up-regulates expression of plasminogen activator inhibitor 1 (SERPINE1) in atrial tissues (PubMed:24041930)
- Specific Function
- Calcium ion binding
- Gene Name
- F10
- Uniprot ID
- P00742
- Uniprot Name
- Coagulation factor X
- Molecular Weight
- 54731.255 Da
References
- Spyropoulos AC: Investigational treatments of venous thromboembolism. Expert Opin Investig Drugs. 2007 Apr;16(4):431-40. [Article]
- Harenberg J, Wehling M: Current and future prospects for anticoagulant therapy: inhibitors of factor Xa and factor IIa. Semin Thromb Hemost. 2008 Feb;34(1):39-57. doi: 10.1055/s-2008-1066023. [Article]
- 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 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
- Wang L, Zhang D, Raghavan N, Yao M, Ma L, Frost CE, Maxwell BD, Chen SY, He K, Goosen TC, Humphreys WG, Grossman SJ: In vitro assessment of metabolic drug-drug interaction potential of apixaban through cytochrome P450 phenotyping, inhibition, and induction studies. Drug Metab Dispos. 2010 Mar;38(3):448-58. doi: 10.1124/dmd.109.029694. Epub 2009 Nov 25. [Article]
- Apixaban FDA label [File]
- 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, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). 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:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- Aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
References
- 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, 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
- 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
- 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
- Cada DJ, Levien TL, Baker DE: Apixaban. Hosp Pharm. 2013 Jun;48(6):494-509. doi: 10.1310/hpj4806-494. [Article]
- Budovich A, Zargarova O, Nogid A: Role of apixaban (eliquis) in the treatment and prevention of thromboembolic disease. P T. 2013 Apr;38(4):206-31. [Article]
- Wu Z, Lee D, Joo J, Shin JH, Kang W, Oh S, Lee do Y, Lee SJ, Yea SS, Lee HS, Lee T, Liu KH: CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of albendazole and fenbendazole in human liver microsomes and recombinant P450 assay systems. Antimicrob Agents Chemother. 2013 Nov;57(11):5448-56. doi: 10.1128/AAC.00843-13. Epub 2013 Aug 19. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) in the cardiovascular system (PubMed:19965576, PubMed:8631948). 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:19965576, PubMed:8631948). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:8631948). Converts arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EpETrE), likely playing a major role in the epoxidation of endogenous cardiac arachidonic acid pools (PubMed:8631948). In endothelial cells, participates in eicosanoids metabolism by converting hydroperoxide species into hydroxy epoxy metabolites. In combination with 15-lipoxygenase metabolizes arachidonic acid and converts hydroperoxyicosatetraenoates (HpETEs) into hydroxy epoxy eicosatrienoates (HEETs), which are precursors of vasodilatory trihydroxyicosatrienoic acids (THETAs). This hydroperoxide isomerase activity is NADPH- and O2-independent (PubMed:19737933). Catalyzes the monooxygenation of a various xenobiotics, such as danazol, amiodarone, terfenadine, astemizole, thioridazine, tamoxifen, cyclosporin A and nabumetone (PubMed:19923256). Catalyzes hydroxylation of the anthelmintics albendazole and fenbendazole (PubMed:23959307). Catalyzes the sulfoxidation of fenbedazole (PubMed:19923256)
- Specific Function
- Arachidonic acid 11,12-epoxygenase activity
- Gene Name
- CYP2J2
- Uniprot ID
- P51589
- Uniprot Name
- Cytochrome P450 2J2
- Molecular Weight
- 57610.165 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). 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:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion 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 all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
- Specific Function
- Aromatase activity
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Authors unspecified: Apixaban. After hip or knee replacement: LMWH remains the standard treatment. Prescrire Int. 2012 Sep;21(130):201-2, 204. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- Abc-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
References
- Heyes N, Kapoor P, Kerr ID: Polymorphisms of the Multidrug Pump ABCG2: A Systematic Review of Their Effect on Protein Expression, Function, and Drug Pharmacokinetics. Drug Metab Dispos. 2018 Dec;46(12):1886-1899. doi: 10.1124/dmd.118.083030. Epub 2018 Sep 28. [Article]
Drug created at March 19, 2008 16:40 / Updated at September 15, 2024 01:12