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Identification
- Summary
Acenocoumarol is an anticoagulant drug used in the prevention of thromboembolic diseases in infarction and transient ischemic attacks, as well as management of deep vein thrombosis and myocardial infarction.
- Generic Name
- Acenocoumarol
- DrugBank Accession Number
- DB01418
- Background
Acenocoumarol is a coumarin derivative used as an anticoagulant. Coumarin derivatives inhibit the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of vitamin K-dependent clotting factors, II, VII, IX and X, and interferes with coagulation.6 Hematocrit, hemoglobin, international normalized ratio and liver panel should be monitored. Patients on acenocoumarol are prohibited from giving blood.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Acenocoumarol (DB01418)
- Weight
- Average: 353.3255
Monoisotopic: 353.089937217 - Chemical Formula
- C19H15NO6
- Synonyms
- 3-(alpha-(4'-Nitrophenyl)-beta-acetylethyl)-4-hydroxycoumarin
- 3-(alpha-(p-Nitrophenol)-beta-acetylethyl)-4-hydroxycoumarin
- 3-(alpha-Acetonyl-4-nitrobenzyl)-4-hydroxycoumarin
- 3-(alpha-Acetonyl-p-nitrobenzyl)-4-hydroxycoumarin
- 3-(alpha-p-Nitrophenyl-beta-acetylethyl)-4-hydroxycoumarin
- 4-Hydroxy-3-(1-(4-nitrophenyl)-3-oxobutyl)-2H-1-benzopyran-2-one
- 4-Hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-one
- Acenocoumarin
- Acénocoumarol
- Acenocoumarol
- Acenocoumarolum
- Acenocumarol
- Acenocumarolo
- Acenokumarin
- Nicoumalone
- Nicumalon
- Nitrophenylacetylethyl-4-hydroxycoumarine
- Nitrovarfarian
- Nitrowarfarin
Pharmacology
- Indication
For the treatment and prevention of thromboembolic diseases. More specifically, it is indicated for the prevention of cerebral embolism, deep vein thrombosis, pulmonary embolism, thromboembolism in infarction and transient ischemic attacks. It is used for the treatment of deep vein thrombosis and myocardial infarction.
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 Adjunct therapy in treatment of Coronary occlusion •••••••••••• Treatment of Embolism •••••••••••• Prophylaxis of Pulmonary embolism •••••••••••• Treatment of Pulmonary embolism •••••••••••• Adjunct therapy in treatment of Transient ischemic attack •••••••••••• - 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
Acenocoumarol inhibits the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of certain glutamic acid residues near the N-terminals of clotting factors II, VII, IX and X, the vitamin K-dependent clotting factors. Glutamic acid carboxylation is important for the interaction between these clotting factors and calcium. Without this interaction, clotting cannot occur. Both the extrinsic (via factors VII, X and II) and intrinsic (via factors IX, X and II) are affected by acenocoumarol.
- Mechanism of action
Acenocoumarol inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent clotting factors, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited resulting in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.
Target Actions Organism AVitamin K epoxide reductase complex subunit 1 inhibitorHumans - Absorption
Rapidly absorbed orally with greater than 60% bioavailability. Peak plasma levels are attained 1 to 3 hours following oral administration.
- Volume of distribution
The volume of distribution at steady-state appeared to be significantly dose dependent: 78 ml/kg for doses < or = 20 microg/kg and 88 ml/kg for doses > 20 microg/kg respectively
- Protein binding
98.7% protein bound, mainly to albumin
- Metabolism
Extensively metabolized in the liver via oxidation forming two hydroxy metabolites and keto reduction producing two alcohol metabolites. Reduction of the nitro group produces an amino metabolite which is further transformed to an acetoamido metabolite. Metabolites do not appear to be pharmacologically active.
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- Route of elimination
Mostly via the kidney as metabolites
- Half-life
8 to 11 hours.
- Clearance
Not Available
- 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 onset and severity of the symptoms are dependent on the individual's sensitivity to oral anticoagulants, the severity of the overdosage, and the duration of treatment. Bleeding is the major sign of toxicity with oral anticoagulant drugs. The most frequent symptoms observed are: cutaneous bleeding (80%), haematuria (with renal colic) (52%), haematomas, gastrointestinal bleeding, haematemesis, uterine bleeding, epistaxis, gingival bleeding and bleeding into the joints. Further symptoms include tachycardia, hypotension, peripheral circulatory disorders due to loss of blood, nausea, vomiting, diarrhoea and abdominal pains.
- Pathways
Pathway Category Acenocoumarol Action Pathway Drug action - Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 2C9 CYP2C9*2 (T;T) / (C;T) T Allele Effect Directly Studied The presence of this polymorphism in CYP2C9 is associated with reduction in acenocoumarol metabolism. Details Cytochrome P450 2C9 CYP2C9*3 (C;C) / (A;C) C Allele Effect Directly Studied The presence of this polymorphism in CYP2C9 is associated with reduction in acenocoumarol metabolism. Details Vitamin K epoxide reductase complex subunit 1 --- (A;A) / (A;G) G > A ADR Directly Studied The presence of this single nucleotide polymorphism in VKORC1 is associated with reduction in acenocoumarol metabolism and increased risk of drug-related hemorrhage. Details Cytochrome P450 2C9 CYP2C9*2 (T;T) / (C;T) T Allele Effect Directly Studied Patients with this polymorphism in CYP2C9 may be at a higher risk of developing drug-related hemorrhage or thrombosis when treated with acenocoumarol. Details Cytochrome P450 2C9 CYP2C9*3 (C;C) / (A;C) C Allele Effect Directly Studied Patients with this polymorphism in CYP2C9 may be at a higher risk of developing drug-related hemorrhage or thrombosis when treated with acenocoumarol. Details Cytochrome P450 2C9 CYP2C9*6 Not Available 818delA Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Cytochrome P450 2C9 CYP2C9*15 Not Available 485C>A Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Cytochrome P450 2C9 CYP2C9*25 Not Available 353_362delAGAAATGGAA Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Cytochrome P450 2C9 CYP2C9*35 Not Available 374G>T / 430C>T Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Cytochrome P450 2C9 CYP2C9*4 Not Available 1076T>C Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Cytochrome P450 2C9 CYP2C9*5 Not Available 1080C>G Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Cytochrome P450 2C9 CYP2C9*8 Not Available 449G>A Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Cytochrome P450 2C9 CYP2C9*11 Not Available 1003C>T Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Cytochrome P450 2C9 CYP2C9*12 Not Available 1465C>T Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Cytochrome P450 2C9 CYP2C9*13 Not Available 269T>C Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Cytochrome P450 2C9 CYP2C9*14 Not Available 374G>A Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Cytochrome P450 2C9 CYP2C9*16 Not Available 895A>G Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Cytochrome P450 2C9 CYP2C9*18 Not Available 1075A>C / 1190A>C … show all Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Cytochrome P450 2C9 CYP2C9*26 Not Available 389C>G Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Cytochrome P450 2C9 CYP2C9*28 Not Available 641A>T Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Cytochrome P450 2C9 CYP2C9*30 Not Available 1429G>A Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Cytochrome P450 2C9 CYP2C9*33 Not Available 395G>A Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details
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 Acenocoumarol can be increased when it is combined with Abametapir. Abatacept The metabolism of Acenocoumarol can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Acenocoumarol. Abiraterone The serum concentration of Acenocoumarol can be increased when it is combined with Abiraterone. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Acenocoumarol. - Food Interactions
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
- Ensure consistent Vitamin K intake. Changes in vitamin K intake may impact coagulation. Foods containing vitamin K include spinach, kale, and swiss chard.
- Exercise caution with St. John's Wort.
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.- International/Other Brands
- Ascumar (Star) / Mini-sintrom
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Sintrom Tablet 1 mg Oral Paladin Labs Inc. 1962-12-31 2021-09-02 Canada 
Sintrom Tablet 4 mg Oral Paladin Labs Inc. 1957-12-31 2021-09-02 Canada Truemed Group LLC Tablet 4 mg/1 Oral Truemed Group LLC 2022-09-17 Not applicable US 
Categories
- ATC Codes
- B01AA07 — Acenocoumarol
- Drug Categories
- 4-Hydroxycoumarins
- Anticoagulants
- Benzopyrans
- Blood and Blood Forming Organs
- Coumarins
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Substrates
- Hematologic Agents
- Heterocyclic Compounds, Fused-Ring
- Narrow Therapeutic Index Drugs
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Pyrans
- Vitamin K Antagonists
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 4-hydroxycoumarins. These are coumarins that contain one or more hydroxyl groups attached to C4-position the coumarin skeleton.
- Kingdom
- Organic compounds
- Super Class
- Phenylpropanoids and polyketides
- Class
- Coumarins and derivatives
- Sub Class
- Hydroxycoumarins
- Direct Parent
- 4-hydroxycoumarins
- Alternative Parents
- 1-benzopyrans / Nitrobenzenes / Nitroaromatic compounds / Pyranones and derivatives / Vinylogous acids / Heteroaromatic compounds / Lactones / Ketones / Propargyl-type 1,3-dipolar organic compounds / Oxacyclic compounds show 5 more
- Substituents
- 1-benzopyran / 4-hydroxycoumarin / Allyl-type 1,3-dipolar organic compound / Aromatic heteropolycyclic compound / Benzenoid / Benzopyran / C-nitro compound / Carbonyl group / Heteroaromatic compound / Hydrocarbon derivative show 20 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- C-nitro compound, methyl ketone, hydroxycoumarin (CHEBI:53766)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- I6WP63U32H
- CAS number
- 152-72-7
- InChI Key
- VABCILAOYCMVPS-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H15NO6/c1-11(21)10-15(12-6-8-13(9-7-12)20(24)25)17-18(22)14-4-2-3-5-16(14)26-19(17)23/h2-9,15,22H,10H2,1H3
- IUPAC Name
- 4-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-one
- SMILES
- CC(=O)CC(C1=CC=C(C=C1)[N+]([O-])=O)C1=C(O)C2=CC=CC=C2OC1=O
References
- Synthesis Reference
Stoll, W. and Litvan, F.; U.S. Patent 2,648,682; August 11,1953; assigned to J.R. Geigy A.G., Switzerland.
- General References
- Cesar JM, Garcia-Avello A, Navarro JL, Herraez MV: Aging and oral anticoagulant therapy using acenocoumarol. Blood Coagul Fibrinolysis. 2004 Oct;15(8):673-6. [Article]
- Lengyel M: [Warfarin or acenocoumarol is better in the anticoagulant treatment of chronic atrial fibrillation?]. Orv Hetil. 2004 Dec 26;145(52):2619-21. [Article]
- Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [Article]
- Montes R, Ruiz de Gaona E, Martinez-Gonzalez MA, Alberca I, Hermida J: The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients. Br J Haematol. 2006 Apr;133(2):183-7. [Article]
- Girard P, Nony P, Erhardtsen E, Delair S, Ffrench P, Dechavanne M, Boissel JP: Population pharmacokinetics of recombinant factor VIIa in volunteers anticoagulated with acenocoumarol. Thromb Haemost. 1998 Jul;80(1):109-13. [Article]
- Danziger J: Vitamin K-dependent proteins, warfarin, and vascular calcification. Clin J Am Soc Nephrol. 2008 Sep;3(5):1504-10. doi: 10.2215/CJN.00770208. Epub 2008 May 21. [Article]
- External Links
- Human Metabolome Database
- HMDB0015487
- KEGG Drug
- D07064
- PubChem Compound
- 54676537
- PubChem Substance
- 46507631
- ChemSpider
- 10443441
- 154
- ChEBI
- 53766
- ChEMBL
- CHEMBL397420
- Therapeutic Targets Database
- DAP000772
- PharmGKB
- PA452632
- Wikipedia
- Acenocoumarol
- MSDS
- Download (126 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Atrial Fibrillation 2 somestatus stop reason just information to hide Not Available Completed Not Available Atrial Fibrillation or Flutter 1 somestatus stop reason just information to hide Not Available Completed Not Available Pulmonary Arterial Hypertension (PAH) 1 somestatus stop reason just information to hide Not Available Completed Not Available Unsuspected Pulmonary Embolism 1 somestatus stop reason just information to hide Not Available Completed Treatment Healthy Volunteers (HV) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 4.000 mg Tablet Oral 1 mg Tablet Oral 4 mg Tablet Oral 4 mg/1 - Prices
Unit description Cost Unit Sintrom 4 mg Tablet 1.6USD tablet Sintrom 1 mg Tablet 0.51USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 196-199 Merck Index 23 water solubility practically insoluble MSDS logP 1.98 SANGSTER (1994) - Predicted Properties
Property Value Source Water Solubility 0.0106 mg/mL ALOGPS logP 2.53 ALOGPS logP 2.68 Chemaxon logS -4.5 ALOGPS pKa (Strongest Acidic) 5.09 Chemaxon pKa (Strongest Basic) -6.9 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 106.74 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 93.18 m3·mol-1 Chemaxon Polarizability 34.44 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 No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.7518 Blood Brain Barrier + 0.5765 Caco-2 permeable + 0.5 P-glycoprotein substrate Non-substrate 0.6031 P-glycoprotein inhibitor I Non-inhibitor 0.7078 P-glycoprotein inhibitor II Non-inhibitor 0.843 Renal organic cation transporter Non-inhibitor 0.8944 CYP450 2C9 substrate Non-substrate 0.6256 CYP450 2D6 substrate Non-substrate 0.8936 CYP450 3A4 substrate Substrate 0.6267 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Inhibitor 0.8949 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.831 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7492 Ames test AMES toxic 0.6954 Carcinogenicity Non-carcinogens 0.7015 Biodegradation Not ready biodegradable 0.9403 Rat acute toxicity 2.7869 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.6326 hERG inhibition (predictor II) Non-inhibitor 0.9347
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0005-4394000000-cee5104d5911648240f0 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 199.1147629 predictedDarkChem Lite v0.1.0 [M-H]- 180.42104 predictedDeepCCS 1.0 (2019) [M+H]+ 198.6442629 predictedDarkChem Lite v0.1.0 [M+H]+ 182.77904 predictedDeepCCS 1.0 (2019) [M+Na]+ 199.4330629 predictedDarkChem Lite v0.1.0 [M+Na]+ 189.85472 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the gamma-carboxylation of various proteins, including clotting factors, and is required for normal blood coagulation, but also for normal bone development
- Specific Function
- quinone binding
- Gene Name
- VKORC1
- Uniprot ID
- Q9BQB6
- Uniprot Name
- Vitamin K epoxide reductase complex subunit 1
- Molecular Weight
- 18234.3 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Bodin L, Verstuyft C, Tregouet DA, Robert A, Dubert L, Funck-Brentano C, Jaillon P, Beaune P, Laurent-Puig P, Becquemont L, Loriot MA: Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity. Blood. 2005 Jul 1;106(1):135-40. Epub 2005 Mar 24. [Article]
- Gonzalez-Conejero R, Corral J, Roldan V, Ferrer F, Sanchez-Serrano I, Sanchez-Blanco JJ, Marin F, Vicente V: The genetic interaction between VKORC1 c1173t and calumenin a29809g modulates the anticoagulant response of acenocoumarol. J Thromb Haemost. 2007 Aug;5(8):1701-6. Epub 2007 May 21. [Article]
- Montes R, Ruiz de Gaona E, Martinez-Gonzalez MA, Alberca I, Hermida J: The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients. Br J Haematol. 2006 Apr;133(2):183-7. [Article]
- Rettie AE, Farin FM, Beri NG, Srinouanprachanh SL, Rieder MJ, Thijssen HH: A case study of acenocoumarol sensitivity and genotype-phenotype discordancy explained by combinations of polymorphisms in VKORC1 and CYP2C9. Br J Clin Pharmacol. 2006 Nov;62(5):617-20. Epub 2006 Jul 21. [Article]
- Schalekamp T, Brasse BP, Roijers JF, Chahid Y, van Geest-Daalderop JH, de Vries-Goldschmeding H, van Wijk EM, Egberts AC, de Boer A: VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects overanticoagulation. Clin Pharmacol Ther. 2006 Jul;80(1):13-22. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [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
- 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
- Saraeva RB, Paskaleva ID, Doncheva E, Eap CB, Ganev VS: Pharmacogenetics of acenocoumarol: CYP2C9, CYP2C19, CYP1A2, CYP3A4, CYP3A5 and ABCB1 gene polymorphisms and dose requirements. J Clin Pharm Ther. 2007 Dec;32(6):641-9. [Article]
- Thijssen HH, Ritzen B: Acenocoumarol pharmacokinetics in relation to cytochrome P450 2C9 genotype. Clin Pharmacol Ther. 2003 Jul;74(1):61-8. doi: 10.1016/S0009-9236(03)00088-2. [Article]
- 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
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Saraeva RB, Paskaleva ID, Doncheva E, Eap CB, Ganev VS: Pharmacogenetics of acenocoumarol: CYP2C9, CYP2C19, CYP1A2, CYP3A4, CYP3A5 and ABCB1 gene polymorphisms and dose requirements. J Clin Pharm Ther. 2007 Dec;32(6):641-9. [Article]
- Acenocoumarol monograph [File]
- 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
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Saraeva RB, Paskaleva ID, Doncheva E, Eap CB, Ganev VS: Pharmacogenetics of acenocoumarol: CYP2C9, CYP2C19, CYP1A2, CYP3A4, CYP3A5 and ABCB1 gene polymorphisms and dose requirements. J Clin Pharm Ther. 2007 Dec;32(6):641-9. [Article]
- Acenocoumarol monograph [File]
- 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
- Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [Article]
- Morales-Molina JA, Arrebola MA, Robles PA, Mangana JC: Possible interaction between topical terbinafine and acenocoumarol. Ann Pharmacother. 2009 Nov;43(11):1911-2. doi: 10.1345/aph.1M299. Epub 2009 Oct 20. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Fitos I, Visy J, Simonyi M, Hermansson J: Stereoselective distribution of acenocoumarol enantiomers in human plasma: chiral chromatographic analysis of the ultrafiltrates. Chirality. 1993;5(5):346-9. [Article]
- Fitos I, Visy J, Magyar A, Kajtar J, Simonyi M: Inverse stereoselectivity in the binding of acenocoumarol to human serum albumin and to alpha 1-acid glycoprotein. Biochem Pharmacol. 1989 Jul 15;38(14):2259-62. [Article]
- Otagiri M, Fleitman JS, Perrin JH: Investigations into the binding of phenprocoumon to albumin using fluorescence spectroscopy. J Pharm Pharmacol. 1980 Jul;32(7):478-82. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- General Function
- Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
- Specific Function
- Not Available
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23539.43 Da
References
- Fitos I, Visy J, Simonyi M, Hermansson J: Stereoselective distribution of acenocoumarol enantiomers in human plasma: chiral chromatographic analysis of the ultrafiltrates. Chirality. 1993;5(5):346-9. [Article]
- Fitos I, Visy J, Magyar A, Kajtar J, Simonyi M: Inverse stereoselectivity in the binding of acenocoumarol to human serum albumin and to alpha 1-acid glycoprotein. Biochem Pharmacol. 1989 Jul 15;38(14):2259-62. [Article]
- Hazai E, Visy J, Fitos I, Bikadi Z, Simonyi M: Selective binding of coumarin enantiomers to human alpha1-acid glycoprotein genetic variants. Bioorg Med Chem. 2006 Mar 15;14(6):1959-65. Epub 2005 Nov 15. [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
- Saraeva RB, Paskaleva ID, Doncheva E, Eap CB, Ganev VS: Pharmacogenetics of acenocoumarol: CYP2C9, CYP2C19, CYP1A2, CYP3A4, CYP3A5 and ABCB1 gene polymorphisms and dose requirements. J Clin Pharm Ther. 2007 Dec;32(6):641-9. [Article]
Drug created at July 24, 2007 08:32 / Updated at October 17, 2024 13:59