General
Preferred name
WARFARIN
Synonyms
WARF42 ()
Athrombine-K ()
WARFARIN SODIUM ()
WARFARIN SODIUM129-06-6 ()
NSC-59813 ()
Warfarine ()
Warfarina ()
Athrombin ()
Marevan ()
Coumadin ()
Apo-warfarin ()
Sodium warfarin ()
Warfarin sodium salt ()
Prothromadin ()
Jantoven ()
Panwarfin ()
Aldocumar ()
Zoocoumarin sodium salt ()
Warfarinum natricum ()
Athrombin-K ()
Warfarin-potassium ()
Potassium warfarin ()
WARFARIN POTASSIUM ()
(?)-Warfarin ()
(?)-Warfarin-d5 ()
P&D ID
PD001720
CAS
81-81-2
129-06-6
5543-79-3
36508-91-5
12795-55-0
2610-86-8
75472-93-4
Tags
available
drug
Approved by
FDA
First approval
1954
1982
Drug indication
Atrial fibrillation
Anticoagulant
Thrombosis
Drug Status
approved
Max Phase
4.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
ROE
The elimination of warfarin is almost entirely by metabolism with a small amount excreted unchanged.[label,L6616,A2460] 80% of the total dose is excreted in the urine with the remaining 20% appearing in the feces.[A2460]
MOA
Warfarin is a [vitamin K] antagonist which acts to inhibit the production of vitamin K by vitamin K epoxide reductase.[label,A179221,T116] The reduced form of vitamin K, vitamin KH2 is a cofactor used in the γ-carboxylation of coagulation factors VII, IX, X, and thrombin. Carboxylation induces a conformational change allowing the factors to bind Ca2+ and to phospholipid surfaces. Uncarboxylated factors VII, IX, X, and thrombin are biologically inactive and therefore serve to interrupt the coagulation cascade. The endogenous anticoagulation proteins C and S also require γ-carboxylation to function. This is particularly true in the case of thrombin which must be activated in order to form a thrombus. vitamin KH2 is converted to vitamin K epoxide as part of the γ-carboxylation reaction catalyzed by γ-glutamyl carboxylase. Vitamin K epoxide is then converted to vitamin K1 by vitamin K epoxide reductase then back to vitamin KH2 by vitamin K reductase. Warfarin binds to vitamin K epoxide reductase complex subunit 1 and irreversibly inhibits the enzyme thereby stopping the recycling of vitamin K by preventing the conversion of vitamin K epoxide to vitamin K1. This process creates a hypercoagulable state for a short time as proteins C and S degrade first with half lives of 8 and 24 hours, with the exception of factor VII which has a half life of 6 hours.[A179221] Factors IX, X, and finally thrombin degrade later with half lives of 24, 36, and 50 hours resulting in a dominant anticoagulation effect.[A179221] In order to reverse this anticoagulation vitamin K must be supplied, either exogenously or by removal of the vitamin K epoxide reductase inhibition, and time allowed for new coagulation factors to be synthesized.[label,A179221,T116] It takes approximately 2 days for new coagulation factors to be synthesized in the liver. Vitamin K2, functionally identical to vitamin K1, is synthesized by gut bacteria leading to interactions with antibiotics as elimination of these bacteria can reduce vitamin K2
INDICATION
**Indicated** for:[label,L6616]; ; 1) Prophylaxis and treatment of venous thromboembolism and related pulmonary embolism.; ; 2) Prophylaxis and treatment of thromboembolism associated with atrial fibrillation.; ; 3) Prophylaxis and treatment of thromboembolism associated with cardiac valve replacement.; ; 4) Use as adjunct therapy to reduce mortality, recurrent myocardial infarction, and thromboembolic events post myocardial infarction.; ; **Off-label** uses include:; ; 1) Secondary prevention of stroke and transient ischemic attacks in patients with rheumatic mitral valve disease but without atrial fibrillation.[A179182]
HALF-LIFE
R-warfarin is cleared more slowly than S-warfarin, at about half the rate.[label] T1/2 for R-warfarin is 37-89 hours. T1/2 for S-warfarin is 21-43 hours.
METABOLISM
Metabolism of warfarin is both stereo- and regio-selective.[A2460] The major metabolic pathway is oxidation to various hydroxywarfarins, comprising 80-85% of the total metabolites. CYP2C9 is the major enzyme catalyzing the 6- and 7-hydroxylation of S-warfarin while 4'-hydroxylation occurs through CYP2C18 with minor contributions from CYP2C19. R-warfarin is metabolized to 4'-hydroxywarfarin by CYP2C8 with some contirbuting by CYP2C19, 6- and 8-hydroxywarfarin by CYP1A2 and CYP2C19, 7-hydroxywarfarin by CYP1A2 and CYP2C8, and lastly to 10-hydroxywarfarin by CYP3A4. The 10-hydroxywarfarin metabolite as well as a benzylic alcohol metabolite undergo an elimination step to form dehydrowarfarin. The minor pathway of metabolism is the reduction of the ketone group to warfarin alcohols, comprising 20% of the metabolites. Limited conjugation occurs with sulfate and gluronic acid groups but these metabolites have only been confirmed for R-hydroxywarfarins.
ABSORPTION
Completely absorbed from the GI tract. The mean Tmax for warfarin sodium tablets is 4 hours.[label,L6616,A2460]
DESCRIPTION
PubChem CID 54678486 is an enatiomeric mixture of the much more active S-form (CID 54688261) and the R-form (CID 54684598) . This reference also reviews important pharmacogenomic aspects of this drug but note the application of this has become controversial (see the PharmKB drug link). Note also there is also a tautomeric variant depicted as CID 54689812. Marketed formulations may specify warfarin sodium (CID 16204922) or warfarin potassium (CID 23706212).
(GtoPdb)
DESCRIPTION
Warfarin is an anticoagulant applicated in the prevention of thrombosis and thromboembolism, the formation of blood clots in the blood vessels and their migration elsewhere in the body. Warfarin was approved for use as a medication in 1954, and has remained popular ever since
(BOC Sciences Bioactive Compounds)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
1
Organisms
0
Compound Sets
21
BOC Sciences Bioactive Compounds
ChEMBL Approved Drugs
ChEMBL Drugs
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Enamine BioReference Compounds
Guide to Pharmacology
Mcule NIBR MoA Box Subset
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
Prestwick Chemical Library
ReFrame library
TargetMol Bioactive Compound Library
The Spectrum Collection
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
86
Molecular Weight
308.1
Hydrogen Bond Acceptors
4
Hydrogen Bond Donors
1
Rotatable Bonds
4
Ring Count
3
Aromatic Ring Count
3
cLogP
3.61
TPSA
67.51
Fraction CSP3
0.16
Chiral centers
1.0
Largest ring
6.0
QED
0.75
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
Metabolism
Target
VKOR complex subunit 1
MOA
Vitamin inhibitor
Vitamin K Epoxide Reductase (VKER, VKOR) Inhibitors
Member status
member
Therapeutic Class
Anticoagulants
Solubility
Soluble in DMSO
Source data
