Tmic
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Record Information
Version2.0
Creation Date2009-07-05 03:18:12 UTC
Update Date2014-12-24 20:25:42 UTC
Accession NumberT3D2567
Identification
Common NameWarfarin
ClassSmall Molecule
DescriptionWarfarin is an anticoagulant drug normally used to prevent blood clot formation as well as migration. Although originally marketed as a pesticide (d-Con, Rodex, among others), Warfarin has since become the most frequently prescribed oral anticoagulant in North America. Warfarin has several properties that should be noted when used medicinally, including its ability to cross the placental barrier during pregnancy which can result in fetal bleeding, spontaneous abortion, preterm birth, stillbirth, and neonatal death. Additional adverse effects such as necrosis, purple toe syndrome, osteoporosis, valve and artery calcification, and drug interactions have also been documented with warfarin use. Warfarin does not actually affect blood viscosity, rather, it inhibits vitamin-k dependent synthesis of biologically active forms of various clotting factors in addition to several regulatory factors.
Compound Type
  • Anticoagulant
  • Coumarin and Indandione Rodenticide
  • Drug
  • Ester
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Pesticide
  • Rodenticide
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(phenyl-1 acetyl-2 ethyl) 3-hydroxy-4 coumarin
(phenyl-1 acetyl-2 ethyl) 3-hydroxy-4 coumarine
(S)-4-hydroxy-3-(3-oxo-1-phenylbutyl)-2-benzopyrone
1-(4'-Hydroxy-3'-coumarinyl)-1-phenyl-3-butanone
200 Coumarin
3-(1'-Phenyl-2'-acetylethyl)-4-hydroxycoumarin
3-(Acetonylbenzyl)-4-hydroxycoumarin
3-(alpha-Acetonylbenzyl)-4-hydroxycoumarin
3-(alpha-Phenyl-beta-acetylaethyl)-4-hydroxycumarin
3-(alpha-Phenyl-beta-acetylethyl)-4-hydroxycoumarin
4-Hydroxy-3- (3-oxo-1-fenyl-butyl) cumarine
4-Hydroxy-3- (3-oxo-1-phenyl-butyl)-cumarin
4-Hydroxy-3-(3-oxo-1-fenyl-butyl) cumarine
4-Hydroxy-3-(3-oxo-1-phenyl-butyl)-cumarin
4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one
4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-chromen-2-one
4-Hydroxy-3-(3-oxo-1-phenylbutyl)coumarin
4-Idrossi-3- (3-oxo-)-fenil-butil)-cumarine
4-Idrossi-3-(3-oxo-)-fenil-butil)-cumarine
4-Idrossi-3-(3-oxo-1-fenil-butil)-cumarine
4oh-coumarin deriv.
Arab rat death
Arab rat deth
Athrombin-k
Athrombine-k
Brumolin
Co-rax
Compound 42
Coumadin
Coumafen
Coumafene
Coumaphen
Coumaphene
Coumarins
Coumefene
Cov-R-tox
D-Con
delta-Con
Dethmor
Dethnel
Dicusat e
DL-3-(alpha-acetonylbenzyl)-4-hydroxycoumarin
Eastern states duocide
Fasco fascrat powder
Frass-ratron
Jantoven
Killgerm sewarin p
Kumader
Kumadu
Kumatox
Kypfarin
Latka 42
Lawarin
Liqua-tox
Maag rattentod cum
Mar-frin
Marevan
Martin'S mar-frin
Maveran
Mouse pak
Place-pax
Prothromadin
Rat & mice bait
Rat and mice bait
Rat-a-way
Rat-alpha-way
Rat-b-gon
Rat-beta-gon
Rat-gard
Rat-kill
Rat-mix
Rat-O-cide #2
Rat-O-cide no. 2
Rat-ola
Rat-trol
Ratorex
Ratox
Ratoxin
Ratron
Ratron g
Rats-no-more
Ratten-koederrohr
Rattenstreupulver neu schacht
Rattenstreupulver new schacht
Rattentraenke
Rattunal
RAX
RCR grey squirrel killer concentrate
Ro-deth
Rodafarin
Rodafarin c
Rodex
Rodex blox
Rosex
Rough & ready mouse mix
Rough and ready mouse mix
Sakarat
Sewarin
Solfarin
Sorexa plus
Spray-trol brand roden-trol
Temus w
Tox-hid
Twin light rat away
Vampirinip II
Vampirinip III
Waran
Warfant
Warfarin sodium
Zoocoumarin
Chemical FormulaC19H16O4
Average Molecular Mass308.328 g/mol
Monoisotopic Mass308.105 g/mol
CAS Registry Number81-81-2
IUPAC Name4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H-chromen-2-one
Traditional Namewarfarin
SMILESCC(=O)CC(C1=CC=CC=C1)C1=C(O)C2=CC=CC=C2OC1=O
InChI IdentifierInChI=1/C19H16O4/c1-12(20)11-15(13-7-3-2-4-8-13)17-18(21)14-9-5-6-10-16(14)23-19(17)22/h2-10,15,21H,11H2,1H3
InChI KeyInChIKey=PJVWKTKQMONHTI-UHFFFAOYNA-N
Chemical Taxonomy
Description 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.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassCoumarins and derivatives
Sub ClassHydroxycoumarins
Direct Parent4-hydroxycoumarins
Alternative Parents
Substituents
  • 4-hydroxycoumarin
  • Benzopyran
  • 1-benzopyran
  • Pyranone
  • Monocyclic benzene moiety
  • Benzenoid
  • Pyran
  • Heteroaromatic compound
  • Vinylogous acid
  • Ketone
  • Lactone
  • Oxacycle
  • Organoheterocyclic compound
  • Organic oxygen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxide
  • Organooxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceSolid (MSDS, A308).
Experimental Properties
PropertyValue
Melting Point161°C
Boiling PointNot Available
Solubility17 mg/L (at 20°C)
LogP2.7
Predicted Properties
PropertyValueSource
Water Solubility0.047 g/LALOGPS
logP2.41ALOGPS
logP2.74ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)5.56ChemAxon
pKa (Strongest Basic)-6.9ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area63.6 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity86.86 m³·mol⁻¹ChemAxon
Polarizability31.9 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-014i-0293000000-848341bcbd6a3f0a2c6bView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-014i-0293000000-848341bcbd6a3f0a2c6bView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0udl-3190000000-b963cb54bb6abedefbe3View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00xr-7195000000-ca3a892fd51e0eac1242View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-0429000000-1e818b579dc7a0fade2dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0900000000-f568338c06cd9b4762acView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0900000000-acdd0ed19e403aa73c77View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0bt9-0539000000-5b1c7c6c812ba72325e3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-0009000000-e461e1aca7977a2838adView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0w29-0960000000-9fa099190280529cd891View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00di-0910000000-d7dbaf6e7b34ee85e1f7View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-03di-0920000000-4fb886a5c160afa86df9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-03di-0920000000-ad608fe7680a2adf9d90View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0ik9-0942000000-5864f2d15892753d6a8bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4l-0197000000-a98e039dbdc8da6c3b7cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-052f-0292000000-d9a969b41fe312282de6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00di-2690000000-f20b105406ab790d37f0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-1149000000-4072cf2742b0e6164f82View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0bt9-5988000000-eb075587f79ddb4af966View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-052f-9350000000-47075e4967528dede6f3View in MoNA
MSMass Spectrum (Electron Ionization)splash10-014i-7692000000-6e3993fee62d7eb7438eView in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureOral ; Inhalation ; Dermal Rapidly absorbed following oral administration with considerable interindividual variations. Also absorbed percutaneously.
Mechanism of ToxicityWarfarin 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 proteins, 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. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.
MetabolismMetabolized stereo- and regio-selectively by hepatic microsomal enzymes. S-warfarin is predominantly metabolized by cytochrome P450 (CYP) 2C9 to yield the 6- and 7-hydroxylated metabolites. R-warfarin is metabolized by CYP1A1, 1A2, and 3A4 to yield 6-, 8-, and 10-hydroxylated metabolites. Hydroxylated metabolites may be further conjugated prior to excretion into bile and urine. UGT1A1 appears to be responsible for producing the 6-O-glucuronide of warfarin, with a possibly contribution from UGT1A10. Five UGT1As may be involved in the formation of 7-O-glucuronide warfarin. S-warfarin has higher potency than R-warfarin and genetic polymorphisms in CYP2C9 may dramatically decrease clearance of and increase toxicity of the medication. In man, the dextrowarfarin enantiomorph is metabolized by side chain reduction to a secondary alcohol, whereas levowarfarin is metabolized by oxidation of the ring, primarily to 7-hydroxywarfarin. These inactive metabolic products are to some extent conjugated with glucuronic acid, undergo an enterohepatic circulation, & are ultimately excreted in urine & stool. (7) Route of Elimination: The elimination of warfarin is almost entirely by metabolism. Very little warfarin is excreted unchanged in urine. The metabolites are principally excreted into the urine; and to a lesser extent into the bile. Half Life: R-warfarin t1/2=37-89 hours; S-warfarin t1/2=21-43 hours.
Toxicity ValuesLD50: 374 mg/kg (Oral, Mouse) (1)
Lethal DoseThe lowest reported lethal dose in humans is 6667 ug/kg. (8)
Carcinogenicity (IARC Classification)No indication of carcinogenicity (not listed by IARC). (19)
Uses/SourcesWarfarin is an anticoagulant drug and rodenticide derived from coumarin. As a drug it is used for the treatment of retinal vascular occlusion, pulmonary embolism, cardiomyopathy, atrial fibrillation and flutter, cerebral embolism, transient cerebral ischaemia, arterial embolism and thrombosis. (1)
Minimum Risk LevelNot Available
Health EffectsHemorrhage is the most prevalent adverse effect of oral anticoagulant therapy. The incidence of bleeding complications is related to the duration and range of therapy. (20)
SymptomsLD50=374 (orally in mice)
TreatmentThe primary antidote to warfarin poisoning is immediate administration of vitamin K1 (initially slow intravenous injections of 10-25 mg repeated all 3-6 hours until normalisation of the prothrombin time; then 10 mg orally four times daily as a "maintenance dose"). It is an extremely effective antidote, provided the poisoning is caught before too much damage has been done to the victim's circulatory system. At high doses warfarin can affect the body for many months, and the antidote must be administered regularly for a long period of time. (23)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00682
HMDB IDHMDB01935
PubChem Compound ID54678486
ChEMBL IDCHEMBL1464
ChemSpider ID10442445
KEGG IDC01541
UniProt IDNot Available
OMIM ID
ChEBI ID10033
BioCyc IDNot Available
CTD IDD014859
Stitch IDWarfarin
PDB IDNot Available
ACToR ID3232
Wikipedia LinkWarfarin
References
Synthesis Reference

Nasri W. Badran, “Microcrystalline 3-(alpha-acetonylbenzyl)-4-hydroxycoumarin (warfarin) and methods of making.” U.S. Patent US4113744, issued April, 1960.

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E: The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):204S-233S. [15383473 ]
  3. Whitlon DS, Sadowski JA, Suttie JW: Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. Biochemistry. 1978 Apr 18;17(8):1371-7. [646989 ]
  4. Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW: Identification of the gene for vitamin K epoxide reductase. Nature. 2004 Feb 5;427(6974):541-4. [14765195 ]
  5. Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hortnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, Muller CR, Strom TM, Oldenburg J: Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004 Feb 5;427(6974):537-41. [14765194 ]
  6. Hirsh J, Fuster V, Ansell J, Halperin JL: American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol. 2003 May 7;41(9):1633-52. [12742309 ]
  7. Yamamoto N, Naraparaju VR: Role of vitamin D3-binding protein in activation of mouse macrophages. J Immunol. 1996 Aug 15;157(4):1744-9. [8759764 ]
  8. Kilpatrick IC, Traut M, Heal DJ: Monoamine oxidase inhibition is unlikely to be relevant to the risks associated with phentermine and fenfluramine: a comparison with their abilities to evoke monoamine release. Int J Obes Relat Metab Disord. 2001 Oct;25(10):1454-8. [11673765 ]
  9. Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M, Wells PS: Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005 May 23;165(10):1095-106. [15911722 ]
  10. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G: Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):160S-198S. doi: 10.1378/chest.08-0670. [18574265 ]
  11. Freedman MD: Oral anticoagulants: pharmacodynamics, clinical indications and adverse effects. J Clin Pharmacol. 1992 Mar;32(3):196-209. [1564123 ]
  12. Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
  13. Gilman AG, Goodman LS, and Gilman A (eds) (1980). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York, NY: Macmillan Publishing Co., Inc.
  14. Sax NI, Lewis RJ (1989). Dangerous properties of industrial materials. 7th edition. New York, NY: Van Nostrand Reinhold Company.
  15. Macina, Orest T.; Schardein, James L. (2007). “Warfarin”. Human Developmental Toxicants. Boca Raton: CRC Taylor & Francis. pp. 193–4
  16. Loftus, Christopher M. (1995). “Fetal toxicity of common neurosurgical drugs”. Neurosurgical Aspects of Pregnancy. Park Ridge, Ill: American Association of Neurological Surgeons. pp. 11–3.
  17. Loftus, Christopher M. (1995). Fetal toxicity of common neurosurgical drugs. Neurosurgical Aspects of Pregnancy. Park Ridge, Ill: American Association of Neurological Surgeons. pp. 11-3.
  18. Macina, Orest T.; Schardein, James L. (2007). Warfarin. Human Developmental Toxicants. Boca Raton: CRC Taylor & Francis. pp. 193-4
  19. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  20. Wikipedia. Dinitrotoluene. Last Updated 10 June 2009. [Link]
  21. Hacco (2008). Material Safety Data Sheet for Warfarin Concentrate. [Link]
  22. Wikipedia. Coumarin. Last Updated 21 July 2009. [Link]
  23. Wikipedia. Brodifacoum. Last Updated 22 June 2009. [Link]
  24. Drugs.com [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

General Function:
Vitamin-k-epoxide reductase (warfarin-sensitive) activity
Specific 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.
Gene Name:
VKORC1
Uniprot ID:
Q9BQB6
Molecular Weight:
18234.3 Da
References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Zhu Y, Shennan M, Reynolds KK, Johnson NA, Herrnberger MR, Valdes R Jr, Linder MW: Estimation of warfarin maintenance dose based on VKORC1 (-1639 G>A) and CYP2C9 genotypes. Clin Chem. 2007 Jul;53(7):1199-205. Epub 2007 May 17. [17510308 ]
  3. Yin T, Miyata T: Warfarin dose and the pharmacogenomics of CYP2C9 and VKORC1 - rationale and perspectives. Thromb Res. 2007;120(1):1-10. Epub 2006 Dec 11. [17161452 ]
  4. Fukuda T, Tanabe T, Ohno M, Tougou K, Fujio Y, Azuma J, Yamamoto I, Takeda A: Warfarin dose requirement for patients with both VKORC1 3673A/A and CYP2C9*3/*3 genotypes. Clin Pharmacol Ther. 2006 Nov;80(5):553-4. [17112813 ]
  5. Osman A, Enstrom C, Lindahl TL: Plasma S/R ratio of warfarin co-varies with VKORC1 haplotype. Blood Coagul Fibrinolysis. 2007 Apr;18(3):293-6. [17413769 ]
  6. Limdi NA, McGwin G, Goldstein JA, Beasley TM, Arnett DK, Adler BK, Baird MF, Acton RT: Influence of CYP2C9 and VKORC1 1173C/T genotype on the risk of hemorrhagic complications in African-American and European-American patients on warfarin. Clin Pharmacol Ther. 2008 Feb;83(2):312-21. Epub 2007 Jul 25. [17653141 ]
General Function:
Toxic substance binding
Specific Function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation2 uMNot AvailableBindingDB 50343352
Dissociation4.677 uMNot AvailableBindingDB 50343352
Dissociation5.4 uMNot AvailableBindingDB 50343352
Dissociation12 uMNot AvailableBindingDB 50343352
Dissociation510 uMNot AvailableBindingDB 50343352
References
  1. Giannetti AM, Wong H, Dijkgraaf GJ, Dueber EC, Ortwine DF, Bravo BJ, Gould SE, Plise EG, Lum BL, Malhi V, Graham RA: Identification, characterization, and implications of species-dependent plasma protein binding for the oral Hedgehog pathway inhibitor vismodegib (GDC-0449). J Med Chem. 2011 Apr 28;54(8):2592-601. doi: 10.1021/jm1008924. Epub 2011 Mar 25. [21438527 ]
  2. Lazaro E, Lowe PJ, Briand X, Faller B: New approach to measure protein binding based on a parallel artificial membrane assay and human serum albumin. J Med Chem. 2008 Apr 10;51(7):2009-17. doi: 10.1021/jm7012826. Epub 2008 Mar 19. [18348514 ]
General Function:
Vitamin-k-epoxide reductase (warfarin-sensitive) activity
Specific Function:
Involved in vitamin K metabolism. Can reduce inactive vitamin K 2,3-epoxide to active vitamin K (in vitro), and may contribute to vitamin K-mediated protection against oxidative stress. Plays a role in vitamin K-dependent gamma-carboxylation of Glu residues in target proteins.
Gene Name:
VKORC1L1
Uniprot ID:
Q8N0U8
Molecular Weight:
19835.425 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General Function:
Not Available
Specific Function:
Functions as 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.
Gene Name:
ORM1
Uniprot ID:
P02763
Molecular Weight:
23511.38 Da
References
  1. Herve F, Duche JC, d'Athis P, Marche C, Barre J, Tillement JP: Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Pharmacogenetics. 1996 Oct;6(5):403-15. [8946472 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory20 uMNot AvailableBindingDB 50343352
References
  1. Afzelius L, Zamora I, Masimirembwa CM, Karlen A, Andersson TB, Mecucci S, Baroni M, Cruciani G: Conformer- and alignment-independent model for predicting structurally diverse competitive CYP2C9 inhibitors. J Med Chem. 2004 Feb 12;47(4):907-14. [14761192 ]
General Function:
Not Available
Specific Function:
Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis.
Gene Name:
FBF1
Uniprot ID:
Q8TES7
Molecular Weight:
125445.19 Da
References
  1. Krishnakumar SS, Panda D: Spatial relationship between the prodan site, Trp-214, and Cys-34 residues in human serum albumin and loss of structure through incremental unfolding. Biochemistry. 2002 Jun 11;41(23):7443-52. [12044178 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
References
  1. Rulcova A, Prokopova I, Krausova L, Bitman M, Vrzal R, Dvorak Z, Blahos J, Pavek P: Stereoselective interactions of warfarin enantiomers with the pregnane X nuclear receptor in gene regulation of major drug-metabolizing cytochrome P450 enzymes. J Thromb Haemost. 2010 Dec;8(12):2708-17. doi: 10.1111/j.1538-7836.2010.04036.x. [20735727 ]
General Function:
Serine-type endopeptidase activity
Specific Function:
Likely to represent a ubiquitous endoprotease activity within constitutive secretory pathways and capable of cleavage at the RXXX[KR]R consensus motif.
Gene Name:
PCSK7
Uniprot ID:
Q16549
Molecular Weight:
86246.44 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5024.59 uMNot AvailableBindingDB 50343352
References
  1. de Oliveira CM, Silva GH, Regasini LO, Flausino O, Lopez SN, Abissi BM, Berlinck RG, Sette LD, Bonugli-Santos RC, Rodrigues A, Bolzani Vda S, Araujo AR: Xylarenones C-E from an endophytic fungus isolated from Alibertia macrophylla. J Nat Prod. 2011 Jun 24;74(6):1353-7. doi: 10.1021/np1005983. Epub 2011 Apr 21. [21510613 ]
General Function:
Thrombospondin receptor activity
Specific Function:
Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.
Gene Name:
F2
Uniprot ID:
P00734
Molecular Weight:
70036.295 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
Gene Name:
PPARG
Uniprot ID:
P37231
Molecular Weight:
57619.58 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.79 uMTox21_PPARg_BLA_Agonist_ratioTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]