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Version 2.5
Creation Date 2007-07-24 08:32:02
Update Date 2009-06-23 18:07:49
Primary Accession Number DB01418
Secondary Accession Number Not Available
Name Acenocoumarol
Drug Type
  • Approved
  • Small Molecule
Description A coumarin that is used as an anticoagulant. Its actions and uses are similar to those of warfarin. (From Martindale, The Extra Pharmacopoeia, 30th ed, p233)
Synonyms
  1. Acenocoumarin
  2. Acenocoumarolum [inn-latin]
  3. Nicoumalone
  4. Nicumalon
  5. Nitrophenylacetylethyl-4-hydroxycoumarine
  6. Nitrovarfarian
  7. Nitrowarfarin
Brand Names
  1. Ascumar
  2. Neositron
  3. Sincoumar
  4. Sinkumar
  5. Sinthrom
  6. Sinthrome
  7. Sintrom
  8. Syncoumar
  9. Syncumar
  10. Syntrom
  11. Zotil
Brand Mixtures Not Available
Chemical IUPAC Name 2-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]chromen-4-one
Chemical Formula C19H15NO6
Chemical Structure Structure
CAS Registry Number 152-72-7
InChI Identifier InChI=1/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/h2-9,15,23H,10H2,1H3
InChI Key WWBYDEQHYAEHLT-UHFFFAOYAP
KEGG Drug Not Available
KEGG Compound Not Available
PubChem Compound 9052 Link Image
PubChem Substance 10321722 Link Image
ChEBI ID Not Available
PharmGKB ID PA452632 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 00010383 Link Image
RxList Link Not Available
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Acenocoumarol Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 353.3255
Monoisotopic Molecular Weight 353.0899
State Solid
Melting Point 197 oC
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 1.05e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 1.98 [SANGSTER (1994)] Source: PhysProp
Predicted LogP 2.55 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.53 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CC(=O)C[C@@H](C1=CC=C(C=C1)[N+]([O-])=O)C1=C(O)OC2=CC=CC=C2C1=O
Canonical SMILES CC(=O)CC(C1=CC=C(C=C1)[N+]([O-])=O)C1=C(O)OC2=CC=CC=C2C1=O
Drug Category
  • Anticoagulants
  • Coumarin and Indandione Derivatives
ATC Codes
AHFS Codes
  • 20:12.04.08
Indication For the treatment and prevention of thromboembolic diseases.
Pharmacology Acenocoumarol is a coumarin that is used as an anticoagulant. Its actions and uses are similar to those of warfarin. (From Martindale, The Extra Pharmacopoeia, 30th ed, p233)
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 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 decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.
Absorption Not Available
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 poisoning 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.
Protein Binding Not Available
Biotransformation Hepatic.
Half Life 8 to 11 hours.
Dosage Forms
Form Route
Tablet Oral
Tablet Oral
Patient Information Not Available
Contraindications Not Available
Interactions Not Available
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. 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. [PubMed Link Image]
  2. Lengyel M: [Warfarin or acenocoumarol is better in the anticoagulant treatment of chronic atrial fibrillation?] Orv Hetil. 2004 Dec 26;145(52):2619-21. [PubMed Link Image]
  3. Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [PubMed Link Image]
  4. 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. [PubMed Link Image]
  5. Wikipedia Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 1A2 (CYP1A2)
  2. Cytochrome P450 2C9 (CYP2C9)
Targets
  1. Serum albumin
  2. Vitamin K epoxide reductase complex subunit 1
  3. Alpha-1-acid glycoprotein 1
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 1A2 (CYP1A2)
Enzyme 1 Gene Name CYP1A2
Enzyme 1 SwissProt ID P05177 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >P05177|CP1A2_HUMAN Cytochrome P450 1A2 - Homo sapiens (Human). 
MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPLLGHVLTLGKN
PHLALSRMSQRYGDVLQIRIGSTPVLVLSRLDTIRQALVRQGDDFKGRPDLYTSTLITDG
QSLTFSTDSGPVWAARRRLAQNALNTFSIASDPASSSSCYLEEHVSKEAKALISRLQELM
AGPGHFDPYNQVVVSVANVIGAMCFGQHFPESSDEMLSLVKNTHEFVETASSGNPLDFFP
ILRYLPNPALQRFKAFNQRFLWFLQKTVQEHYQDFDKNSVRDITGALFKHSKKGPRASGN
LIPQEKIVNLVNDIFGAGFDTVTTAISWSLMYLVTKPEIQRKIQKELDTVIGRERRPRLS
DRPQLPYLEAFILETFRHSSFLPFTIPHSTTRDTTLNGFYIPKKCCVFVNQWQVNHDPEL
WEDPSEFRPERFLTADGTAINKPLSEKMMLFGMGKRRCIGEVLAKWEIFLFLAILLQQLE
FSVPPGVKVDLTPIYGLTMKHARCEHVQARRFSIN
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Cytochrome P450 2C9 (CYP2C9)
Enzyme 2 Gene Name CYP2C9
Enzyme 2 SwissProt ID P11712 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >sp|P11712|CP2C9_HUMAN Cytochrome P450 2C9 (EC 1.14.13.80) 
MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKV
YGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFM
KSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYID
LLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK
KSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP
PFYQLCFIPV
Drug Target 1 [top]
Target 1 ID 587
Target 1 Name Serum albumin
Target 1 Synonyms
  1. Serum albumin precursor
Target 1 Gene Name ALB
Target 1 Protein Sequence >Serum albumin precursor 
MKWVTFISLLFLFSSAYSRGVFRRDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPF
EDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEP
ERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLF
FAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAV
ARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLK
ECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYAR
RHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFE
QLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVV
LNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTL
SEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLV
AASQAALGL
Target 1 Number of Residues 619
Target 1 Molecular Weight 69367
Target 1 Theoretical pI 6.21
Target 1 GO Classification
Function
transporter activity
carrier activity
Process
physiological process
cellular physiological process
transport
Component
extracellular region
extracellular space
Target 1 General Function Involved in antioxidant activity
Target 1 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
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • 1-18
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 28590 Link Image
Target 1 UniProtKB/Swiss-Prot ID P02768 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name ALBU_HUMAN Link Image
Target 1 PDB ID 1HA2 Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Secreted protein
Target 1 Gene Sequence >1830 bp 
ATGAAGTGGGTAACCTTTATTTCCCTTCTTTTTCTCTTTAGCTCGGCTTATTCCAGGGGT
GTGTTTCGTCGAGATGCACACAAGAGTGAGGTTGCTCATCGGTTTAAAGATTTGGGAGAA
GAAAATTTCAAAGCCTTGGTGTTGATTGCCTTTGCTCAGTATCTTCAGCAGTGTCCATTT
GAAGATCATGTAAAATTAGTGAATGAAGTAACTGAATTTGCAAAAACATGTGTTGCTGAT
GAGTCAGCTGAAAATTGTGACAAATCACTTCATACCCTTTTTGGAGACAAATTATGCACA
GTTGCAACTCTTCGTGAAACCTATGGTGAAATGGCTGACTGCTGTGCAAAACAAGAACCT
GGGAGAAATGAATGCTTCTTGCAACACAAAGATGACAACCCAAACCTCCCCCGATTGGTG
AGACCAGAGGTTGATGTGATGTGCACTGCTTTTCATGACAATGAAGAGACATTTTTGAAA
AAATACTTATATGAAATTGCCAGAAGACATCCTTACTTTTATGCCCCGGAACTCCTTTTC
TTTGCTAAAAGGTATAAAGCTGCTTTTACAGAATGTTGCCAAGCTGCTGATAAAGCTGCC
TGCCTGTTGCCAAAGCTCGATGAACTTCGGGATGAAGGGAAGGCTTCGTCTGCCAAACAG
AGACTCAAGTGTGCCAGTCTCCAAAAATTTGGAGAAAGAGCTTTCAAAGCATGGGCAGTA
GCTCGCCTGAGCCAGAGATTTCCCAAAGCTGAGTTTGCAGAAGTTTCCAAGTTAGTGACA
GATCTTACCAAAGTCCACACGGAATGCTGCCATGGAGATCTGCTTGAATGTGCTGATGAC
AGGGCGGACCTTGCCAAGTATATCTGTGAAAATCAAGATTCGATCTCCAGTAAACTGAAG
GAATGCTGTGAAAAACCTCTGTTGGAAAAATCCCACTGCATTGCCGAAGTGGAAAATGAT
GAGATGCCTGCTGACTTGCCTTCATTAGCTGCTGATTTTGTTGAAAGTAAGGATGTTTGC
AAAAACTATGCTGAGGCAAAGGATGTCTTCTTGGGCATGTTTTTGTATGAATATGCAAGA
AGGCATCCTGATTACTCTGTCGTGCTGCTGCTGAGACTTGCCAAGACATATGAAACCACT
CTAGAGAAGTGCTGTGCCGCTGCAGATCCTCATGAATGCTATGCCAAAGTGTTCGATGAA
TTTAAACCTCTTGTGGAAGAGCCTCAGAATTTAATCAAACAAAATTGTGAGCTTTTTGAG
CAGCTTGGAGAGTACAAATTCCAGAATGCGCTGTTAGTTCGTTACACCAAGAAAGTACCC
GAAGTGTCAACTCCAACTCTTGTAGAGGTCTCAAGAAACCTAGGAAAAGTGGGCAGCAAA
TGTTGTAAACATCCTGAAGCAAAAAGAATGCCCTGTGCAGAAGACTATCTATCCGTGGTC
CTGAACCAGTTATGTGTGTTGCATGAGAAAACGCCAGTAAGTGACAGAGTCACCAAATGC
TGCACAGAATCCTTGGTGAACAGGCGACCATGCTTTTCAGCTCTGGAAGTCGATGAAACA
TACGTTCCCAAAGAGTTTAATGCTGAAACATTCACCTTCCATGCAGATATATGCACACTT
TCTGAGAAGGAGAGACAAATCAAGAAACAAACTGCACTTGTTGAGCTCGTGAAACACAAG
CCCAAGGCAACAAAAGAGCAACTGAAAGCTGTTATGGATGATTTCGCTGCTTTTGTAGAG
AAGTGCTGCAAGGCTGACGATAAGGAGACCTGCTTTGCCGAGGAGGGTAAAAAACTTGTT
GCTGCAAGTCAAGCTGCCTTAGGCTTATAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID ALB Link Image
Target 1 GenAtlas ID ALB Link Image
Target 1 HGNC ID HGNC:399 Link Image
Target 1 Chromosome Location 4
Target 1 Locus 4q11-q13
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Sugio S, Kashima A, Mochizuki S, Noda M, Kobayashi K: Crystal structure of human serum albumin at 2.5 A resolution. Protein Eng. 1999 Jun;12(6):439-46. [PubMed Link Image]
  2. Bhattacharya AA, Curry S, Franks NP: Binding of the general anesthetics propofol and halothane to human serum albumin. High resolution crystal structures. J Biol Chem. 2000 Dec 8;275(49):38731-8. [PubMed Link Image]
  3. Minchiotti L, Campagnoli M, Rossi A, Cosulich ME, Monti M, Pucci P, Kragh-Hansen U, Granel B, Disdier P, Weiller PJ, Galliano M: A nucleotide insertion and frameshift cause albumin Kenitra, an extended and O-glycosylated mutant of human serum albumin with two additional disulfide bridges. Eur J Biochem. 2001 Jan;268(2):344-52. [PubMed Link Image]
  4. Yu Y, Zhang C, Zhou G, Wu S, Qu X, Wei H, Xing G, Dong C, Zhai Y, Wan J, Ouyang S, Li L, Zhang S, Zhou K, Zhang Y, Wu C, He F: Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs. Genome Res. 2001 Aug;11(8):1392-403. [PubMed Link Image]
  5. Spahr CS, Davis MT, McGinley MD, Robinson JH, Bures EJ, Beierle J, Mort J, Courchesne PL, Chen K, Wahl RC, Yu W, Luethy R, Patterson SD: Towards defining the urinary proteome using liquid chromatography-tandem mass spectrometry. I. Profiling an unfractionated tryptic digest. Proteomics. 2001 Jan;1(1):93-107. [PubMed Link Image]
  6. Petitpas I, Grune T, Bhattacharya AA, Curry S: Crystal structures of human serum albumin complexed with monounsaturated and polyunsaturated fatty acids. J Mol Biol. 2001 Dec 14;314(5):955-60. [PubMed Link Image]
  7. Meloun B, Moravek L, Kostka V: Complete amino acid sequence of human serum albumin. FEBS Lett. 1975 Oct 15;58(1):134-7. [PubMed Link Image]
  8. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [PubMed Link Image]
  9. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [PubMed Link Image]
  10. Minchiotti L, Galliano M, Stoppini M, Ferri G, Crespeau H, Rochu D, Porta F: Two alloalbumins with identical electrophoretic mobility are produced by differently charged amino acid substitutions. Biochim Biophys Acta. 1992 Mar 12;1119(3):232-8. [PubMed Link Image]
  11. 1518850 Carlson J, Sakamoto Y, Laurell CB, Madison J, Watkins S, Putnam FW: Alloalbuminemia in Sweden: structural study and phenotypic distribution of nine albumin variants. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8225-9.
  12. 1630489 He XM, Carter DC: Atomic structure and chemistry of human serum albumin. Nature. 1992 Jul 16;358(6383):209-15.
  13. 1859851 Peach RJ, Brennan SO: Structural characterization of a glycoprotein variant of human serum albumin: albumin Casebrook (494 Asp----Asn). Biochim Biophys Acta. 1991 Jul 26;1097(1):49-54.
  14. 1946412 Madison J, Arai K, Sakamoto Y, Feld RD, Kyle RA, Watkins S, Davis E, Matsuda Y, Amaki I, Putnam FW: Genetic variants of serum albumin in Americans and Japanese. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9853-7.
  15. 2068071 Watkins S, Madison J, Davis E, Sakamoto Y, Galliano M, Minchiotti L, Putnam FW: A donor splice mutation and a single-base deletion produce two carboxyl-terminal variants of human serum albumin. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):5959-63.
  16. 2104980 Brennan SO, Myles T, Peach RJ, Donaldson D, George PM: Albumin Redhill (-1 Arg, 320 Ala----Thr): a glycoprotein variant of human serum albumin whose precursor has an aberrant signal peptidase cleavage site. Proc Natl Acad Sci U S A. 1990 Jan;87(1):26-30.
  17. 2247440 Galliano M, Minchiotti L, Porta F, Rossi A, Ferri G, Madison J, Watkins S, Putnam FW: Mutations in genetic variants of human serum albumin found in Italy. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8721-5.
  18. 2374930 Carter DC, He XM: Structure of human serum albumin. Science. 1990 Jul 20;249(4966):302-3.
  19. 2404284 Arai K, Madison J, Shimizu A, Putnam FW: Point substitutions in albumin genetic variants from Asia. Proc Natl Acad Sci U S A. 1990 Jan;87(1):497-501.
  20. 2419329 Urano Y, Watanabe K, Sakai M, Tamaoki T: The human albumin gene. Characterization of the 5' and 3' flanking regions and the polymorphic gene transcripts. J Biol Chem. 1986 Mar 5;261(7):3244-51.
  21. 2437111 Carraway RE, Mitra SP, Cochrane DE: Structure of a biologically active neurotensin-related peptide obtained from pepsin-treated albumin(s). J Biol Chem. 1987 May 5;262(13):5968-73.
  22. 2727704 Carter DC, He XM, Munson SH, Twigg PD, Gernert KM, Broom MB, Miller TY: Three-dimensional structure of human serum albumin. Science. 1989 Jun 9;244(4909):1195-8.
  23. 2762316 Arai K, Madison J, Huss K, Ishioka N, Satoh C, Fujita M, Neel JV, Sakurabayashi I, Putnam FW: Point substitutions in Japanese alloalbumins. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6092-6.
  24. 2911589 Arai K, Ishioka N, Huss K, Madison J, Putnam FW: Identical structural changes in inherited albumin variants from different populations. Proc Natl Acad Sci U S A. 1989 Jan;86(2):434-8.
  25. 3009475 Minghetti PP, Ruffner DE, Kuang WJ, Dennison OE, Hawkins JW, Beattie WG, Dugaiczyk A: Molecular structure of the human albumin gene is revealed by nucleotide sequence within q11-22 of chromosome 4. J Biol Chem. 1986 May 25;261(15):6747-57.
  26. 3087352 Mogard MH, Kobayashi R, Chen CF, Lee TD, Reeve JR Jr, Shively JE, Walsh JH: The amino acid sequence of kinetensin, a novel peptide isolated from pepsin-treated human plasma: homology with human serum albumin, neurotensin and angiotensin. Biochem Biophys Res Commun. 1986 May 14;136(3):983-8.
  27. 3474609 Takahashi N, Takahashi Y, Blumberg BS, Putnam FW: Amino acid substitutions in genetic variants of human serum albumin and in sequences inferred from molecular cloning. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4413-7.
  28. 3479777 Takahashi N, Takahashi Y, Isobe T, Putnam FW, Fujita M, Satoh C, Neel JV: Amino acid substitutions in inherited albumin variants from Amerindian and Japanese populations. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8001-5.
  29. 3828358 Brennan SO, Herbert P: Albumin Canterbury (313 Lys----Asn). A point mutation in the second domain of serum albumin. Biochim Biophys Acta. 1987 Apr 8;912(2):191-7.
  30. 6171778 Lawn RM, Adelman J, Bock SC, Franke AE, Houck CM, Najarian RC, Seeburg PH, Wion KL: The sequence of human serum albumin cDNA and its expression in E. coli. Nucleic Acids Res. 1981 Nov 25;9(22):6103-114.
  31. 6275391 Dugaiczyk A, Law SW, Dennison OE: Nucleotide sequence and the encoded amino acids of human serum albumin mRNA. Proc Natl Acad Sci U S A. 1982 Jan;79(1):71-5.
  32. 656055 Jacobsen C: Lysine residue 240 of human serum albumin is involved in high-affinity binding of bilirubin. Biochem J. 1978 May 1;171(2):453-9.
  33. 7852505 Rushbrook JI, Becker E, Schussler GC, Divino CM: Identification of a human serum albumin species associated with familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab. 1995 Feb;80(2):461-7.
  34. 7895732 Corbett JM, Wheeler CH, Baker CS, Yacoub MH, Dunn MJ: The human myocardial two-dimensional gel protein database: update 1994. Electrophoresis. 1994 Nov;15(11):1459-65.
  35. 7902134 Galliano M, Minchiotti L, Iadarola P, Stoppini M, Giagnoni P, Watkins S, Madison J, Putnam FW: Protein and DNA sequence analysis of a 'private' genetic variant: albumin Ortonovo (Glu-505-->Lys). Biochim Biophys Acta. 1993 Nov 25;1225(1):27-32.
  36. 8022807 Madison J, Galliano M, Watkins S, Minchiotti L, Porta F, Rossi A, Putnam FW: Genetic variants of human serum albumin in Italy: point mutants and a carboxyl-terminal variant. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6476-80.
  37. 8048949 Sunthornthepvarakul T, Angkeow P, Weiss RE, Hayashi Y, Refetoff S: An identical missense mutation in the albumin gene results in familial dysalbuminemic hyperthyroxinemia in 8 unrelated families. Biochem Biophys Res Commun. 1994 Jul 29;202(2):781-7.
  38. 8347685 Brennan SO, Fellowes AP: Albumin Hawkes Bay; a low level variant caused by loss of a sulphydryl group at position 177. Biochim Biophys Acta. 1993 Aug 4;1182(1):46-50.
  39. 8513793 Minchiotti L, Galliano M, Zapponi MC, Tenni R: The structural characterization and bilirubin-binding properties of albumin Herborn, a [Lys240-->Glu] albumin mutant. Eur J Biochem. 1993 Jun 1;214(2):437-44.
  40. 9329347 Wada N, Chiba H, Shimizu C, Kijima H, Kubo M, Koike T: A novel missense mutation in codon 218 of the albumin gene in a distinct phenotype of familial dysalbuminemic hyperthyroxinemia in a Japanese kindred. J Clin Endocrinol Metab. 1997 Oct;82(10):3246-50.
  41. 955075 Walker JE: Lysine residue 199 of human serum albumin is modified by acetylsalicyclic acid. FEBS Lett. 1976 Jul 15;66(2):173-5.
  42. 9589637 Sunthornthepvarakul T, Likitmaskul S, Ngowngarmratana S, Angsusingha K, Kitvitayasak S, Scherberg NH, Refetoff S: Familial dysalbuminemic hypertriiodothyroninemia: a new, dominantly inherited albumin defect. J Clin Endocrinol Metab. 1998 May;83(5):1448-54.
  43. 9731778 Curry S, Mandelkow H, Brick P, Franks N: Crystal structure of human serum albumin complexed with fatty acid reveals an asymmetric distribution of binding sites. Nat Struct Biol. 1998 Sep;5(9):827-35.
Target 1 Drug References
  1. 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. [PubMed Link Image]
  2. 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. [PubMed Link Image]
  3. 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. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 787
Target 2 Name Vitamin K epoxide reductase complex subunit 1
Target 2 Synonyms
  1. EC 1.1.4.1
  2. Vitamin K1 2,3-epoxide reductase subunit 1
Target 2 Gene Name VKORC1
Target 2 Protein Sequence >Vitamin K epoxide reductase complex subunit 1 
MGSTWGSPGWVRLALCLTGLVLSLYALHVKAARARDRDYRALCDVGTAISCSRVFSSRWG
RGFGLVEHVLGQDSILNQSNSIFGCIFYTLQLLLGCLRTRWASVLMLLSSLVSLAGSVYL
AWILFFVLYDFCIVCITTYAINVSLMWLSFRKVQEPQGKAKRH
Target 2 Number of Residues 165
Target 2 Molecular Weight 18235
Target 2 Theoretical pI 9.58
Target 2 GO Classification Not Available
Target 2 General Function Involved in vitamin-K-epoxide reductase (warfarin-sensitive) activity
Target 2 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
Target 2 Pathways
Name SMPDB Link KEGG Link
Biosynthesis of steroids map00100 Link Image
Target 2 Reactions
  • 2-methyl-3-phytyl-1,4-naphthoquinone + oxidized dithiothreitol = 2,3-epoxy-2,3-dihydro-2-methyl-3-phytyl-1,4-naphthoquinone + 1,4-dithiothreitol
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 9-29
  • 101-123
  • 127-149
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 40217983 Link Image
Target 2 UniProtKB/Swiss-Prot ID Q9BQB6 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name VKOR1_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Endoplasmic reticulum
  • endoplasmic reticulum membrane
  • multi-pass membrane protein
Target 2 Gene Sequence >492 bp 
ATGGGCAGCACCTGGGGGAGCCCTGGCTGGGTGCGGCTCGCTCTTTGCCTGACGGGCTTA
GTGCTCTCGCTCTACGCGCTGCACGTGAAGGCGGCGCGCGCCCGGGACCGGGATTACCGC
GCGCTCTGCGACGTGGGCACCGCCATCAGCTGTTCGCGCGTCTTCTCCTCCAGGTGGGGC
AGGGGTTTCGGGCTGGTGGAGCATGTGCTGGGACAGGACAGCATCCTCAATCAATCCAAC
AGCATATTCGGTTGCATCTTCTACACACTACAGCTATTGTTAGGTTGCCTGCGGACACGC
TGGGCCTCTGTCCTGATGCTGCTGAGCTCCCTGGTGTCTCTCGCTGGTTCTGTCTACCTG
GCCTGGATCCTGTTCTTCGTGCTCTATGATTTCTGCATTGTTTGTATCACCACCTATGCT
ATCAACGTGAGCCTGATGTGGCTCAGTTTCCGGAAGGTCCAAGAACCCCAGGGCAAGGCT
AAGAGGCACTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID VKORC1 Link Image
Target 2 GenAtlas ID VKORC1 Link Image
Target 2 HGNC ID HGNC:23663 Link Image
Target 2 Chromosome Location 16
Target 2 Locus 16p11.2
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [PubMed Link Image]
Target 2 Drug References
  1. 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. [PubMed Link Image]
  2. 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. [PubMed Link Image]
  3. 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. [PubMed Link Image]
  4. 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. [PubMed Link Image]
  5. 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. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 1181
Target 3 Name Alpha-1-acid glycoprotein 1
Target 3 Synonyms
  1. AGP 1
  2. Alpha-1-acid glycoprotein 1 precursor
  3. OMD 1
  4. Orosomucoid-1
Target 3 Gene Name ORM1
Target 3 Protein Sequence >Alpha-1-acid glycoprotein 1 precursor 
MALSWVLTVLSLLPLLEAQIPLCANLVPVPITNATLDQITGKWFYIASAFRNEEYNKSVQ
EIQATFFYFTPNKTEDTIFLREYQTRQDQCIYNTTYLNVQRENGTISRYVGGQEHFAHLL
ILRDTKTYMLAFDVNDEKNWGLSVYADKPETTKEQLGEFYEALDCLRIPKSDVVYTDWKK
DKCEPLEKQHEKERKQEEGES
Target 3 Number of Residues 204
Target 3 Molecular Weight 23512
Target 3 Theoretical pI 4.66
Target 3 GO Classification
Function
transporter activity
binding
Process
physiological process
cellular physiological process
transport
Component
Not Available
Target 3 General Function Involved in immune modulation
Target 3 Specific Function Appears to function in modulating the activity of the immune system during the acute-phase reaction
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • 1-18
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 757907 Link Image
Target 3 UniProtKB/Swiss-Prot ID P02763 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name A1AG1_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Secreted protein
Target 3 Gene Sequence >606 bp 
ATGGCGCTGTCCTGGGTTCTTACAGTCCTGAGCCTCCTACCTCTGCTGGAAGCCCAGATC
CCATTGTGTGCCAACCTAGTACCGGTGCCCATCACCAACGCCACCCTGGACCAGATCACT
GGCAAGTGGTTTTATATCGCATCGGCCTTTCGAAACGAGGAGTACAATAAGTCGGTTCAG
GAGATCCAAGCAACCTTCTTTTACTTCACCCCCAACAAGACAGAGGACACGATCTTTCTC
AGAGAGTACCAGACCCGACAGGACCAGTGCATCTATAACACCACCTACCTGAATGTCCAG
CGGGAAAATGGGACCATCTCCAGATACGTGGGAGGCCAAGAGCATTTCGCTCACTTGCTG
ATCCTCAGGGACACCAAGACCTACATGCTTGCTTTTGACGTGAACGATGAGAAGAACTGG
GGGCTGTCTGTCTATGCTGACAAGCCAGAGACGACCAAGGAGCAACTGGGAGAGTTCTAC
GAAGCTCTCGACTGCTTGCGCATTCCCAAGTCAGATGTCGTGTACACCGATTGGAAAAAG
GATAAGTGTGAGCCACTGGAGAAGCAGCACGAGAAGGAGAGGAAACAGGAGGAGGGGGAA
TCCTAG
Target 3 GenBank Gene ID
Target 3 GeneCard ID ORM1 Link Image
Target 3 GenAtlas ID ORM1 Link Image
Target 3 HGNC ID HGNC:8498 Link Image
Target 3 Chromosome Location 9
Target 3 Locus 9q31-q32
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Zhang H, Li XJ, Martin DB, Aebersold R: Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechnol. 2003 Jun;21(6):660-6. Epub 2003 May 18. [PubMed Link Image]
  2. Treuheit MJ, Costello CE, Halsall HB: Analysis of the five glycosylation sites of human alpha 1-acid glycoprotein. Biochem J. 1992 Apr 1;283 ( Pt 1):105-12. [PubMed Link Image]
  3. Dente L, Ciliberto G, Cortese R: Structure of the human alpha 1-acid glycoprotein gene: sequence homology with other human acute phase protein genes. Nucleic Acids Res. 1985 Jun 11;13(11):3941-52. [PubMed Link Image]
  4. Dente L, Pizza MG, Metspalu A, Cortese R: Structure and expression of the genes coding for human alpha 1-acid glycoprotein. EMBO J. 1987 Aug;6(8):2289-96. [PubMed Link Image]
  5. Board PG, Jones IM, Bentley AK: Molecular cloning and nucleotide sequence of human alpha 1 acid glycoprotein cDNA. Gene. 1986;44(1):127-31. [PubMed Link Image]
  6. Ikenaka T, Ishiguro M, Emura J, Kaufmann H, Isemura S, Bauer W, Schmid K: Isolation and partial characterization of the cyanogen bromide fragments of 1 -acid glycoprotein and the elucidation of the amino acid sequence of the carboxyl-terminal cyanogen bromide fragment. Biochemistry. 1972 Sep 26;11(20):3817-29. [PubMed Link Image]
  7. Schmid K, Burgi W, Collins JH, Nanno S: The disulfide bonds of alpha1-acid glycoprotein. Biochemistry. 1974 Jun 18;13(13):2694-7. [PubMed Link Image]
  8. Schmid K, Kaufmann H, Isemura S, Bauer F, Emura J, Motoyama T, Ishiguro M, Nanno S: Structure of 1 -acid glycoprotein. The complete amino acid sequence, multiple amino acid substitutions, and homology with the immunoglobulins. Biochemistry. 1973 Jul 3;12(14):2711-24. [PubMed Link Image]
  9. Yuasa I, Umetsu K, Vogt U, Nakamura H, Nanba E, Tamaki N, Irizawa Y: Human orosomucoid polymorphism: molecular basis of the three common ORM1 alleles, ORM1*F1, ORM1*F2, and ORM1*S. Hum Genet. 1997 Mar;99(3):393-8. [PubMed Link Image]
Target 3 Drug References
  1. 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. [PubMed Link Image]
  2. 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. [PubMed Link Image]
  3. 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. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.