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Showing drug card for Diclofenac (DB00586)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-26 21:14:04
Primary Accession Number DB00586
Secondary Accession Number
  • APRD00527
Name Diclofenac
Drug Type
  • Small Molecule
Description A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt. [PubChem]
Synonyms
  1. Diclofenac Acid
  2. Diclofenac Potassium
  3. Diclofenac Sodium
  4. ISV-205
Brand Names
  1. Allvoran
  2. Apo-Diclo
  3. Assaren
  4. Benfofen
  5. Cataflam
  6. Delphimix
  7. Dichlofenac
  8. Dichronic
  9. Diclo-Phlogont
  10. Diclo-Puren
  11. Diclobenin
  12. Diclord
  13. Dicloreum
  14. Dolobasan
  15. Duravolten
  16. Dyloject
  17. Ecofenac
  18. Effekton
  19. Kriplex
  20. Neriodin
  21. Novapirina
  22. Novo-Difenac
  23. Novo-Difenac SR
  24. Nu-Diclo
  25. Pennsaid
  26. Primofenac
  27. ProSorb-D
  28. Prophenatin
  29. Rhumalgan
  30. Solaraze
  31. Solaraze T
  32. Tsudohmin
  33. Valetan
  34. Voldal
  35. Voltaren
  36. Voltaren Ophtha
  37. Voltaren Ophthalmic
  38. Voltaren Rapide
  39. Voltaren SR
  40. Voltaren-XR
  41. Voltarol
  42. Xenid
Brand Mixtures Not Available
Chemical IUPAC Name 2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetic acid
Chemical Formula C14H11Cl2NO2
Chemical Structure Structure
CAS Registry Number 15307-86-5
InChI Identifier InChI=1/C14H11Cl2NO2/c15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19/h1-7,17H,8H2,(H,18,19)/f/h18H
InChI Key DCOPUUMXTXDBNB-GPQMBLKYCR
KEGG Drug Not Available
KEGG Compound C01690 Link Image
PubChem Compound 3033 Link Image
PubChem Substance 4831 Link Image
ChEBI ID 4507 Link Image
PharmGKB ID PA449293 Link Image
HET ID DIF Link Image
GenBank ID Not Available
Drug ID Number [DIN] 02241225 Link Image
RxList Link http://www.rxlist.com/cgi/generic/diclofen.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Diclofenac Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference A. Sallman, R. Pfister, U.S. Pat. 3,558,690, (1971)
Average Molecular Weight 296.1490
Monoisotopic Molecular Weight 295.0167
State Solid
Melting Point 283-285oC
Experimental Water Solubility 50 mg/mL (sodium salt) [Sigma Aldrich] Source: PhysProp
Predicted Water Solubility 4.47e-03 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 3.9 Source: PhysProp
Predicted LogP 4.98 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.82 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 4.15
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 OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl
Canonical SMILES OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl
Drug Category
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Nonsteroidal Antiinflammatory Agents (NSAIDs)
ATC Codes
AHFS Codes
  • 28:08.04.08
  • 28:08.04.92
Indication For the acute and chronic treatment of signs and symptoms of osteoarthritis and rheumatoid arthritis.
Pharmacology Diclofenac is an acetic acid nonsteroidal antiinflammatory drug (NSAID) with analgesic and antipyretic properties. Diclofenac is used to treat pain, dysmenorrhea, ocular inflammation, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and actinic keratosis
Mechanism of Action The antiinflammatory effects of diclofenac are believed to be due to inhibition of both leukocyte migration and the enzyme cylooxygenase (COX-1 and COX-2), leading to the peripheral inhibition of prostaglandin synthesis. As prostaglandins sensitize pain receptors, inhibition of their synthesis is responsible for the analgesic effects of diclofenac. Antipyretic effects may be due to action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat dissipation.
Absorption Completely absorbed from the gastrointestinal tract.
Toxicity Symptoms of overdose include loss of consciousness, increased intracranial pressure, and aspiration pneumonitis. LD50=390mg/kg (orally in mice)
Protein Binding More than 99%
Biotransformation Hepatic
Half Life 2 hours
Dosage Forms
Form Route
Solution Ophthalmic
Solution Topical
Suppository Rectal
Tablet Oral
Tablet, coated Oral
Tablet, extended release Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Alendronate Increased risk of gastric toxicity
Anisindione The NSAID increases the anticoagulant effect
Cyclosporine Monitor for nephrotoxicity
Dicumarol The NSAID increases the anticoagulant effect
Rifampin Decreased levels/effect of the NSAID
Warfarin The NSAID increases the anticoagulant effect
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce irritation.
Pathways
Name SMPDB Link KEGG Link
Diclofenac Pathway SMP00093 Link Image
General References
  1. FitzGerald GA, Patrono C: The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med. 2001 Aug 9;345(6):433-42. [PubMed Link Image]
  2. Brater DC: Renal effects of cyclooxygyenase-2-selective inhibitors. J Pain Symptom Manage. 2002 Apr;23(4 Suppl):S15-20; discussion S21-3. [PubMed Link Image]
  3. Solomon DH, Avorn J, Sturmer T, Glynn RJ, Mogun H, Schneeweiss S: Cardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory drugs: high-risk subgroups and time course of risk. Arthritis Rheum. 2006 May;54(5):1378-89. [PubMed Link Image]
  4. Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C: Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006 Jun 3;332(7553):1302-8. [PubMed Link Image]
  5. Graham DJ: COX-2 inhibitors, other NSAIDs, and cardiovascular risk: the seduction of common sense. JAMA. 2006 Oct 4;296(13):1653-6. Epub 2006 Sep 12. [PubMed Link Image]
  6. Drugs.com Link Image
  7. [PubMed Link Image]
  8. Wikipedia Link Image
  9. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 2C19 (CYP2C19)
  2. Cytochrome P450 1A2 (CYP1A2)
  3. Cytochrome P450 2C8 (CYP2C8)
  4. Cytochrome P450 2C9 (CYP2C9)
  5. Cytochrome P450 2D6 (CYP2D6)
  6. Glucuronosyltransferase
Targets
  1. Prostaglandin G/H synthase 1
  2. Prostaglandin G/H synthase 2
  3. Transthyretin
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 2C19 (CYP2C19)
Enzyme 1 Gene Name CYP2C19
Enzyme 1 SwissProt ID P33261 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P33261|CP2CJ_HUMAN Cytochrome P450 2C19 (EC 1.14.13.80)
MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDVSKSLTNLSKI
YGPVFTLYFGLERMVVLHGYEVVKEALIDLGEEFSGRGHFPLAERANRGFGIVFSNGKRW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFQKRFDYKDQQFLNLMEKLNENIRIVSTPWIQICNNFPTIIDYFPGTHNKLLKNLAFM
ESDILEKVKEHQESMDINNPRDFIDCFLIKMEKEKQNQQSEFTIENLVITAADLLGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVVGRNRSPCMQDRGHMPYTDAVVHEVQRYID
LIPTSLPHAVTCDVKFRNYLIPKGTTILTSLTSVLHDNKEFPNPEMFDPRHFLDEGGNFK
KSNYFMPFSAGKRICVGEGLARMELFLFLTFILQNFNLKSLIDPKDLDTTPVVNGFASVP
PFYQLCFIPV
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Cytochrome P450 1A2 (CYP1A2)
Enzyme 2 Gene Name CYP1A2
Enzyme 2 SwissProt ID P05177 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >P05177|CP1A2_HUMAN Cytochrome P450 1A2 - Homo sapiens (Human).
MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPLLGHVLTLGKN
PHLALSRMSQRYGDVLQIRIGSTPVLVLSRLDTIRQALVRQGDDFKGRPDLYTSTLITDG
QSLTFSTDSGPVWAARRRLAQNALNTFSIASDPASSSSCYLEEHVSKEAKALISRLQELM
AGPGHFDPYNQVVVSVANVIGAMCFGQHFPESSDEMLSLVKNTHEFVETASSGNPLDFFP
ILRYLPNPALQRFKAFNQRFLWFLQKTVQEHYQDFDKNSVRDITGALFKHSKKGPRASGN
LIPQEKIVNLVNDIFGAGFDTVTTAISWSLMYLVTKPEIQRKIQKELDTVIGRERRPRLS
DRPQLPYLEAFILETFRHSSFLPFTIPHSTTRDTTLNGFYIPKKCCVFVNQWQVNHDPEL
WEDPSEFRPERFLTADGTAINKPLSEKMMLFGMGKRRCIGEVLAKWEIFLFLAILLQQLE
FSVPPGVKVDLTPIYGLTMKHARCEHVQARRFSIN
Phase 1 Metabolizing Enzyme 3 [top]
Enzyme 3 Name Cytochrome P450 2C8 (CYP2C8)
Enzyme 3 Gene Name CYP2C8
Enzyme 3 SwissProt ID P10632 Link Image
Enzyme 3 SNPs SNPJam Report Link Image
Enzyme 3 Protein Sequence >sp|P10632|CP2C8_HUMAN Cytochrome P450 2C8 (EC 1.14.14.1)
MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDICKSFTNFSKV
YGPVFTVYFGMNPIVVFHGYEAVKEALIDNGEEFSGRGNSPISQRITKGLGIISSNGKRW
KEIRRFSLTTLRNFGMGKRSIEDRVQEEAHCLVEELRKTKASPCDPTFILGCAPCNVICS
VVFQKRFDYKDQNFLTLMKRFNENFRILNSPWIQVCNNFPLLIDCFPGTHNKVLKNVALT
RSYIREKVKEHQASLDVNNPRDFIDCFLIKMEQEKDNQKSEFNIENLVGTVADLFVAGTE
TTSTTLRYGLLLLLKHPEVTAKVQEEIDHVIGRHRSPCMQDRSHMPYTDAVVHEIQRYSD
LVPTGVPHAVTTDTKFRNYLIPKGTTIMALLTSVLHDDKEFPNPNIFDPGHFLDKNGNFK
KSDYFMPFSAGKRICAGEGLARMELFLFLTTILQNFNLKSVDDLKNLNTTAVTKGIVSLP
PSYQICFIPV
Phase 1 Metabolizing Enzyme 4 [top]
Enzyme 4 Name Cytochrome P450 2C9 (CYP2C9)
Enzyme 4 Gene Name CYP2C9
Enzyme 4 SwissProt ID P11712 Link Image
Enzyme 4 SNPs SNPJam Report Link Image
Enzyme 4 Protein Sequence >sp|P11712|CP2C9_HUMAN Cytochrome P450 2C9 (EC 1.14.13.80)
MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKV
YGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFM
KSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYID
LLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFK
KSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVP
PFYQLCFIPV
Phase 1 Metabolizing Enzyme 5 [top]
Enzyme 5 Name Cytochrome P450 2D6 (CYP2D6)
Enzyme 5 Gene Name CYP2D6
Enzyme 5 SwissProt ID P10635 Link Image
Enzyme 5 SNPs SNPJam Report Link Image
Enzyme 5 Protein Sequence >sp|P10635|CP2D6_HUMAN Cytochrome P450 2D6 (EC 1.14.14.1)
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQ
LRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVF
LARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDK
AVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKV
LRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVA
DLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVI
HEVQRFGDIVPLGMTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHF
LDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGV
FAFLVSPSPYELCAVPR
Phase 1 Metabolizing Enzyme 6 [top]
Enzyme 6 Name Glucuronosyltransferase
Enzyme 6 Gene Name UGT1A1
Enzyme 6 SwissProt ID P22309 Link Image
Enzyme 6 SNPs SNPJam Report Link Image
Enzyme 6 Protein Sequence >sp|P22309|UD11_HUMAN UDP-glucuronosyltransferase 1-1 precursor
MAVESQGGRPLVLGLLLCVLGPVVSHAGKILLIPVDGSHWLSMLGAIQQLQQRGHEIVVL
APDASLYIRDGAFYTLKTYPVPFQREDVKESFVSLGHNVFENDSFLQRVIKTYKKIKKDS
AMLLSGCSHLLHNKELMASLAESSFDVMLTDPFLPCSPIVAQYLSLPTVFFLHALPCSLE
FEATQCPNPFSYVPRPLSSHSDHMTFLQRVKNMLIAFSQNFLCDVVYSPYATLASEFLQR
EVTVQDLLSSASVWLFRSDFVKDYPRPIMPNMVFVGGINCLHQNPLSQEFEAYINASGEH
GIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDL
LGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTS
EDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHD
LTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
Drug Target 1 [top]
Target 1 ID 20
Target 1 Name Prostaglandin G/H synthase 1
Target 1 Synonyms
  1. COX-1
  2. Cyclooxygenase- 1
  3. EC 1.14.99.1
  4. PGH synthase 1
  5. PGHS-1
  6. PHS 1
  7. Prostaglandin G/H synthase 1 precursor
  8. Prostaglandin H2 synthase 1
  9. Prostaglandin-endoperoxide synthase 1
Target 1 Gene Name PTGS1
Target 1 Protein Sequence >Prostaglandin G/H synthase 1 precursor
MSRSLLLRFLLFLLLLPPLPVLLADPGAPTPVNPCCYYPCQHQGICVRFGLDRYQCDCTR
TGYSGPNCTIPGLWTWLRNSLRPSPSFTHFLLTHGRWFWEFVNATFIREMLMRLVLTVRS
NLIPSPPTYNSAHDYISWESFSNVSYYTRILPSVPKDCPTPMGTKGKKQLPDAQLLARRF
LLRRKFIPDPQGTNLMFAFFAQHFTHQFFKTSGKMGPGFTKALGHGVDLGHIYGDNLERQ
YQLRLFKDGKLKYQVLDGEMYPPSVEEAPVLMHYPRGIPPQSQMAVGQEVFGLLPGLMLY
ATLWLREHNRVCDLLKAEHPTWGDEQLFQTTRLILIGETIKIVIEEYVQQLSGYFLQLKF
DPELLFGVQFQYRNRIAMEFNHLYHWHPLMPDSFKVGSQEYSYEQFLFNTSMLVDYGVEA
LVDAFSRQIAGRIGGGRNMDHHILHVAVDVIRESREMRLQPFNEYRKRFGMKPYTSFQEL
VGEKEMAAELEELYGDIDALEFYPGLLLEKCHPNSIFGESMIEIGAPFSLKGLLGNPICS
PEYWKPSTFGGEVGFNIVKTATLKKLVCLNTKTCPYVSFRVPDASQDDGPAVERPSTEL
Target 1 Number of Residues 608
Target 1 Molecular Weight 68657
Target 1 Theoretical pI 7.39
Target 1 GO Classification
Function
antioxidant activity
peroxidase activity
Process
Not Available
Component
Not Available
Target 1 General Function Involved in peroxidase activity
Target 1 Specific Function May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells
Target 1 Pathways
Name SMPDB Link KEGG Link
Prostaglandin and leukotriene metabolism map00590 Link Image
Target 1 Reactions
  • arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O
Target 1 Pfam Domain Function
Target 1 Signals
  • 1-23
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 387018 Link Image
Target 1 UniProtKB/Swiss-Prot ID P23219 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name PGH1_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Microsome
  • microsomal membrane
  • peripheral membrane protein
Target 1 Gene Sequence >1800 bp
ATGAGCCGGAGTCTCTTGCTCCGGTTCTTGCTGTTGCTGCTCCTGCTCCCGCCGCTCCCC
GTCCTGCTCGCGGACCCAGGGGCGCCCACGCCAGTGAATCCCTGTTGTTACTATCCATGC
CAGCACCAGGGCATCTGTGTCCGCTTCGGCCTTGACCGCTACCAGTGTGACTGCACCCGC
ACGGGCTATTCCGGCCCCAACTGCACCATCCCTGGCCTGTGGACCTGGCTCCGGAATTCA
CTGCGGCCCAGCCCCTCTTTCACCCACTTCCTGCTCACTCACGGGCGCTGGTTCTGGGAG
TTTGTCAATGCCACCTTCATCCGAGAGATGCTCATGCTCCTGGTACTCACAGTGCGCTCC
AACCTTATCCCCAGTCCCCCCACCTACAACTCTGCACATGACTACATCAGCTGGGAGTCT
TTCTCCAACGTGAGCTATTACACTCGTATTCTGCCCTCTGTGCCTAAAGATTGCCCCACA
CCCATGGGAACCAAAGGGAAGAAGCAGTTGCCAGATGCCCAGCTCCTGGCCCGCCGCTTC
CTGCTCAGGAGGAAGTTCATACCTGACCCCCAAGGCACCAACCTCATGTTTGCCTTCTTT
GCACAACACTTCACCCACCAGTTCTTCAAAACTTCTGGCAAGATGGGTCCTGGCTTCACC
AAGGCCTTGGGCCATGGGGTAGACCTCGGCCACATTTATGGAGACAATCTGGAGCGTCAG
TATCAACTGCGGCTCTTTAAGGATGGGAAACTCAAGTACCAGGTGCTGGATGGAGAAATG
TACCCGCCCTCGGTAGAAGAGGCGCCTGTGTTGATGCACTACCCCCGAGGCATCCCGCCC
CAGAGCCAGATGGCTGTGGGCCAGGAGGTGTTTGGGCTGCTTCCTGGGCTCATGCTGTAT
GCCACGCTCTGGCTACGTGAGCACAACCGTGTGTGTGACCTGCTGAAGGCTGAGCACCCC
ACCTGGGGCGATGAGCAGCTTTTCCAGACGACCCGCCTCATCCTCATAGGGGAGACCATC
AAGATTGTCATCGAGGAGTACGTGCAGCAGCTGAGTGGCTATTTCCTGCAGCTGAAATTT
GACCCAGAGCTGCTGTTCGGTGTCCAGTTCCAATACCGCAACCGCATTGCCACGGAGTTC
AACCATCTCTACCACTGGCACCCCCTCATGCCTGACTCCTTCAAGGTGGGCTCCCAGGAG
TACAGCTACGAGCAGTTCTTGTTCAACACCTCCATGTTGGTGGACTATGGGGTTGAGGCC
CTGGTGGATGCCTTCTCTCGCCAGATTGCTGGCCGGATCGGTGGGGGCAGGAACATGGAC
CACCACATCCTGCATGTGGCTGTGGATGTCATCAGGGAGTCTCGGGAGATGCGGCTGCAG
CCCTTCAATGAGTACCGCAAGAGGTTTGGCATGAAACCCTACACCTCCTTCCAGGAGCTC
GTAGGAGAGAAGGAGATGGCAGCAGAGTTGGAGGAATTGTATGGAGACATTGATGCGTTG
GAGTTCTACCCTGGACTGCTTCTTGAAAAGTGCCATCCAAACTCTATCTTTGGGGAGAGT
ATGATAGAGATTGGGGCTCCCTTTTCCCTCAAGGGTCTCCTAGGGAATCCCATCTGTTCT
CCGGAGTACTGGAAGCCGAGCACATTTGGCGGCGAGGTGGGCTTTAACATTGTCAAGACG
GCCACACTGAAGAAGCTGGTCTGCCTCAACACCAAGACCTGTCCCTACGTTTCCTTCCGT
GTGCCGGATGCCAGTCAGGATGATGGGCCTGCTGTGGAGCGACCATCCACAGAGCTCTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID PTGS1 Link Image
Target 1 GenAtlas ID PTGS1 Link Image
Target 1 HGNC ID HGNC:9604 Link Image
Target 1 Chromosome Location 9
Target 1 Locus 9q32-q33.3
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Diaz A, Reginato AM, Jimenez SA: Alternative splicing of human prostaglandin G/H synthase mRNA and evidence of differential regulation of the resulting transcripts by transforming growth factor beta 1, interleukin 1 beta, and tumor necrosis factor alpha. J Biol Chem. 1992 May 25;267(15):10816-22. [PubMed Link Image]
  2. Takahashi Y, Ueda N, Yoshimoto T, Yamamoto S, Yokoyama C, Miyata A, Tanabe T, Fuse I, Hattori A, Shibata A: Immunoaffinity purification and cDNA cloning of human platelet prostaglandin endoperoxide synthase (cyclooxygenase). Biochem Biophys Res Commun. 1992 Jan 31;182(2):433-8. [PubMed Link Image]
  3. Funk CD, Funk LB, Kennedy ME, Pong AS, Fitzgerald GA: Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment. FASEB J. 1991 Jun;5(9):2304-12. [PubMed Link Image]
  4. Yokoyama C, Tanabe T: Cloning of human gene encoding prostaglandin endoperoxide synthase and primary structure of the enzyme. Biochem Biophys Res Commun. 1989 Dec 15;165(2):888-94. [PubMed Link Image]
Target 1 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  2. Calkin AC, Sudhir K, Honisett S, Williams MR, Dawood T, Komesaroff PA: Rapid potentiation of endothelium-dependent vasodilation by estradiol in postmenopausal women is mediated via cyclooxygenase 2. J Clin Endocrinol Metab. 2002 Nov;87(11):5072-5. [PubMed Link Image]
  3. Kirchheiner J, Meineke I, Steinbach N, Meisel C, Roots I, Brockmoller J: Pharmacokinetics of diclofenac and inhibition of cyclooxygenases 1 and 2: no relationship to the CYP2C9 genetic polymorphism in humans. Br J Clin Pharmacol. 2003 Jan;55(1):51-61. [PubMed Link Image]
  4. Kampfer H, Brautigam L, Geisslinger G, Pfeilschifter J, Frank S: Cyclooxygenase-1-coupled prostaglandin biosynthesis constitutes an essential prerequisite for skin repair. J Invest Dermatol. 2003 May;120(5):880-90. [PubMed Link Image]
  5. Chavez ML, DeKorte CJ: Valdecoxib: a review. Clin Ther. 2003 Mar;25(3):817-51. [PubMed Link Image]
  6. Hinz B, Rau T, Auge D, Werner U, Ramer R, Rietbrock S, Brune K: Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac. Clin Pharmacol Ther. 2003 Sep;74(3):222-35. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 290
Target 2 Name Prostaglandin G/H synthase 2
Target 2 Synonyms
  1. COX-2
  2. Cyclooxygenase- 2
  3. EC 1.14.99.1
  4. PGH synthase 2
  5. PGHS-2
  6. PHS II
  7. Prostaglandin G/H synthase 2 precursor
  8. Prostaglandin H2 synthase 2
  9. Prostaglandin-endoperoxide synthase 2
Target 2 Gene Name PTGS2
Target 2 Protein Sequence >Prostaglandin G/H synthase 2 precursor
MLARALLLCAVLALSHTANPCCSHPCQNRGVCMSVGFDQYKCDCTRTGFYGENCSTPEFL
TRIKLFLKPTPNTVHYILTHFKGFWNVVNNIPFLRNAIMSYVLTSRSHLIDSPPTYNADY
GYKSWEAFSNLSYYTRALPPVPDDCPTPLGVKGKKQLPDSNEIVEKLLLRRKFIPDPQGS
NMMFAFFAQHFTHQFFKTDHKRGPAFTNGLGHGVDLNHIYGETLARQRKLRLFKDGKMKY
QIIDGEMYPPTVKDTQAEMIYPPQVPEHLRFAVGQEVFGLVPGLMMYATIWLREHNRVCD
VLKQEHPEWGDEQLFQTSRLILIGETIKIVIEDYVQHLSGYHFKLKFDPELLFNKQFQYQ
NRIAAEFNTLYHWHPLLPDTFQIHDQKYNYQQFIYNNSILLEHGITQFVESFTRQIAGRV
AGGRNVPPAVQKVSQASIDQSRQMKYQSFNEYRKRFMLKPYESFEELTGEKEMSAELEAL
YGDIDAVELYPALLVEKPRPDAIFGETMVEVGAPFSLKGLMGNVICSPAYWKPSTFGGEV
GFQIINTASIQSLICNNVKGCPFTSFSVPDPELIKTVTINASSSRSGLDDINPTVLLKER
STEL
Target 2 Number of Residues 614
Target 2 Molecular Weight 68997
Target 2 Theoretical pI 7.41
Target 2 GO Classification
Function
antioxidant activity
peroxidase activity
Process
Not Available
Component
Not Available
Target 2 General Function Involved in peroxidase activity
Target 2 Specific Function May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity
Target 2 Pathways
Name SMPDB Link KEGG Link
Prostaglandin and leukotriene metabolism map00590 Link Image
Target 2 Reactions
  • arachidonate + AH2 + 2 O2 = prostaglandin H2 + A + H2O
Target 2 Pfam Domain Function
Target 2 Signals
  • 1-17
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 291988 Link Image
Target 2 UniProtKB/Swiss-Prot ID P35354 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name PGH2_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Microsome
  • microsomal membrane
  • peripheral membrane protein
Target 2 Gene Sequence >1815 bp
ATGCTCGCCCGCGCCCTGCTGCTGTGCGCGGTCCTGGCGCTCAGCCATACAGCAAATCCT
TGCTGTTCCCACCCATGTCAAAACCGAGGTGTATGTATGAGTGTGGGATTTGACCAGTAT
AAGTGCGATTGTACCCGGACAGGATTCTATGGAGAAAACTGCTCAACACCGGAATTTTTG
ACAAGAATAAAATTATTTCTGAAACCCACTCCAAACACAGTGCACTACATACTTACCCAC
TTCAAGGGATTTTGGAACGTTGTGAATAACATTCCCTTCCTTCGAAATGCAATTATGAGT
TATGTGTTGACATCCAGATCACATTTGATTGACAGTCCACCAACTTACAATGCTGACTAT
GGCTACAAAAGCTGGGAAGCCTTCTCTAACCTCTCCTATTATACTAGAGCCCTTCCTCCT
GTGCCTGATGATTGCCCGACTCCCTTGGGTGTCAAAGGTAAAAAGCAGCTTCCTGATTCA
AATGAGATTGTGGAAAAATTGCTTCTAAGAAGAAAGTTCATCCCTGATCCCCAGGGCTCA
AACATGATGTTTGCATTCTTTGCCCAGCACTTCACGCATCAGTTTTTCAAGACAGATCAT
AAGCGAGGGCCAGCTTTCACCAACGGGCTGGGCCATGGGGTGGACTTAAATCATATTTAC
GGTGAAACTCTGGCTAGACAGCGTAAACTGCGCCTTTTCAAGGATGGAAAAATGAAATAT
CAGATAATTGATGGAGAGATGTATCCTCCCACAGTCAAAGATACTCAGGCAGAGATGATC
TACCCTCCTCAAGTCCCTGAGCATCTACGGTTTGCTGTGGGGCAGGAGGTCTTTGGTCTG
GTGCCTGGTCTGATGATGTATGCCACAATCTGGCTGCGGGAACACAACAGAGTATGCGAT
GTGCTTAAACAGGAGCATCCTGAATGGGGTGATGAGCAGTTGTTCCAGACAAGCAGGCTA
ATACTGATAGGAGAGACTATTAAGATTGTGATTGAAGATTATGTGCAACACTTGAGTGGC
TATCACTTCAAACTGAAATTTGACCCAGAACTACTTTTCAACAAACAATTCCAGTACCAA
AATCGTATTGCTGCTGAATTTAACACCCTCTATCACTGGCATCCCCTTCTGCCTGACACC
TTTCAAATTCATGACCAGAAATACAACTATCAACAGTTTATCTACAACAACTCTATATTG
CTGGAACATGGAATTACCCAGTTTGTTGAATCATTCACCAGGCAAATTGCTGGCAGGGTT
GCTGGTGGTAGGAATGTTCCACCCGCAGTACAGAAAGTATCACAGGCTTCCACTGACCAG
AGCAGGCAGATGAAATACCAGTCTTTTAATGAGTACCGCAAACGCTTTATGCTGAAGCCC
TATGAATCATTTGAAGAACTTACAGGAGAAAAGGAAATGTCTGCAGAGTTGGAAGCACTC
TATGGTGACATCGATGCTGTGGAGCTGTATCCTGCCCTTCTGGTAGAAAAGCCTCGGCCA
GATGCCATCTTTGGTGAAACCATGGTAGAAGTTGGAGCACCATTCTCCTTGAAAGGACTT
ATGGGTAATGTTATATGTTCTCCTGCCTACTGGAAGCCAAGCACTTTTGGTGGAGAAGTG
GGTTTTCAAATCATCAACACTGCCTCAATTCAGTCTCTCATCTGCAATAACGTGAAGGGC
TGTCCCTTTACTTCATTCAGTGTTCCAGATCCAGAGCTCATTAAAACAGTCACCATCAAT
GCAAGTTCTTCCCGCTCCGGACTAGATGATATCAATCCCACAGTACTACTAAAAGAACGT
TCGACTGAACTGTAG
Target 2 GenBank Gene ID
Target 2 GeneCard ID PTGS2 Link Image
Target 2 GenAtlas ID PTGS2 Link Image
Target 2 HGNC ID HGNC:9605 Link Image
Target 2 Chromosome Location 1
Target 2 Locus 1q25.2-q25.3
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Hla T, Neilson K: Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7384-8. [PubMed Link Image]
  2. Appleby SB, Ristimaki A, Neilson K, Narko K, Hla T: Structure of the human cyclo-oxygenase-2 gene. Biochem J. 1994 Sep 15;302 ( Pt 3):723-7. [PubMed Link Image]
  3. Kosaka T, Miyata A, Ihara H, Hara S, Sugimoto T, Takeda O, Takahashi E, Tanabe T: Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxide synthase 2. Eur J Biochem. 1994 May 1;221(3):889-97. [PubMed Link Image]
  4. Jones DA, Carlton DP, McIntyre TM, Zimmerman GA, Prescott SM: Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines. J Biol Chem. 1993 Apr 25;268(12):9049-54. [PubMed Link Image]
Target 2 Drug References
  1. Kirchheiner J, Meineke I, Steinbach N, Meisel C, Roots I, Brockmoller J: Pharmacokinetics of diclofenac and inhibition of cyclooxygenases 1 and 2: no relationship to the CYP2C9 genetic polymorphism in humans. Br J Clin Pharmacol. 2003 Jan;55(1):51-61. [PubMed Link Image]
  2. Blomme EA, Chinn KS, Hardy MM, Casler JJ, Kim SH, Opsahl AC, Hall WA, Trajkovic D, Khan KN, Tripp CS: Selective cyclooxygenase-2 inhibition does not affect the healing of cutaneous full-thickness incisional wounds in SKH-1 mice. Br J Dermatol. 2003 Feb;148(2):211-23. [PubMed Link Image]
  3. Beubler E: [Pharmacology of cyclooxygenase 2 inhibition] Wien Med Wochenschr. 2003;153(5-6):95-9. [PubMed Link Image]
  4. Chavez ML, DeKorte CJ: Valdecoxib: a review. Clin Ther. 2003 Mar;25(3):817-51. [PubMed Link Image]
  5. Rowlinson SW, Kiefer JR, Prusakiewicz JJ, Pawlitz JL, Kozak KR, Kalgutkar AS, Stallings WC, Kurumbail RG, Marnett LJ: A novel mechanism of cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385. J Biol Chem. 2003 Nov 14;278(46):45763-9. Epub 2003 Aug 18. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 373
Target 3 Name Transthyretin
Target 3 Synonyms
  1. ATTR
  2. Prealbumin
  3. TBPA
  4. TTR
  5. Transthyretin precursor
Target 3 Gene Name TTR
Target 3 Protein Sequence >Transthyretin precursor
MASHRLLLLCLAGLVFVSEAGPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDT
WEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDS
GPRRYTIAALLSPYSYSTTAVVTNPKE
Target 3 Number of Residues 149
Target 3 Molecular Weight 15887
Target 3 Theoretical pI 5.58
Target 3 GO Classification
Function
binding
steroid binding
transporter activity
carrier activity
Process
physiological process
cellular physiological process
transport
Component
Not Available
Target 3 General Function Involved in steroid binding
Target 3 Specific Function Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • 1-20
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 189582 Link Image
Target 3 UniProtKB/Swiss-Prot ID P02766 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name TTHY_HUMAN Link Image
Target 3 PDB ID 1KED Link Image
Target 3 PDB File Show
Target 3 3D Structure
Target 3 Cellular Location
  • Secreted protein
Target 3 Gene Sequence >444 bp
ATGGCTTCTCATCGTCTGCTCCTCCTCTGCCTTGCTGGACTGGTATTTGTGTCTGAGGCT
GGCCCTACGGGCACCGGTGAATCCAAGTGTCCTCTGATGGTCAAAGTTCTAGATGCTGTC
CGAGGCAGTCCTGCCATCAATGTGGCCGTGCATGTGTTCAGAAAGGCTGCTGATGACACC
TGGGAGCCATTTGCCTCTGGGAAAACCAGTGAGTCTGGAGAGCTGCATGGGCTCACAACT
GAGGAGGAATTTGTAGAAGGGATATACAAAGTGGAAATAGACACCAAATCTTACTGGAAG
GCACTTGGCATCTCCCCATTCCATGAGCATGCAGAGGTGGTATTCACAGCCAACGACTCC
GGCCCCCGCCGCTACACCATTGCCGCCCTGCTGAGCCCCTACTCCTATTCCACCACGGCT
GTCGTCACCAATCCCAAGGAATGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID TTR Link Image
Target 3 GenAtlas ID TTR Link Image
Target 3 HGNC ID HGNC:12405 Link Image
Target 3 Chromosome Location 18
Target 3 Locus 18q12.1
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Naylor HM, Newcomer ME: The structure of human retinol-binding protein (RBP) with its carrier protein transthyretin reveals an interaction with the carboxy terminus of RBP. Biochemistry. 1999 Mar 2;38(9):2647-53. [PubMed Link Image]
  2. Klabunde T, Petrassi HM, Oza VB, Raman P, Kelly JW, Sacchettini JC: Rational design of potent human transthyretin amyloid disease inhibitors. Nat Struct Biol. 2000 Apr;7(4):312-21. [PubMed Link Image]
  3. Nakamura M, Hamidi Asl K, Benson MD: A novel variant of transthyretin (Glu89Lys) associated with familial amyloidotic polyneuropathy. Amyloid. 2000 Mar;7(1):46-50. [PubMed Link Image]
  4. de Carvalho M, Moreira P, Evangelista T, Ducla-Soares JL, Bento M, Fernandes R, Saraiva MJ: New transthyretin mutation V28M in a Portuguese kindred with amyloid polyneuropathy. Muscle Nerve. 2000 Jul;23(7):1016-21. [PubMed Link Image]
  5. 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]
  6. Blevins G, Macaulay R, Harder S, Fladeland D, Yamashita T, Yazaki M, Hamidi Asl K, Benson MD, Donat JR: Oculoleptomeningeal amyloidosis in a large kindred with a new transthyretin variant Tyr69His. Neurology. 2003 May 27;60(10):1625-30. [PubMed Link Image]
  7. Almeida MR, Ferlini A, Forabosco A, Gawinowicz M, Costa PP, Salvi F, Plasmati R, Tassinari CA, Altland K, Saraiva MJ: Two transthyretin variants (TTR Ala-49 and TTR Gln-89) in two Sicilian kindreds with hereditary amyloidosis. Hum Mutat. 1992;1(3):211-5. [PubMed Link Image]
  8. Jacobson DR, McFarlin DE, Kane I, Buxbaum JN: Transthyretin Pro55, a variant associated with early-onset, aggressive, diffuse amyloidosis with cardiac and neurologic involvement. Hum Genet. 1992 May;89(3):353-6. [PubMed Link Image]
  9. Uemichi T, Murrell JR, Zeldenrust S, Benson MD: A new mutant transthyretin (Arg 10) associated with familial amyloid polyneuropathy. J Med Genet. 1992 Dec;29(12):888-91. [PubMed Link Image]
  10. Izumoto S, Younger D, Hays AP, Martone RL, Smith RT, Herbert J: Familial amyloidotic polyneuropathy presenting with carpal tunnel syndrome and a new transthyretin mutation, asparagine 70. Neurology. 1992 Nov;42(11):2094-102. [PubMed Link Image]
  11. 1517749 Kametani F, Ikeda S, Yanagisawa N, Ishi T, Hanyu N: Characterization of a transthyretin-related amyloid fibril protein from cerebral amyloid angiopathy in type I familial amyloid polyneuropathy. J Neurol Sci. 1992 Apr;108(2):178-83.
  12. 1520326 Murakami T, Atsumi T, Maeda S, Tanase S, Ishikawa K, Mita S, Kumamoto T, Araki S, Ando M: A novel transthyretin mutation at position 30 (Leu for Val) associated with familial amyloidotic polyneuropathy. Biochem Biophys Res Commun. 1992 Aug 31;187(1):397-403.
  13. 1520336 Nishi H, Kimura A, Harada H, Hayashi Y, Nakamura M, Sasazuki T: Novel variant transthyretin gene (Ser50 to Ile) in familial cardiac amyloidosis. Biochem Biophys Res Commun. 1992 Aug 31;187(1):460-6.
  14. 1544214 Jones LA, Skare JC, Cohen AS, Harding JA, Milunsky A, Skinner M: Familial amyloidotic polyneuropathy: a new transthyretin position 30 mutation (alanine for valine) in a family of German descent. Clin Genet. 1992 Feb;41(2):70-3.
  15. 1570831 Saraiva MJ, Almeida Mdo R, Sherman W, Gawinowicz M, Costa P, Costa PP, Goodman DS: A new transthyretin mutation associated with amyloid cardiomyopathy. Am J Hum Genet. 1992 May;50(5):1027-30.
  16. 1656975 Saeki Y, Ueno S, Yorifuji S, Sugiyama Y, Ide Y, Matsuzawa Y: New mutant gene (transthyretin Arg 58) in cases with hereditary polyneuropathy detected by non-isotope method of single-strand conformation polymorphism analysis. Biochem Biophys Res Commun. 1991 Oct 15;180(1):380-5.
  17. 1666289 Gu JR, Jiang HQ, He LP, Li DZ, Zhou XM, Dai WL, Qian LF, Chen YQ, Schweinfest C, Papas T: Transthyretin (prealbumin) gene in human primary hepatic cancer. Sci China B. 1991 Nov;34(11):1312-8.
  18. 1734866 Murakami T, Maeda S, Yi S, Ikegawa S, Kawashima E, Onodera S, Shimada K, Araki S: A novel transthyretin mutation associated with familial amyloidotic polyneuropathy. Biochem Biophys Res Commun. 1992 Jan 31;182(2):520-6.
  19. 1877623 Harrison HH, Gordon ED, Nichols WC, Benson MD: Biochemical and clinical characterization of prealbuminCHICAGO: an apparently benign variant of serum prealbumin (transthyretin) discovered with high-resolution two-dimensional electrophoresis. Am J Med Genet. 1991 Jun 15;39(4):442-52.
  20. 1932142 Harding J, Skare J, Skinner M: A second transthyretin mutation at position 33 (Leu/Phe) associated with familial amyloidotic polyneuropathy. Biochim Biophys Acta. 1991 Oct 21;1097(3):183-6.
  21. 1979335 Moses AC, Rosen HN, Moller DE, Tsuzaki S, Haddow JE, Lawlor J, Liepnieks JJ, Nichols WC, Benson MD: A point mutation in transthyretin increases affinity for thyroxine and produces euthyroid hyperthyroxinemia. J Clin Invest. 1990 Dec;86(6):2025-33.
  22. 1997217 Skare JC, Milunsky JM, Milunsky A, Skare IB, Cohen AS, Skinner M: A new transthyretin variant from a patient with familial amyloidotic polyneuropathy has asparagine substituted for histidine at position 90. Clin Genet. 1991 Jan;39(1):6-12.
  23. 2015890 Christmanson L, Betsholtz C, Gustavsson A, Johansson B, Sletten K, Westermark P: The transthyretin cDNA sequence is normal in transthyretin-derived senile systemic amyloidosis. FEBS Lett. 1991 Apr 9;281(1-2):177-80.
  24. 201845 Blake CC, Oatley SJ: Protein-DNA and protein-hormone interactions in prealbumin: a model of the thyroid hormone nuclear receptor? Nature. 1977 Jul 14;268(5616):115-20.
  25. 2046936 Ii S, Minnerath S, Ii K, Dyck PJ, Sommer SS: Two-tiered DNA-based diagnosis of transthyretin amyloidosis reveals two novel point mutations. Neurology. 1991 Jun;41(6):893-8.
  26. 2161654 Ueno S, Uemichi T, Yorifuji S, Tarui S: A novel variant of transthyretin (Tyr114 to Cys) deduced from the nucleotide sequences of gene fragments from familial amyloidotic polyneuropathy in Japanese sibling cases. Biochem Biophys Res Commun. 1990 May 31;169(1):143-7.
  27. 2363717 Ueno S, Uemichi T, Takahashi N, Soga F, Yorifuji S, Tarui S: Two novel variants of transthyretin identified in Japanese cases with familial amyloidotic polyneuropathy: transthyretin (Glu42 to Gly) and transthyretin (Ser50 to Arg). Biochem Biophys Res Commun. 1990 Jun 29;169(3):1117-21.
  28. 2891727 Wallace MR, Dwulet FE, Williams EC, Conneally PM, Benson MD: Identification of a new hereditary amyloidosis prealbumin variant, Tyr-77, and detection of the gene by DNA analysis. J Clin Invest. 1988 Jan;81(1):189-93.
  29. 2990465 Wallace MR, Naylor SL, Kluve-Beckerman B, Long GL, McDonald L, Shows TB, Benson MD: Localization of the human prealbumin gene to chromosome 18. Biochem Biophys Res Commun. 1985 Jun 28;129(3):753-8.
  30. 2995367 Tsuzuki T, Mita S, Maeda S, Araki S, Shimada K: Structure of the human prealbumin gene. J Biol Chem. 1985 Oct 5;260(22):12224-7.
  31. 3022108 Maeda S, Mita S, Araki S, Shimada K: Structure and expression of the mutant prealbumin gene associated with familial amyloidotic polyneuropathy. Mol Biol Med. 1986 Aug;3(4):329-38.
  32. 3135807 Cornwell GG 3rd, Sletten K, Johansson B, Westermark P: Evidence that the amyloid fibril protein in senile systemic amyloidosis is derived from normal prealbumin. Biochem Biophys Res Commun. 1988 Jul 29;154(2):648-53.
  33. 3675594 Strahler JR, Rosenblum BB, Hanash SM: Identification and characterization of a human transthyretin variant. Biochem Biophys Res Commun. 1987 Oct 14;148(1):471-7.
  34. 3722385 Wallace MR, Dwulet FE, Conneally PM, Benson MD: Biochemical and molecular genetic characterization of a new variant prealbumin associated with hereditary amyloidosis. J Clin Invest. 1986 Jul;78(1):6-12.
  35. 3818577 Mita S, Maeda S, Shimada K, Araki S: Analyses of prealbumin mRNAs in individuals with familial amyloidotic polyneuropathy. J Biochem (Tokyo). 1986 Nov;100(5):1215-22.
  36. 4044580 Soprano DR, Herbert J, Soprano KJ, Schon EA, Goodman DS: Demonstration of transthyretin mRNA in the brain and other extrahepatic tissues in the rat. J Biol Chem. 1985 Sep 25;260(21):11793-8.
  37. 4054629 Sasaki H, Yoshioka N, Takagi Y, Sakaki Y: Structure of the chromosomal gene for human serum prealbumin. Gene. 1985;37(1-3):191-7.
  38. 4216640 Blake CC, Geisow MJ, Swan ID, Rerat C, Rerat B: Strjcture of human plasma prealbumin at 2-5 A resolution. A preliminary report on the polypeptide chain conformation, quaternary structure and thyroxine binding. J Mol Biol. 1974 Sep 5;88(1):1-12.
  39. 4607556 Kanda Y, Goodman DS, Canfield RE, Morgan FJ: The amino acid sequence of human plasma prealbumin. J Biol Chem. 1974 Nov 10;249(21):6796-805.
  40. 6093805 Mita S, Maeda S, Shimada K, Araki S: Cloning and sequence analysis of cDNA for human prealbumin. Biochem Biophys Res Commun. 1984 Oct 30;124(2):558-64.
  41. 6300852 Pras M, Prelli F, Franklin EC, Frangione B: Primary structure of an amyloid prealbumin variant in familial polyneuropathy of Jewish origin. Proc Natl Acad Sci U S A. 1983 Jan;80(2):539-42.
  42. 6487335 Nakazato M, Kangawa K, Minamino N, Tawara S, Matsuo H, Araki S: Revised analysis of amino acid replacement in a prealbumin variant (SKO-III) associated with familial amyloidotic polyneuropathy of Jewish origin. Biochem Biophys Res Commun. 1984 Sep 28;123(3):921-8.
  43. 6583672 Dwulet FE, Benson MD: Primary structure of an amyloid prealbumin and its plasma precursor in a heredofamilial polyneuropathy of Swedish origin. Proc Natl Acad Sci U S A. 1984 Feb;81(3):694-8.
  44. 6651852 Tawara S, Nakazato M, Kangawa K, Matsuo H, Araki S: Identification of amyloid prealbumin variant in familial amyloidotic polyneuropathy (Japanese type). Biochem Biophys Res Commun. 1983 Nov 15;116(3):880-8.
  45. 671542 Blake CC, Geisow MJ, Oatley SJ, Rerat B, Rerat C: Structure of prealbumin: secondary, tertiary and quaternary interactions determined by Fourier refinement at 1.8 A. J Mol Biol. 1978 May 25;121(3):339-56.
  46. 7474944 Gustavsson A, Jahr H, Tobiassen R, Jacobson DR, Sletten K, Westermark P: Amyloid fibril composition and transthyretin gene structure in senile systemic amyloidosis. Lab Invest. 1995 Nov;73(5):703-8.
  47. 7599630 Saraiva MJ: Transthyretin mutations in health and disease. Hum Mutat. 1995;5(3):191-6.
  48. 7754382 Monaco HL, Rizzi M, Coda A: Structure of a complex of two plasma proteins: transthyretin and retinol-binding protein. Science. 1995 May 19;268(5213):1039-41.
  49. 7850982 Booth DR, Tan SY, Hawkins PN, Pepys MB, Frustaci A: A novel variant of transthyretin, 59Thr-->Lys, associated with autosomal dominant cardiac amyloidosis in an Italian family. Circulation. 1995 Feb 15;91(4):962-7.
  50. 7910950 Yamamoto K, Hsu SP, Yoshida K, Ikeda S, Nakazato M, Shiomi K, Cheng SY, Furihata K, Ueno I, Yanagisawa N: Familial amyloid polyneuropathy in Taiwan: identification of transthyretin variant (Leu55-->Pro). Muscle Nerve. 1994 Jun;17(6):637-41.
  51. 7914929 Uemichi T, Gertz MA, Benson MD: Amyloid polyneuropathy in two German-American families: a new transthyretin variant (Val 107). J Med Genet. 1994 May;31(5):416-7.
  52. 7923855 Skare J, Jones LA, Myles N, Kane K, Milunsky A, Cohen A, Skinner M: Two transthyretin mutations (glu42gly, his90asn) in an Italian family with amyloidosis. Clin Genet. 1994 Jun;45(6):281-4.
  53. 8019560 Jacobson DR, Buxbaum JN: A double-variant transthyretin allele (Ser 6, Ile 33) in the Israeli patient "SKO" with familial amyloidotic polyneuropathy. Hum Mutat. 1994;3(3):254-60.
  54. 8038017 Hesse A, Altland K, Linke RP, Almeida MR, Saraiva MJ, Steinmetz A, Maisch B: Cardiac amyloidosis: a review and report of a new transthyretin (prealbumin) variant. Br Heart J. 1993 Aug;70(2):111-5.
  55. 8081397 Jacobson DR, Gertz MA, Buxbaum JN: Transthyretin VAL107, a new variant associated with familial cardiac and neuropathic amyloidosis. Hum Mutat. 1994;3(4):399-401.
  56. 8089102 Berni R, Malpeli G, Folli C, Murrell JR, Liepnieks JJ, Benson MD: The Ile-84-->Ser amino acid substitution in transthyretin interferes with the interaction with plasma retinol-binding protein. J Biol Chem. 1994 Sep 23;269(38):23395-8.
  57. 8095302 Benson MD 2nd, Turpin JC, Lucotte G, Zeldenrust S, LeChevalier B, Benson MD: A transthyretin variant (alanine 71) associated with familial amyloidotic polyneuropathy in a French family. J Med Genet. 1993 Feb;30(2):120-2.
  58. 8133316 Yasuda T, Sobue G, Doyu M, Nakazato M, Shiomi K, Yanagi T, Mitsuma T: Familial amyloidotic polyneuropathy with late-onset and well-preserved autonomic function: a Japanese kindred with novel mutant transthyretin (Ala97 to Gly). J Neurol Sci. 1994 Jan;121(1):97-102.
  59. 8257997 Almeida Mdo R, Lopez-Andreu F, Munar-Ques M, Costa PP, Saraiva MJ: Transthyretin ALA 71: a new transthyretin variant in a Spanish family with familial amyloidotic polyneuropathy. Hum Mutat. 1993;2(5):420-1.
  60. 8309582 Murakami T, Tachibana S, Endo Y, Kawai R, Hara M, Tanase S, Ando M: Familial carpal tunnel syndrome due to amyloidogenic transthyretin His 114 variant. Neurology. 1994 Feb;44(2):315-8.
  61. 8352764 Shiomi K, Nakazato M, Matsukura S, Ohnishi A, Hatanaka H, Tsuji S, Murai Y, Kojima M, Kangawa K, Matsuo H: A basic transthyretin variant (Glu61-->Lys) causes familial amyloidotic polyneuropathy: protein and DNA sequencing and PCR-induced mutation restriction analysis. Biochem Biophys Res Commun. 1993 Aug 16;194(3):1090-6.
  62. 8382610 Terry CJ, Damas AM, Oliveira P, Saraiva MJ, Alves IL, Costa PP, Matias PM, Sakaki Y, Blake CC: Structure of Met30 variant of transthyretin and its amyloidogenic implications. EMBO J. 1993 Feb;12(2):735-41.
  63. 8428915 Hamilton JA, Steinrauf LK, Braden BC, Liepnieks J, Benson MD, Holmgren G, Sandgren O, Steen L: The x-ray crystal structure refinements of normal human transthyretin and the amyloidogenic Val-30-->Met variant to 1.7-A resolution. J Biol Chem. 1993 Feb 5;268(4):2416-24.
  64. 8579098 Vidal R, Garzuly F, Budka H, Lalowski M, Linke RP, Brittig F, Frangione B, Wisniewski T: Meningocerebrovascular amyloidosis associated with a novel transthyretin mis-sense mutation at codon 18 (TTRD 18G) Am J Pathol. 1996 Feb;148(2):361-6.
  65. 8990019 Jacobson DR, Pan T, Kyle RA, Buxbaum JN: Transthyretin ILE20, a new variant associated with late-onset cardiac amyloidosis. Hum Mutat. 1997;9(1):83-5.
  66. 9789022 Peterson SA, Klabunde T, Lashuel HA, Purkey H, Sacchettini JC, Kelly JW: Inhibiting transthyretin conformational changes that lead to amyloid fibril formation. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):12956-60.
  67. 9818054 Schormann N, Murrell JR, Benson MD: Tertiary structures of amyloidogenic and non-amyloidogenic transthyretin variants: new model for amyloid fibril formation. Amyloid. 1998 Sep;5(3):175-87.
Target 3 Drug References
  1. Miller SR, Sekijima Y, Kelly JW: Native state stabilization by NSAIDs inhibits transthyretin amyloidogenesis from the most common familial disease variants. Lab Invest. 2004 May;84(5):545-52. [PubMed Link Image]
  2. Almeida MR, Macedo B, Cardoso I, Alves I, Valencia G, Arsequell G, Planas A, Saraiva MJ: Selective binding to transthyretin and tetramer stabilization in serum from patients with familial amyloidotic polyneuropathy by an iodinated diflunisal derivative. Biochem J. 2004 Jul 15;381(Pt 2):351-6. [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.