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Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:04:14
Primary Accession Number DB00468
Secondary Accession Number
  • APRD00563
Name Quinine
Drug Type
  • Approved
  • Small Molecule
Description An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [PubChem]
Synonyms
  1. 6'-Methoxycinchonidine
  2. 6'-Methoxycinchonine
  3. Quinine sulfate
  4. Quinine, Anhydrous
  5. Quinineanhydrous
  6. Quinoline Alkaloid
Brand Names
  1. Aflukin
  2. Chinin
  3. Chinine
  4. Coco-Quinine
  5. None
  6. Quinine Dab
Brand Mixtures
  1. Holis 12 Pr (Aloe + Citrullus Colocynthis + Gamboge + Podophyllum + Quinine + White Hellebore Root)
  2. Holis 21 (Castanea Vesca + Citrullus Colocynthis + Ipecac + Nitric Acid + Quinine + Silver Nitrate)
  3. Holis 22 (Carbon Disulfide + Chenopodium Ambrosioides + Quinine Sulfate + Tobacco)
  4. Holis 73 (Asafetida + Charcoal Activated + Gratiola Officinalis + Lycopodium Clavatum + Magnesium Carbonate + Potassium Carbonate + Quinine + Silver Nitrate)
  5. Holis 78 (Aconitinum + Cedron + Citrullus Colocynthis + Hypericum Perforatum + Plantago Major + Quinine + Quinine Sulfate)
  6. Holis 82 (Acetic Acid + Asafetida + Charcoal Activated + Magnesium Carbonate + Potassium Carbonate + Quinine + Radish + Silver Nitrate)
  7. Salzmann Product M-1 Malena (Potassium Nitrate + Potassium Phosphate Dibasic + Quinine Sulfate + Sodium Chloride + Sodium Sulfate + Sodium Sulfite)
  8. Thc Complex #57 (Arnica Montana + Barium Carbonate + Belladonna + Carbon Disulfide + Cinchona Officinalis + Cocculus Indicus + Conium Maculatum + Ferrum Phosphoricum + Gelsemium Sempervirens + German Chamomile + Hahnemann's Causticum + Lycopodium Clavatum + Oyster Shells + Phosphorus + Pomegranate Bark + Quinine Sulfate + Salicylic Acid + Sanguinaria Canadensis + Sulfur)
  9. Triogene for (Calcium Glycerophosphate + Gentiana Lutea + Iron + Kola + Quinine)
Chemical IUPAC Name (R)-[(5R,7S)-5-ethenyl-1-azabicyclo[2.2.2]octan-7-yl]-(6-methoxyquinolin-4-yl)methanol
Chemical Formula C20H24N2O2
Chemical Structure Structure
CAS Registry Number 130-95-0
InChI Identifier InChI=1/C20H24N2O2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3/t13-,14?,19-,20+/m0/s1
InChI Key LOUPRKONTZGTKE-VOMFEXJBBI
KEGG Drug Not Available
KEGG Compound C06526 Link Image
PubChem Compound 8549 Link Image
PubChem Substance 151706 Link Image
ChEBI ID 15854 Link Image
PharmGKB ID PA451213 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02254522 Link Image
RxList Link http://www.rxlist.com/cgi/generic3/quinine.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Quinine Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Woodward, Doering, J. Am. Chem. Soc. 66, 849 (1944); 67, 860 (1945)
Average Molecular Weight 324.4168
Monoisotopic Molecular Weight 324.1838
State Solid
Melting Point 57 oC
Experimental Water Solubility 500 mg/L Source: PhysProp
Predicted Water Solubility 3.34e-01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 2.6 Source: PhysProp
Predicted LogP 2.82 Calculated using ALOGPS
Experimental LogS -2.76 [ADME Research, USCD]
Predicted LogS -2.99 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 COC1=CC2=C(C=CN=C2C=C1)[C@@H](O)[C@@H]1C[C@H]2CC[N@@]1C[C@@H]2C=C
Canonical SMILES COC1=CC2=C(C=CN=C2C=C1)C(O)C1CC2CCN1CC2C=C
Drug Category
  • Analgesics, Non-Narcotic
  • Antimalarials
  • Muscle Relaxants, Central
ATC Codes
AHFS Codes
  • 08:30.08
  • 92:02.00*
Indication For the treatment of malaria and leg cramps
Pharmacology Quinine is used parenterally to treat life-threatening infections caused by chloroquine-resistant Plasmodium falciparum malaria. Quinine acts as a blood schizonticide although it also has gametocytocidal activity against P. vivax and P. malariae. Because it is a weak base, it is concentrated in the food vacuoles of P. falciparum. It is thought to act by inhibiting heme polymerase, thereby allowing accumulation of its cytotoxic substrate, heme. As a schizonticidal drug, it is less effective and more toxic than chloroquine. However, it has a special place in the management of severe falciparum malaria in areas with known resistance to chloroquine.
Mechanism of Action The theorized mechanism of action for quinine and related anti-malarial drugs is that these drugs are toxic to the malaria parasite. Specifically, the drugs interfere with the parasite's ability to break down and digest hemoglobin. Consequently, the parasite starves and/or builds up toxic levels of partially degraded hemoglobin in itself.
Absorption 76 - 88%
Toxicity Not Available
Protein Binding Approximately 70%
Biotransformation Hepatic, over 80% metabolized by the liver.
Half Life Approximately 18 hours
Dosage Forms
Form Route
Capsule Oral
Liquid Oral
Solution / drops Oral
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol Quinine/quinidine increases the anticoagulant effect
Anisindione Quinine/quinidine increases the anticoagulant effect
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atomoxetine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Atracurium The quinine derivative increases the effect of the muscle relaxant
Dicumarol Quinine/quinidine increases the anticoagulant effect
Digitoxin Quinine/quinidine increases the effect of digoxin
Digoxin Quinine/quinidine increases the effect of digoxin
Gallamine Triethiodide The quinine derivative increases the effect of the muscle relaxant
Mesoridazine Increased risk of cardiotoxicity and arrhythmias
Metocurine The quinine derivative increases the effect of the muscle relaxant
Pancuronium The quinine derivative increases the effect of the muscle relaxant
Succinylcholine The quinine derivative increases the effect of the muscle relaxant
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Thioridazine Increased risk of cardiotoxicity and arrhythmias
Vecuronium The quinine derivative increases the effect of the muscle relaxant
Warfarin Quinine/quinidine increases the anticoagulant effect
Food Interactions
  • Take with food to reduce irritation.
Pathways Not Available
General References
  1. Paintaud G, Alvan G, Berninger E, Gustafsson LL, Idrizbegovic E, Karlsson KK, Wakelkamp M: The concentration-effect relationship of quinine-induced hearing impairment. Clin Pharmacol Ther. 1994 Mar;55(3):317-23. [PubMed Link Image]
  2. Drugs.com Link Image
  3. Wikipedia Link Image
  4. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 3A5 (CYP3A5)
  2. Cytochrome P450 3A4 (CYP3A4)
  3. Cytochrome P450 2D6 (CYP2D6)
  4. Cytochrome P450 1A1 (CYP1A1)
Targets
  1. Hemoglobin subunit alpha
  2. Intermediate conductance calcium-activated potassium channel protein 4
  3. Platelet glycoprotein IX
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 3A5 (CYP3A5)
Enzyme 1 Gene Name CYP3A5
Enzyme 1 SwissProt ID P20815 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P20815|CP3A5_HUMAN Cytochrome P450 3A5 
MDLIPNLAVETWLLLAVSLVLLYLYGTRTHGLFKRLGIPGPTPLPLLGNVLSYRQGLWKF
DTECYKKYGKMWGTYEGQLPVLAITDPDVIRTVLVKECYSVFTNRRSLGPVGFMKSAISL
AEDEEWKRIRSLLSPTFTSGKLKEMFPIIAQYGDVLVRNLRREAEKGKPVTLKDIFGAYS
MDVITGTSFGVNIDSLNNPQDPFVESTKKFLKFGFLDPLFLSIILFPFLTPVFEALNVSL
FPKDTINFLSKSVNRMKKSRLNDKQKHRLDFLQLMIDSQNSKETESHKALSDLELAAQSI
IFIFAGYETTSSVLSFTLYELATHPDVQQKLQKEIDAVLPNKAPPTYDAVVQMEYLDMVV
NETLRLFPVAIRLERTCKKDVEINGVFIPKGSMVVIPTYALHHDPKYWTEPEEFRPERFS
KKKDSIDPYIYTPFGTGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLDTQG
LLQPEKPIVLKVDSRDGTLSGE
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 2 Gene Name CYP3A4
Enzyme 2 SwissProt ID P08684 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Phase 1 Metabolizing Enzyme 3 [top]
Enzyme 3 Name Cytochrome P450 2D6 (CYP2D6)
Enzyme 3 Gene Name CYP2D6
Enzyme 3 SwissProt ID P10635 Link Image
Enzyme 3 SNPs SNPJam Report Link Image
Enzyme 3 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 4 [top]
Enzyme 4 Name Cytochrome P450 1A1 (CYP1A1)
Enzyme 4 Gene Name CYP1A1
Enzyme 4 SwissProt ID P04798 Link Image
Enzyme 4 SNPs SNPJam Report Link Image
Enzyme 4 Protein Sequence >sp|P04798|CP1A1_HUMAN Cytochrome P450 1A1 (EC 1.14.14.1) 
MLFPISMSATEFLLASVIFCLVFWVIRASRPQVPKGLKNPPGPWGWPLIGHMLTLGKNPH
LALSRMSQQYGDVLQIRIGSTPVVVLSGLDTIRQALVRQGDDFKGRPDLYTFTLISNGQS
MSFSPDSGPVWAARRRLAQNGLKSFSIASDPASSTSCYLEEHVSKEAEVLISTLQELMAG
PGHFNPYRYVVVSVTNVICAICFGRRYDHNHQELLSLVNLNNNFGEVVGSGNPADFIPIL
RYLPNPSLNAFKDLNEKFYSFMQKMVKEHYKTFEKGHIRDITDSLIEHCQEKQLDENANV
QLSDEKIINIVLDLFGAGFDTVTTAISWSLMYLVMNPRVQRKIQEELDTVIGRSRRPRLS
DRSHLPYMEAFILETFRHSSFVPFTIPHSTTRDTSLKGFYIPKGRCVFVNQWQINHDQKL
WVNPSEFLPERFLTPDGAIDKVLSEKVIIFGMGKRKCIGETIARWEVFLFLAILLQRVEF
SVPLGVKVDMTPIYGLTMKHACCEHFQMQLRS
Drug Target 1 [top]
Target 1 ID 144
Target 1 Name Hemoglobin subunit alpha
Target 1 Synonyms
  1. Alpha-globin
  2. Hemoglobin alpha chain
Target 1 Gene Name HBA1
Target 1 Protein Sequence >Hemoglobin subunit alpha 
VLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHGK
KVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPA
VHASLDKFLASVSTVLTSKYR
Target 1 Number of Residues 143
Target 1 Molecular Weight 15126
Target 1 Theoretical pI 9.09
Target 1 GO Classification
Function
tetrapyrrole binding
heme binding
binding
oxygen binding
Process
physiological process
cellular physiological process
transport
gas transport
oxygen transport
Component
protein complex
hemoglobin complex
Target 1 General Function Involved in iron ion binding
Target 1 Specific Function Involved in oxygen transport from the lung to the various peripheral tissues
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 386764 Link Image
Target 1 UniProtKB/Swiss-Prot ID P69905 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name HBA_HUMAN Link Image
Target 1 PDB ID 1Y01 Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location Not Available
Target 1 Gene Sequence >429 bp 
ATGGTGCTGTCTCCTGCCGACAAGACCAACGTCAAGGCCGCCTGGGGTAAGGTCGGCGCG
CACGCTGGCGAGTATGGTGCGGAGGCCCTGGAGAGGATGTTCCTGTCCTTCCCCACCACC
AAGACCTACTTCCCGCACTTCGACCTGAGCCACGGCTCTGCCCAGGTTAAGGGCCACGGC
AAGAAGGTGGCCGACGCCCTGACCAACGCCGTGGCGCACGTGGACGACATGCCCAACGCG
CTGTCCGCCCTGAGCGACCTGCACGCGCACAAGCTTCGGGTGGACCCGGTCAACTTCAAG
CTCCTAAGCCACTGCCTGCTGGTGACCCTGGCCGCCCACCTCCCCGCCGAGTTCACCCCT
GCGGTGCACGCCTCCCTGGACAAGTTCCTGGCTTCTGTGAGCACCGTGCTGACCTCCAAA
TACCGTTAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID HBA1 Link Image
Target 1 GenAtlas ID HBA1 Link Image
Target 1 HGNC ID HGNC:4823 Link Image
Target 1 Chromosome Location 16
Target 1 Locus 16p13.3
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Daniels RJ, Peden JF, Lloyd C, Horsley SW, Clark K, Tufarelli C, Kearney L, Buckle VJ, Doggett NA, Flint J, Higgs DR: Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16. Hum Mol Genet. 2001 Feb 15;10(4):339-52. [PubMed Link Image]
  2. Brimhall B, Jones RT, Schneider RG, Hosty TS, Tomlin G, Atkins R: Two new hemoglobins. Hemoglobin Alabama (beta39(C5)Gln leads to Lys) and hemoglobin Montgomery (alpha 48(CD 6) Leu leads to Arg). Biochim Biophys Acta. 1975 Jan 30;379(1):28-32. [PubMed Link Image]
  3. Zhao Y, Zhong M, Liu Z, Xu X: [Rapid detection of the common alpha-thalassemia-2 determinants by PCR assay] Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2001 Jun;18(3):216-8. [PubMed Link Image]
  4. Zhao Y, Xu X: Alpha2(CD31 AGG-->AAG, Arg-->Lys) causing non-deletional alpha-thalassemia in a Chinese family with HbH disease. Haematologica. 2001 May;86(5):541-2. [PubMed Link Image]
  5. Fermi G: Three-dimensional fourier synthesis of human deoxyhaemoglobin at 2-5 A resolution: refinement of the atomic model. J Mol Biol. 1975 Sep 15;97(2):237-56. [PubMed Link Image]
  6. 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]
  7. Abbes S, M'Rad A, Fitzgerald PA, Dormer P, Blouquit Y, Kister J, Galacteros F, Wajcman H: HB Al-Ain Abu Dhabi [alpha 18(A16)Gly----Asp]: a new hemoglobin variant discovered in an Emiratee family. Hemoglobin. 1992;16(5):355-62. [PubMed Link Image]
  8. Fujisawa K, Hattori Y, Ohba Y, Ando S: Hb Yuda or alpha 130(H13)Ala----Asp; a new alpha chain variant with low oxygen affinity. Hemoglobin. 1992;16(5):435-9. [PubMed Link Image]
  9. Wajcman H, Blouquit Y, Vasseur C, Le Querrec A, Laniece M, Melevendi C, Rasore A, Galacteros F: Two new human hemoglobin variants caused by unusual mutational events: Hb Zaire contains a five residue repetition within the alpha-chain and Hb Duino has two residues substituted in the beta-chain. Hum Genet. 1992 Aug;89(6):676-80. [PubMed Link Image]
  10. Silva MM, Rogers PH, Arnone A: A third quaternary structure of human hemoglobin A at 1.7-A resolution. J Biol Chem. 1992 Aug 25;267(24):17248-56. [PubMed Link Image]
  11. 1618774 Vasseur C, Blouquit Y, Kister J, Prome D, Kavanaugh JS, Rogers PH, Guillemin C, Arnone A, Galacteros F, Poyart C, et al.: Hemoglobin Thionville. An alpha-chain variant with a substitution of a glutamate for valine at NA-1 and having an acetylated methionine NH2 terminus. J Biol Chem. 1992 Jun 25;267(18):12682-91.
  12. 1634355 Miyashita H, Hashimoto K, Mohri H, Ohokubo T, Harano T, Harano K, Imai K: Hb Kanagawa [alpha 40(C5)Lys----Met]: a new alpha chain variant with an increased oxygen affinity. Hemoglobin. 1992;16(1-2):1-10.
  13. 1634357 Langdown JV, Davidson RJ, Williamson D: A new alpha chain variant, Hb Turriff [alpha 99(G6)Lys----Glu]: the interference of abnormal hemoglobins in Hb A1c determination. Hemoglobin. 1992;16(1-2):11-7.
  14. 1634363 Orisaka M, Tajima T, Harano T, Harano K, Kushida Y, Imai K: A new alpha chain variant, Hb Hanamaki or alpha 2(139)(HC1)Lys----Glu beta 2, found in a Japanese family. Hemoglobin. 1992;16(1-2):67-71.
  15. 1686260 Jiang NH, Liang S, Wen XJ, Liang R, Su C, Tang Z: Hb Westmead: an alpha 2-globin gene mutation detected by polymerase chain reaction and Stu I cleavage. Hemoglobin. 1991;15(4):291-5.
  16. 1802882 Zwerdling T, Williams S, Nasr SA, Rucknagel DL: Hb Port Huron [alpha 56 (E5)Lys----ARG]: a new alpha chain variant. Hemoglobin. 1991;15(5):381-91.
  17. 2079430 Harkness M, Harkness DR, Kutlar F, Kutlar A, Wilson JB, Webber BB, Codrington JF, Huisman TH: Hb Sun Prairie or alpha(2)130(H13)Ala----Pro beta 2, a new unstable variant occurring in low quantities. Hemoglobin. 1990;14(5):479-89.
  18. 2101836 Wilson JB, Webber BB, Plaseska D, de Alarcon PA, McMillan SK, Huisman TH: Hb Davenport or alpha 2(78)(EF7)Asn----His beta 2. Hemoglobin. 1990;14(6):599-605.
  19. 2606724 Wilson JB, Webber BB, Kutlar A, Reese AL, McKie VC, Lutcher CL, Felice AE, Huisman TH: Hb Evans or alpha 262(E11)Val----Met beta 2; an unstable hemoglobin causing a mild hemolytic anemia. Hemoglobin. 1989;13(6):557-66.
  20. 2752146 Cash FE, Monplaisir N, Goossens M, Liebhaber SA: Locus assignment of two alpha-globin structural mutants from the Caribbean basin: alpha Fort de France (alpha 45 Arg) and alpha Spanish Town (alpha 27 Val). Blood. 1989 Aug 1;74(2):833-5.
  21. 3654264 Fleming PJ, Sumner DR, Wyatt K, Hughes WG, Melrose WD, Jupe DM, Baikie MJ: Hemoglobin Hobart or alpha 20(Bl)His----Arg: a new alpha chain hemoglobin variant. Hemoglobin. 1987;11(3):211-20.
  22. 3754246 Como PF, Barber S, Sage RE, Trent RJ, Kronenberg H: Hemoglobin Woodville: alpha (2)6(A4) aspartic acid----tyrosine. Hemoglobin. 1986;10(2):135-41.
  23. 4212045 Reed RE, Winter WP, Rucknagel DL: Haemoglobin inkster (alpha2 85aspartic acid leads to valine beta2) coexisting with beta-thalassaemia in a Caucasian family. Br J Haematol. 1974 Mar;26(3):475-84.
  24. 4528583 Huisman TH, Wilson JB, Gravely M, Hubbard M: Hemoglobin Grady: the first example of a variant with elongated chains due to an insertion of residues. Proc Natl Acad Sci U S A. 1974 Aug;71(8):3270-3.
  25. 4744335 Sumida I, Ota Y, Imamura T, Yanase T: Hemoglobin Sawara: alpha 6(A4) aspartic acid leads to alanine. Biochim Biophys Acta. 1973 Sep 21;322(1):23-6.
  26. 478977 Sanguansermsri T, Matragoon S, Changloah L, Flatz G: Hemoglobin Suan-Dok (alpha 2 109 (G16) Leu replaced by Arg beta 2): an unstable variant associated with alpha-thalassemia. Hemoglobin. 1979;3(2-3):161-74.
  27. 5115619 Fujiwara N, Maekawa T, Matsuda G: Hemoglobin Atago (alpha2-85Tyr beta-2) a new abnormal human hemoglobin found in Nagasaki. Biochemical studies on hemoglobins and myoglobins. VI. Int J Protein Res. 1971;3(1):35-9.
  28. 5780195 Charache S, Mondzac AM, Gessner U: Hemoglobin Hasharon (alpha-2-47 his(CD5)beta-2): a hemoglobin found in low concentration. J Clin Invest. 1969 May;48(5):834-47.
  29. 6244294 Wilson JT, Wilson LB, Reddy VB, Cavallesco C, Ghosh PK, deRiel JK, Forget BG, Weissman SM: Nucleotide sequence of the coding portion of human alpha globin messenger RNA. J Biol Chem. 1980 Apr 10;255(7):2807-15.
  30. 6452630 Liebhaber SA, Goossens MJ, Kan YW: Cloning and complete nucleotide sequence of human 5'-alpha-globin gene. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7054-8.
  31. 6526652 Zeng YT, Huang SZ, Qiu XK, Cheng GC, Ren ZR, Jin QC, Chen CY, Jiao CT, Tang ZG, Liu RH, et al.: Hemoglobin Chongqing [alpha 2(NA2)Leu----Arg] and hemoglobin Harbin [alpha 16(A14)Lys----Met] found in China. Hemoglobin. 1984;8(6):569-81.
  32. 6815131 Harano T, Harano K, Shibata S, Ueda S, Imai K, Seki M: HB Handa [alpha 90 (FG 2) Lys replaced by Met]: structure and biosynthesis of a new slightly higher oxygen affinity variant. Hemoglobin. 1982;6(4):379-89.
  33. 7161109 Zeng YT, Huang SZ, Zhou XD, Qiu XK, Dong QY, Li MY, Bai JH: Hb Shenyang (alpha 26 (B7) Ala replaced by Glu): a new unstable variant found in China. Hemoglobin. 1982;6(6):625-8.
  34. 7448866 Michelson AM, Orkin SH: The 3' untranslated regions of the duplicated human alpha-globin genes are unexpectedly divergent. Cell. 1980 Nov;22(2 Pt 2):371-7.
  35. 7470621 Honig GR, Shamsuddin M, Zaizov R, Steinherz M, Solar I, Kirschmann C: Hemoglobin Petah Tikva (alpha 110 ala replaced by asp): a new unstable variant with alpha-thalassemia-like expression. Blood. 1981 Apr;57(4):705-11.
  36. 7558876 Harano T, Harano K, Imai K, Murakami T, Matsubara H: Hb Kurosaki [alpha 7(A5)Lys-->Glu]: a new alpha chain variant found in a Japanese woman. Hemoglobin. 1995 May-Jul;19(3-4):197-201.
  37. 7713747 Yalcin A, Avcu F, Beyan C, Gurgey A, Ural AU: A case of HB J-Meerut (or Hb J-Birmingham) [alpha 120(H3)Ala-->Glu] Hemoglobin. 1994 Nov;18(6):433-5.
  38. 7786798 Darbellay R, Mach-Pascual S, Rose K, Graf J, Beris P: Haemoglobin Tunis-Bizerte: a new alpha 1 globin 129 Leu-->Pro unstable variant with thalassaemic phenotype. Br J Haematol. 1995 May;90(1):71-6.
  39. 8195005 Giordano PC, Harteveld CL, Streng H, Oosterwijk JC, Heister JG, Amons R, Bernini LF: Hb Kurdistan [alpha 47(CE5)Asp-->Tyr], a new alpha chain variant in combination with beta (0)-thalassemia. Hemoglobin. 1994 Jan;18(1):11-8.
  40. 8294199 Wajcman H, Kalmes G, Groff P, Prome D, Riou J, Galacteros F: Hb Melusine [alpha 114(GH2)Pro-->Ser]: a new neutral hemoglobin variant. Hemoglobin. 1993 Oct;17(5):397-405.
  41. 8294200 Wajcman H, Kister J, M'Rad A, Marden MC, Riou J, Galacteros F: Hb Val de Marne [alpha 133(H16)Ser-->Arg]: a new hemoglobin variant with moderate increase in oxygen affinity. Hemoglobin. 1993 Oct;17(5):407-17.
  42. 8448109 Kavanaugh JS, Moo-Penn WF, Arnone A: Accommodation of insertions in helices: the mutation in hemoglobin Catonsville (Pro 37 alpha-Glu-Thr 38 alpha) generates a 3(10)-->alpha bulge. Biochemistry. 1993 Mar 16;32(10):2509-13.
  43. 8745434 Harano T, Harano K, Imai K, Terunuma S: HB Swan River [alpha 6(A4)ASP-->Gly] observed in a Japanese man. Hemoglobin. 1996 Feb;20(1):75-8.
  44. 9322075 Brennan SO, Matthews JR: Hb Auckland [alpha 87(F8) His-->Asn]: a new mutation of the proximal histidine identified by electrospray mass spectrometry. Hemoglobin. 1997 Sep;21(5):393-403.
  45. 9452028 Wajcman H, Prehu MO, Prehu C, Blouquit Y, Prome D, Galacteros F: Hemoglobin Phnom Penh [alpha117Phe(H1)-Ile-alpha118Thr(H2)]; evidence for a hotspot for insertion of residues in the third exon of the alpha1-globin gene. Hum Mutat. 1998;Suppl 1:S20-2.
  46. 9494044 Wajcman H, Kister J, Riou J, Galacteros F, Girot R, Maier-Redelsperger M, Nayudu NV, Giordano PC: Hb Godavari [alpha 95(G2)Pro-->Thr]: a neutral amino acid substitution in the alpha 1 beta 2 interface that modifies the electrophoretic mobility of hemoglobin. Hemoglobin. 1998 Jan;22(1):11-22.
  47. 9665850 Sutherland-Smith AJ, Baker HM, Hofmann OM, Brittain T, Baker EN: Crystal structure of a human embryonic haemoglobin: the carbonmonoxy form of gower II (alpha2 epsilon2) haemoglobin at 2.9 A resolution. J Mol Biol. 1998 Jul 17;280(3):475-84.
Target 1 Drug References
  1. 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. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 462
Target 2 Name Intermediate conductance calcium-activated potassium channel protein 4
Target 2 Synonyms
  1. IK1
  2. IKCa1
  3. KCa4
  4. Putative Gardos channel
  5. SK4
Target 2 Gene Name KCNN4
Target 2 Protein Sequence >Intermediate conductance calcium-activated potassium channel protein 4 
MGGDLVLGLGALRRRKRLLEQEKSLAGWALVLAGTGIGLMVLHAEMLWFGGCSWALYLFL
VKCTISISTFLLLCLIVAFHAKEVQLFMTDNGLRDWRVALTGRQAAQIVLELVVCGLHPA
PVRGPPCVQDLGAPLTSPQPWPGFLGQGEALLSLAMLLRLYLVPRAVLLRSGVLLNASYR
SIGALNQVRFRHWFVAKLYMNTHPGRLLLGLTLGLWLTTAWVLSVAERQAVNATGHLSDT
LWLIPITFLTIGYGDVVPGTMWGKIVCLCTGVMGVCCTALLVAVVARKLEFNKAEKHVHN
FMMDIQYTKEMKESAARVLQEAWMFYKHTRRKESHAARRHQRKLLAAINAFRQVRLKHRK
LREQVNSMVDISKMHMILYDLQQNLSSSHRALEKQIDTLAGKLDALTELLSTALGPRQLP
EPSQQSK
Target 2 Number of Residues 434
Target 2 Molecular Weight 47696
Target 2 Theoretical pI 10.39
Target 2 GO Classification
Function
voltage-gated ion channel activity
voltage-gated potassium channel activity
transporter activity
ion transporter activity
ion channel activity
cation channel activity
potassium channel activity
calcium-activated potassium channel activity
binding
protein binding
calmodulin binding
Process
physiological process
cellular physiological process
transport
ion transport
cation transport
monovalent inorganic cation transport
potassium ion transport
Component
protein complex
voltage-gated potassium channel complex
cell
membrane
intrinsic to membrane
integral to membrane
Target 2 General Function Inorganic ion transport and metabolism
Target 2 Specific Function Forms a voltage-independent potassium channel that is activated by intracellular calcium. Activation is followed by membrane hyperpolarization which promotes calcium influx. The channel is blocked by clotrimazole and charybdotoxin but is insensitive to apamin
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 29-49
  • 59-79
  • 108-128
  • 143-163
  • 207-227
  • 241-261
  • 265-285
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 2584866 Link Image
Target 2 UniProtKB/Swiss-Prot ID O15554 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name KCNN4_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 2 Gene Sequence >1284 bp 
ATGGGCGGGGATCTGGTGCTTGGCCTGGGGGCCTTGAGACGCCGAAAGCGCTTGCTGGAG
CAGGAGAAGTCTCTGGCCGGCTGGGCACTGGTGCTGGCAGGAACTGGCATTGGACTCATG
GTGCTGCATGCAGAGATGCTGTGGTTCGGGGGGTGCTCGTGGGCGCTCTACCTGTTCCTG
GTTAAATGCACGATCAGCATTTCCACCTTCTTACTCCTCTGCCTCATCGTGGCCTTTCAT
GCCAAAGAGGTCCAGCTGTTCATGACCGACAACGGGCTGCGGGACTGGCGCGTGGCGCTG
ACCGGGCGGCAGGCGGCGCAGATCGTGCTGGAGCTGGTGGTGTGTGGGCTGCACCCGGCG
CCCGTGCGGGGCCCGCCGTGCGTGCAGGATTTAGGGGCGCCGCTGACCTCCCCGCAGCCC
TGGCCGGGATTCCTGGGCCAAGGGGAAGCGCTGCTGTCCCTGGCCATGCTGCTGCGTCTC
TACCTGGTGCCCCGCGCCGTGCTCCTGCGCAGCGGCGTCCTGCTCAACGCTTCCTACCGC
AGCATCGGCGCTCTCAATCAAGTCCGCTTCCGCCACTGGTTCGTGGCCAAGCTTTACATG
AACACGCACCCTGGCCGCCTGCTGCTCGGCCTCACGCTTGGCCTCTGGCTGACCACCGCC
TGGGTGCTGTCCGTGGCCGAGAGGCAGGCTGTTAATGCCACTGGGCACCTTTCAGACACA
CTTTGGCTGATCCCCATCACATTCCTGACCATCGGCTATGGTGACGTGGTGCCGGGCACC
ATGTGGGGCAAGATCGTCTGCCTGTGCACTGGAGTCATGGGTGTCTGCTGCACAGCCCTG
CTGGTGGCCGTGGTGGCCCGGAAGCTGGAGTTTAACAAGGCAGAGAAGCACGTGCACAAC
TTCATGATGGATATCCAGTATACCAAAGAGATGAAGGAGTCCGCTGCCCGAGTGCTACAA
GAAGCCTGGATGTTCTACAAACATACTCGCAGGAAGGAGTCTCATGCTGCCCGCAGGCAT
CAGCGCAAGCTGCTGGCCGCCATCAACGCGTTCCGCCAGGTGCGGCTGAAACACCGGAAG
CTCCGGGAACAAGTGAACTCCATGGTGGACATCTCCAAGATGCACATGATCCTGTATGAC
CTGCAGCAGAATCTGAGCAGCTCACACCGGGCCCTGGAGAAACAGATTGACACGCTGGCG
GGGAAGCTGGATGCCCTGACTGAGCTGCTTAGCACTGCCCTGGGGCCGAGGCAGCTTCCA
GAACCCAGCCAGCAGTCCAAGTAG
Target 2 GenBank Gene ID
Target 2 GeneCard ID KCNN4 Link Image
Target 2 GenAtlas ID KCNN4 Link Image
Target 2 HGNC ID HGNC:6293 Link Image
Target 2 Chromosome Location 19
Target 2 Locus 19q13.2
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Fanger CM, Ghanshani S, Logsdon NJ, Rauer H, Kalman K, Zhou J, Beckingham K, Chandy KG, Cahalan MD, Aiyar J: Calmodulin mediates calcium-dependent activation of the intermediate conductance KCa channel, IKCa1. J Biol Chem. 1999 Feb 26;274(9):5746-54. [PubMed Link Image]
  2. Wulff H, Gutman GA, Cahalan MD, Chandy KG: Delineation of the clotrimazole/TRAM-34 binding site on the intermediate conductance calcium-activated potassium channel, IKCa1. J Biol Chem. 2001 Aug 24;276(34):32040-5. Epub 2001 Jun 25. [PubMed Link Image]
  3. Ishii TM, Silvia C, Hirschberg B, Bond CT, Adelman JP, Maylie J: A human intermediate conductance calcium-activated potassium channel. Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11651-6. [PubMed Link Image]
  4. Joiner WJ, Wang LY, Tang MD, Kaczmarek LK: hSK4, a member of a novel subfamily of calcium-activated potassium channels. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):11013-8. [PubMed Link Image]
  5. Logsdon NJ, Kang J, Togo JA, Christian EP, Aiyar J: A novel gene, hKCa4, encodes the calcium-activated potassium channel in human T lymphocytes. J Biol Chem. 1997 Dec 26;272(52):32723-6. [PubMed Link Image]
  6. Ghanshani S, Coleman M, Gustavsson P, Wu AC, Gargus JJ, Gutman GA, Dahl N, Mohrenweiser H, Chandy KG: Human calcium-activated potassium channel gene KCNN4 maps to chromosome 19q13.2 in the region deleted in diamond-blackfan anemia. Genomics. 1998 Jul 1;51(1):160-1. [PubMed Link Image]
Target 2 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]
Drug Target 3 [top]
Target 3 ID 976
Target 3 Name Platelet glycoprotein IX
Target 3 Synonyms
  1. CD42a antigen
  2. GPIX
  3. Platelet glycoprotein IX precursor
Target 3 Gene Name GP9
Target 3 Protein Sequence >Platelet glycoprotein IX precursor 
MPAWGALFLLWATAEATKDCPSPCTCRALETMGLWVDCRGHGLTALPALPARTRHLLLAN
NSLQSVPPGAFDHLPQLQTLDVTQNPWHCDCSLTYLRLWLEDRTPEALLQVRCASPSLAA
HGPLGRLTGYQLGSCGWQLQASWVRPGVLWDVALVAVAALGLALLAGLLCATTEALD
Target 3 Number of Residues 179
Target 3 Molecular Weight 19046
Target 3 Theoretical pI 6.32
Target 3 GO Classification Not Available
Target 3 General Function Involved in blood clotting
Target 3 Specific Function The GPIb-V-IX complex functions as the von Willebrand factor receptor and mediates von willebrand factor-dependent platelet adhesion to blood vessels. The adhesion of platelets to injured vascular surfaces in the arterial circulation is a critical initiating event in hemostasis. GP-IX may provide for membrane insertion and orientation of GP-Ib
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • 1-16
Target 3 Transmembrane Regions
  • 152-171
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 2160046 Link Image
Target 3 UniProtKB/Swiss-Prot ID P14770 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name GPIX_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Membrane
  • single-pass type I membrane protein
Target 3 Gene Sequence >534 bp 
ATGCCTGCCTGGGGAGCCCTGTTCCTGCTCTGGGCCACAGCAGAGGCCACCAAGGACTGC
CCCAGCCCATGTACCTGCCGCGCCCTGGAAACCATGGGGCTGTGGGTGGACTGCAGGGGC
CACGGACTCACGGCCCTGCCTGCCCTGCCGGCCCGCACCCGCCACCTTCTGCTGGCCAAC
AACAGCCTTCAGTCCGTGCCCCCGGGAGCCTTTGACCACCTGCCCCAGCTGCAGACCCTC
GATGTGACGCAGAACCCCTGGCACTGTGACTGCAGCCTCACCTATCTGCGCCTCTGGCTG
GAGGACCGCACGCCCGAGGCCCTGCTGCAGGTCCGCTGTGCCAGCCCCAGCCTCGCTGCC
CATGGCCCGCTGGGCCGGCTGACAGGCTACCAGCTGGGCAGCTGTGGCTGGCAGCTGCAG
GCGTCCTGGGTGCGCCCGGGGGTCTTGTGGGACGTGGCGCTGGTCGCCGTGGCCGCGCTG
GGCCTGGCTCTTCTGGCTGGCCTGCTGTGTGCCACCACAGAGGCCCTGGATTGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID GP9 Link Image
Target 3 GenAtlas ID GP9 Link Image
Target 3 HGNC ID HGNC:4444 Link Image
Target 3 Chromosome Location 3
Target 3 Locus 3q21
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. 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]
  2. Hickey MJ, Deaven LL, Roth GJ: Human platelet glycoprotein IX. Characterization of cDNA and localization of the gene to chromosome 3. FEBS Lett. 1990 Nov 12;274(1-2):189-92. [PubMed Link Image]
  3. Hickey MJ, Williams SA, Roth GJ: Human platelet glycoprotein IX: an adhesive prototype of leucine-rich glycoproteins with flank-center-flank structures. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6773-7. [PubMed Link Image]
  4. Roth GJ, Ozols J, Nugent DJ, Williams SA: Isolation and characterization of human platelet glycoprotein IX. Biochem Biophys Res Commun. 1988 Oct 31;156(2):931-9. [PubMed Link Image]
  5. Hickey MJ, Roth GJ: Characterization of the gene encoding human platelet glycoprotein IX. J Biol Chem. 1993 Feb 15;268(5):3438-43. [PubMed Link Image]
  6. Wright SD, Michaelides K, Johnson DJ, West NC, Tuddenham EG: Double heterozygosity for mutations in the platelet glycoprotein IX gene in three siblings with Bernard-Soulier syndrome. Blood. 1993 May 1;81(9):2339-47. [PubMed Link Image]
  7. Hayashi T, Suzuki K, Yahagi A, Akiba J, Tajima K, Satoh S, Sasaki H: Corrected DNA sequence of the platelet glycoprotein IX gene. Thromb Haemost. 1997 May;77(5):1034-5. [PubMed Link Image]
Target 3 Drug References
  1. Asvadi P, Ahmadi Z, Chong BH: Drug-induced thrombocytopenia: localization of the binding site of GPIX-specific quinine-dependent antibodies. Blood. 2003 Sep 1;102(5):1670-7. Epub 2003 May 8. [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.