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Showing drug card for Indapamide (DB00808)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:03:43
Primary Accession Number DB00808
Secondary Accession Number
  • APRD01031
Name Indapamide
Drug Type
  • Approved
  • Small Molecule
Description A benzamide-sulfonamide-indole. It is called a thiazide-like diuretic but structure is different enough (lacking the thiazo-ring) so it is not clear that the mechanism is comparable. [PubChem]
Synonyms
  1. Indapamida [INN-Spanish]
  2. Indapamidum [INN-Latin]
Brand Names
  1. Apo-Indapamide
  2. Arifon
  3. Bajaten
  4. Cormil
  5. Damide
  6. Fludex
  7. Gen-Indapamide
  8. Idapamide
  9. Indaflex
  10. Indamol
  11. Ipamix
  12. Lozide
  13. Lozol
  14. Natrilix
  15. Natrix
  16. Noranat
  17. Novo-Indapamide
  18. Nu-Indapamide
  19. Pressurai
  20. Tandix
  21. Tertensif
  22. Veroxil
Brand Mixtures Not Available
Chemical IUPAC Name 4-chloro-N-(2-methyl-2,3-dihydroindol-1-yl)-3-sulfamoylbenzamide
Chemical Formula C16H16ClN3O3S
Chemical Structure Structure
CAS Registry Number 26807-65-8
InChI Identifier InChI=1/C16H16ClN3O3S/c1-10-8-11-4-2-3-5-14(11)20(10)19-16(21)12-6-7-13(17)15(9-12)24(18,22)23/h2-7,9-10H,8H2,1H3,(H,19,21)(H2,18,22,23)/f/h19H,18H2
InChI Key NDDAHWYSQHTHNT-VNHAUOCNCG
KEGG Drug D00345 Link Image
KEGG Compound Not Available
PubChem Compound 3702 Link Image
PubChem Substance 7847411 Link Image
ChEBI ID Not Available
PharmGKB ID PA449975 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02240350 Link Image
RxList Link http://www.rxlist.com/cgi/generic/indap.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/loz1241.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Indapamide Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 365.8350
Monoisotopic Molecular Weight 365.0601
State Solid
Melting Point 161 oC
Experimental Water Solubility 75 mg/L Source: PhysProp
Predicted Water Solubility 3.42e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 2.2 Source: PhysProp
Predicted LogP 2.52 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.03 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 8.8
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 C[C@H]1CC2=CC=CC=C2N1NC(=O)C1=CC(=C(Cl)C=C1)S(N)(=O)=O
Canonical SMILES CC1CC2=CC=CC=C2N1NC(=O)C1=CC(=C(Cl)C=C1)S(N)(=O)=O
Drug Category
  • Antihypertensive Agents
  • Diuretics
ATC Codes
AHFS Codes
  • 40:28.24
Indication For the treatment of hypertension, alone or in combination with other antihypertensive drugs as well as for the treatment of salt and fluid retention associated with congestive heart failure or edema from pregnancy.
Pharmacology Indapamide is an antihypertensive and a diuretic. It contains both a polar sulfamoyl chlorobenzamide moiety and a lipid- soluble methylindoline moiety. Indapamide bears a structural similarity to the triazide diuretics which are known to decrease vascular smooth muscle reactivity. However, it differs chemically from the thiazides in that it does not possess the thiazide ring system and contains only one sulfonamide group. Indapamide appears to cause vasodilation, probably by inhibiting the passage of calcium and other ions (sodium, potassium) across membranes. This same effect may cause hypokalcemia in susceptible individuals. Indapamide has also been shown to cause uterine myometrial relaxation in experimental animals. Overall, indapamide has an extra-renal antihypertensive action resulting in a decrease in vascular hyperreactivity and a reduction in total peripheral and arteriolar resistance.
Mechanism of Action Indapamide blocks the slow component of delayed rectifier potassium current (IKs) without altering the rapid component (IKr) or the inward rectifier current. Specifically it blocks or antagonizes the action the proteins KCNQ1 and KCNE1. Indapamide is also thought to stimulate the synthesis of the vasodilatory hypotensive prostaglandin PGE2.
Absorption Rapidly absorbed from gastrointestinal tract.
Toxicity Side effects include electrolyte imbalance (potassium or salt depletion due to too much fluid loss), nausea, stomach disorders, vomiting, weakness
Protein Binding 71-79%
Biotransformation Primarily hepatic. Indapamide is an extensively metabolized drug with only about 7+ACU- of the total dose administered, recovered in the urine as unchanged drug during the first 48 hours after administration.
Half Life 14 hours (biphasic)
Dosage Forms
Form Route
Tablet Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Not Available
Drug Interactions
Drug Interaction
Amantadine The diuretic increases the adverse effect of amantadine
Deslanoside Possible electrolyte variations and arrhythmias
Diazoxide Significant hyperglycemic effect
Digitoxin Possible electrolyte variations and arrhythmias
Digoxin Possible electrolyte variations and arrhythmias
Dofetilide Increased risk of cardiotoxicity and arrhythmias
Lithium The thiazide diuretic increases serum levels of lithium
Food Interactions
  • Take without regard to meals. Magnesium, potassium and zinc needs increased.
Pathways
Name SMPDB Link KEGG Link
Indapamide Pathway SMP00110 Link Image
General References
  1. Wikipedia Link Image
  2. RxList Link Image
  3. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Potassium voltage-gated channel subfamily E member 1
  2. Potassium voltage-gated channel subfamily KQT member 1
Drug Target 1 [top]
Target 1 ID 544
Target 1 Name Potassium voltage-gated channel subfamily E member 1
Target 1 Synonyms
  1. Delayed rectifier potassium channel subunit IsK
  2. IKs producing slow voltage-gated potassium channel subunit beta Mink
  3. Minimal potassium channel
Target 1 Gene Name KCNE1
Target 1 Protein Sequence >Potassium voltage-gated channel subfamily E member 1
MILSNTTAVTPFLTKLWQETVQQGGNMSGLARRSPRSSDGKLEALYVLMVLGFFGFFTLG
IMLSYIRSKKLEHSNDPFNVYIESDAWQEKDKAYVQARVLESYRSCYVVENHLAIEQPNT
HLPETKPSP
Target 1 Number of Residues 131
Target 1 Molecular Weight 14675
Target 1 Theoretical pI 7.60
Target 1 GO Classification
Function
transporter activity
ion transporter activity
ion channel activity
voltage-gated ion channel activity
voltage-gated potassium channel activity
Process
cation transport
monovalent inorganic cation transport
potassium ion transport
physiological process
cellular physiological process
transport
ion transport
Component
cell
membrane
Target 1 General Function Involved in voltage-gated potassium channel activity
Target 1 Specific Function Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Assembled with KCNQ1/KVLQT1 is proposed to form the slowly activating delayed rectifier cardiac potassium (IKs) channel. The outward current reaches its steady state only after 50 seconds. Assembled with KCNH2/HERG may modulate the rapidly activating component of the delayed rectifying potassium current in heart (IKr)
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 44-66
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 386838 Link Image
Target 1 UniProtKB/Swiss-Prot ID P15382 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name KCNE1_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • single-pass type I membrane protein
Target 1 Gene Sequence >390 bp
ATGATCCTGTCTAACACCACAGCGGTGACGCCCTTTCTGACCAAGCTGTGGCAGGAGACA
GTTCAGCAGGGTGGCAACATGTCGGGCCTGGCCCGCAGGTCCCCCCGCAGCAGTGACGGC
AAGCTGGAGGCCCTCTACGTCCTCATGGTACTGGGATTCTTCGGCTTCTTCACCCTGGGC
ATCATGCTGAGCTACATCCGCTCCAAGAAGCTGGAGCACTCGAACGACCCATTCAACGTC
TACATCGAGTCCGATGCCTGGCAAGAGAAGGACAAGGCCTATGTCCAGGCCCGGGTCCTG
GAGAGCTACAGGTCGTGCTATGTCGTTGAAAACCATCTGGCCATAGAACAACCCAACACA
CACCTTCCTGAGACGAAGCCTTCCCCATGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID KCNE1 Link Image
Target 1 GenAtlas ID KCNE1 Link Image
Target 1 HGNC ID HGNC:6240 Link Image
Target 1 Chromosome Location Not Available
Target 1 Locus Not Available
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Bianchi L, Shen Z, Dennis AT, Priori SG, Napolitano C, Ronchetti E, Bryskin R, Schwartz PJ, Brown AM: Cellular dysfunction of LQT5-minK mutants: abnormalities of IKs, IKr and trafficking in long QT syndrome. Hum Mol Genet. 1999 Aug;8(8):1499-507. [PubMed Link Image]
  2. Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT: Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 Sep 5;102(10):1178-85. [PubMed Link Image]
  3. Schulze-Bahr E, Schwarz M, Hauenschild S, Wedekind H, Funke H, Haverkamp W, Breithardt G, Pongs O, Isbrandt D: A novel long-QT 5 gene mutation in the C-terminus (V109I) is associated with a mild phenotype. J Mol Med. 2001 Sep;79(9):504-9. [PubMed Link Image]
  4. Abbott GW, Goldstein SA: Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism. FASEB J. 2002 Mar;16(3):390-400. [PubMed Link Image]
  5. Murai T, Kakizuka A, Takumi T, Ohkubo H, Nakanishi S: Molecular cloning and sequence analysis of human genomic DNA encoding a novel membrane protein which exhibits a slowly activating potassium channel activity. Biochem Biophys Res Commun. 1989 May 30;161(1):176-81. [PubMed Link Image]
  6. Lai LP, Deng CL, Moss AJ, Kass RS, Liang CS: Polymorphism of the gene encoding a human minimal potassium ion channel (minK). Gene. 1994 Dec 30;151(1-2):339-40. [PubMed Link Image]
  7. Tesson F, Donger C, Denjoy I, Berthet M, Bennaceur M, Petit C, Coumel P, Schwarts K, Guicheney P: Exclusion of KCNE1 (IsK) as a candidate gene for Jervell and Lange-Nielsen syndrome. J Mol Cell Cardiol. 1996 Sep;28(9):2051-5. [PubMed Link Image]
  8. McDonald TV, Yu Z, Ming Z, Palma E, Meyers MB, Wang KW, Goldstein SA, Fishman GI: A minK-HERG complex regulates the cardiac potassium current I(Kr). Nature. 1997 Jul 17;388(6639):289-92. [PubMed Link Image]
  9. Chouabe C, Neyroud N, Guicheney P, Lazdunski M, Romey G, Barhanin J: Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias. EMBO J. 1997 Sep 1;16(17):5472-9. [PubMed Link Image]
  10. Tyson J, Tranebjaerg L, Bellman S, Wren C, Taylor JF, Bathen J, Aslaksen B, Sorland SJ, Lund O, Malcolm S, Pembrey M, Bhattacharya S, Bitner-Glindzicz M: IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome. Hum Mol Genet. 1997 Nov;6(12):2179-85. [PubMed Link Image]
  11. 9354783 Schulze-Bahr E, Wang Q, Wedekind H, Haverkamp W, Chen Q, Sun Y, Rubie C, Hordt M, Towbin JA, Borggrefe M, Assmann G, Qu X, Somberg JC, Breithardt G, Oberti C, Funke H: KCNE1 mutations cause jervell and Lange-Nielsen syndrome. Nat Genet. 1997 Nov;17(3):267-8.
  12. 9354802 Splawski I, Tristani-Firouzi M, Lehmann MH, Sanguinetti MC, Keating MT: Mutations in the hminK gene cause long QT syndrome and suppress IKs function. Nat Genet. 1997 Nov;17(3):338-40.
  13. 9445165 Duggal P, Vesely MR, Wattanasirichaigoon D, Villafane J, Kaushik V, Beggs AH: Mutation of the gene for IsK associated with both Jervell and Lange-Nielsen and Romano-Ward forms of Long-QT syndrome. Circulation. 1998 Jan 20;97(2):142-6.
Target 1 Drug References
  1. Ohya S, Asakura K, Muraki K, Watanabe M, Imaizumi Y: Molecular and functional characterization of ERG, KCNQ, and KCNE subtypes in rat stomach smooth muscle. Am J Physiol Gastrointest Liver Physiol. 2002 Feb;282(2):G277-87. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 741
Target 2 Name Potassium voltage-gated channel subfamily KQT member 1
Target 2 Synonyms
  1. IKs producing slow voltage-gated potassium channel subunit alpha KvLQT1
  2. KQT-like 1
  3. Voltage-gated potassium channel subunit Kv7.1
Target 2 Gene Name KCNQ1
Target 2 Protein Sequence >Potassium voltage-gated channel subfamily KQT member 1
MAAASSPPRAERKRWGWGRLPGARRGSAGLAKKCPFSLELAEGGPAGGALYAPIAPGAPG
PAPPASPAAPAAPPVASDLGPRPPVSLDPRVSIYSTRRPVLARTHVQGRVYNFLERPTGW
KCFVYHFAVFLIVLVCLIFSVLSTIEQYAALATGTLFWMEIVLVVFFGTEYVVRLWSAGC
RSKYVGLWGRLRFARKPISIIDLIVVVASMVVLCVGSKGQVFATSAIRGIRFLQILRMLH
VDRQGGTWRLLGSVVFIHRQELITTLYIGFLGLIFSSYFVYLAEKDAVNESGRVEFGSYA
DALWWGVVTVTTIGYGDKVPQTWVGKTIASCFSVFAISFFALPAGILGSGFALKVQQKQR
QKHFNRQIPAAASLIQTAWRCYAAENPDSSTWKIYIRKAPRSHTLLSPSPKPKKSVVVKK
KKFKLDKDNGVTPGEKMLTVPHITCDPPEERRLDHFSVDGYDSSVRKSPTLLEVSMPHFM
RTNSFAEDLDLEGETLLTPITHISQLREHHRATIKVIRRMQYFVAKKKFQQARKPYDVRD
VIEQYSQGHLNLMVRIKELQRRLDQSIGKPSLFISVSEKSKDRGSNTIGARLNRVEDKVT
QLDQRLALITDMLHQLLSLHGGSTPGSGGPPREGGAHITQPCGSGGSVDPELFLPSNTLP
TYEQLTVPRRGPDEGS
Target 2 Number of Residues 687
Target 2 Molecular Weight 74699
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
Process
cation transport
monovalent inorganic cation transport
potassium ion transport
physiological process
cellular physiological process
transport
ion transport
Component
protein complex
voltage-gated potassium channel complex
cell
membrane
Target 2 General Function Inorganic ion transport and metabolism
Target 2 Specific Function Probably important in cardiac repolarization. Associates with KCNE1 (MinK) to form the I(Ks) cardiac potassium current. Elicits a rapidly activating, potassium-selective outward current. Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current in CHO cells in which cloned KCNQ1/KCNE1 channels were coexpressed with M1 muscarinic receptors. May associate also with KCNE3 (MiRP2) to form the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions, which is reduced in cystic fibrosis and pathologically stimulated in cholera and other forms of secretory diarrhea
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 122-142
  • 148-168
  • 197-217
  • 226-248
  • 262-282
  • 328-348
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 2465531 Link Image
Target 2 UniProtKB/Swiss-Prot ID P51787 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name KCNQ1_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 2 Gene Sequence >2031 bp
ATGGCCGCGGCCTCCTCCCCGCCCAGGGCCGAGAGGAAGCGCTGGGGTTGGGGCCGCCTG
CCAGGCGCCCGGCGGGGCAGCGCGGGCCTGGCCAAGAAGTGCCCCTTCTCGCTGGAGCTG
GCGGAGGGCGGCCCGGCGGGCGGCGCGCTCTACGCGCCCATCGCGCCCGGCGCCCCAGGT
CCCGCGCCCCCTGCGTCCCCGGCCGCGCCCGCCGCGCCCCCAGTTGCCTCCGACCTTGGC
CCGCGGCCGCCGGTGAGCCTAGACCCGCGCGTCTCCATTTACAGCACGCGCCGCCCGGTG
TTGGCGCGCACCCACGTCCAGGGCCGCGTCTACAACTTCCTCGAGCGTCCCACCGGCTGG
AAATGCTTCGTTTACCACTTCGCCGTCTTCCTCATCGTCCTGGTCTGCCTCATCTTCAGC
GTGCTGTCCACCATCGAGCAGTATGCCGCCCTGGCCACGGGGACTCTCTTCTGGATGGAG
ATCGTGCTGGTGGTGTTCTTCGGGACGGAGTACGTGGTCCGCCTCTGGTCCGCCGGCTGC
CGCAGCAAGTACGTGGGCCTCTGGGGGCGGCTGCGCTTTGCCCGGAAGCCCATTTCCATC
ATCGACCTCATCGTGGTCGTGGCCTCCATGGTGGTCCTCTGCGTGGGCTCCAAGGGGCAG
GTGTTTGCCACGTCGGCCATCAGGGGCATCCGCTTCCTGCAGATCCTGAGGATGCTACAC
GTCGACCGCCAGGGAGGCACCTGGAGGCTCCTGGGCTCCGTGGTCTTCATCCACCGCCAG
GAGCTGATAACCACCCTGTACATCGGCTTCCTGGGCCTCATCTTCTCCTCGTACTTTGTG
TACCTGGCTGAGAAGGACGCGGTGAACGAGTCAGGCCGCGTGGAGTTCGGCAGCTACGCA
GATGCGCTGTGGTGGGGGGTGGTCACAGTCACCACCATCGGCTATGGGGACAAGGTGCCC
CAGACGTGGGTCGGGAAGACCATCGCCTCCTGCTTCTCTGTCTTTGCCATCTCCTTCTTT
GCGCTCCCAGCGGGGATTCTTGGCTCGGGGTTTGCCCTGAAGGTGCAGCAGAAGCAGAGG
CAGAAGCACTTCAACCGGCAGATCCCGGCGGCAGCCTCACTCATTCAGACCGCATGGAGG
TGCTATGCTGCCGAGAACCCCGACTCCTCCACCTGGAAGATCTACATCCGGAAGGCCCCC
CGGAGCCACACTCTGCTGTCACCCAGCCCCAAACCCAAGAAGTCTGTGGTGGTAAAGAAA
AAAAAGTTCAAGCTGGACAAAGACAATGGGGTGACTCCTGGAGAGAAGATGCTCACAGTC
CCCCATATCACGTGCGACCCCCCAGAAGAGCGGCGGCTGGACCACTTCTCTGTCGACGGC
TATGACAGTTCTGTAAGGAAGAGCCCAACACTGCTGGAAGTGAGCATGCCCCATTTCATG
AGAACCAACAGCTTCGCCGAGGACCTGGACCTGGAAGGGGAGACTCTGCTGACACCCATC
ACCCACATCTCACAGCTGCGGGAACACCATCGGGCCACCATTAAGGTCATTCGACGCATG
CAGTACTTTGTGGCCAAGAAGAAATTCCAGCAAGCGCGGAAGCCTTACGATGTGCGGGAC
GTCATTGAGCAGTACTCGCAGGGCCACCTCAACCTCATGGTGCGCATCAAGGAGCTGCAG
AGGAGGCTGGACCAGTCCATTGGGAAGCCCTCACTGTTCATCTCCGTCTCAGAAAAGAGC
AAGGATCGCGGCAGCAACACGATCGGCGCCCGCCTGAACCGAGTAGAAGACAAGGTGACG
CAGCTGGACCAGAGGCTGGCACTCATCACCGACATGCTTCACCAGCTGCTCTCCTTGCAC
GGTGGCAGCACCCCCGGCAGCGGCGGCCCCCCCAGAGAGGGCGGGGCCCACATCACCCAG
CCCTGCGGCAGTGGCGGCTCCGTCGACCCTGAGCTCTTCCTGCCCAGCAACACCCTGCCC
ACCTACGAGCAGCTGACCGTGCCCAGGAGGGGCCCCGATGAGGGGTCCTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID KCNQ1 Link Image
Target 2 GenAtlas ID KCNQ1 Link Image
Target 2 HGNC ID HGNC:6294 Link Image
Target 2 Chromosome Location 11
Target 2 Locus 11p15.5
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Neyroud N, Richard P, Vignier N, Donger C, Denjoy I, Demay L, Shkolnikova M, Pesce R, Chevalier P, Hainque B, Coumel P, Schwartz K, Guicheney P: Genomic organization of the KCNQ1 K+ channel gene and identification of C-terminal mutations in the long-QT syndrome. Circ Res. 1999 Feb 19;84(3):290-7. [PubMed Link Image]
  2. Mohammad-Panah R, Demolombe S, Neyroud N, Guicheney P, Kyndt F, van den Hoff M, Baro I, Escande D: Mutations in a dominant-negative isoform correlate with phenotype in inherited cardiac arrhythmias. Am J Hum Genet. 1999 Apr;64(4):1015-23. [PubMed Link Image]
  3. Jongbloed RJ, Wilde AA, Geelen JL, Doevendans P, Schaap C, Van Langen I, van Tintelen JP, Cobben JM, Beaufort-Krol GC, Geraedts JP, Smeets HJ: Novel KCNQ1 and HERG missense mutations in Dutch long-QT families. Hum Mutat. 1999;13(4):301-10. [PubMed Link Image]
  4. Larsen LA, Christiansen M, Vuust J, Andersen PS: High-throughput single-strand conformation polymorphism analysis by automated capillary electrophoresis: robust multiplex analysis and pattern-based identification of allelic variants. Hum Mutat. 1999;13(4):318-27. [PubMed Link Image]
  5. Denjoy I, Lupoglazoff JM, Donger C, Berthet M, Richard P, Neyroud N, Villain E, Lucet V, Coumel P, Guicheney P: [Congenital long QT syndrome. The value of genetics in prognostic evaluation] Arch Mal Coeur Vaiss. 1999 May;92(5):557-63. [PubMed Link Image]
  6. Franqueza L, Lin M, Shen J, Splawski I, Keating MT, Sanguinetti MC: Long QT syndrome-associated mutations in the S4-S5 linker of KvLQT1 potassium channels modify gating and interaction with minK subunits. J Biol Chem. 1999 Jul 23;274(30):21063-70. [PubMed Link Image]
  7. Larsen LA, Fosdal I, Andersen PS, Kanters JK, Vuust J, Wettrell G, Christiansen M: Recessive Romano-Ward syndrome associated with compound heterozygosity for two mutations in the KVLQT1 gene. Eur J Hum Genet. 1999 Sep;7(6):724-8. [PubMed Link Image]
  8. Schroeder BC, Waldegger S, Fehr S, Bleich M, Warth R, Greger R, Jentsch TJ: A constitutively open potassium channel formed by KCNQ1 and KCNE3. Nature. 2000 Jan 13;403(6766):196-9. [PubMed Link Image]
  9. Schmitt N, Schwarz M, Peretz A, Abitbol I, Attali B, Pongs O: A recessive C-terminal Jervell and Lange-Nielsen mutation of the KCNQ1 channel impairs subunit assembly. EMBO J. 2000 Feb 1;19(3):332-40. [PubMed Link Image]
  10. Tranebjaerg L, Bathen J, Tyson J, Bitner-Glindzicz M: Jervell and Lange-Nielsen syndrome: a Norwegian perspective. Am J Med Genet. 1999 Sep 24;89(3):137-46. [PubMed Link Image]
  11. 10713961 Selyanko AA, Hadley JK, Wood IC, Abogadie FC, Jentsch TJ, Brown DA: Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors. J Physiol. 2000 Feb 1;522 Pt 3:349-55.
  12. 10728423 Chouabe C, Neyroud N, Richard P, Denjoy I, Hainque B, Romey G, Drici MD, Guicheney P, Barhanin J: Novel mutations in KvLQT1 that affect Iks activation through interactions with Isk. Cardiovasc Res. 2000 Mar;45(4):971-80.
  13. 10973849 Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT: Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 Sep 5;102(10):1178-85.
  14. 12522251 Chen YH, Xu SJ, Bendahhou S, Wang XL, Wang Y, Xu WY, Jin HW, Sun H, Su XY, Zhuang QN, Yang YQ, Li YB, Liu Y, Xu HJ, Li XF, Ma N, Mou CP, Chen Z, Barhanin J, Huang W: KCNQ1 gain-of-function mutation in familial atrial fibrillation. Science. 2003 Jan 10;299(5604):251-4.
  15. 8528244 Wang Q, Curran ME, Splawski I, Burn TC, Millholland JM, VanRaay TJ, Shen J, Timothy KW, Vincent GM, de Jager T, Schwartz PJ, Toubin JA, Moss AJ, Atkinson DL, Landes GM, Connors TD, Keating MT: Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet. 1996 Jan;12(1):17-23.
  16. 8818942 de Jager T, Corbett CH, Badenhorst JC, Brink PA, Corfield VA: Evidence of a long QT founder gene with varying phenotypic expression in South African families. J Med Genet. 1996 Jul;33(7):567-73.
  17. 8872472 Russell MW, Dick M 2nd, Collins FS, Brody LC: KVLQT1 mutations in three families with familial or sporadic long QT syndrome. Hum Mol Genet. 1996 Sep;5(9):1319-24.
  18. 8900283 Sanguinetti MC, Curran ME, Zou A, Shen J, Spector PS, Atkinson DL, Keating MT: Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel. Nature. 1996 Nov 7;384(6604):80-3.
  19. 9024139 Tanaka T, Nagai R, Tomoike H, Takata S, Yano K, Yabuta K, Haneda N, Nakano O, Shibata A, Sawayama T, Kasai H, Yazaki Y, Nakamura Y: Four novel KVLQT1 and four novel HERG mutations in familial long-QT syndrome. Circulation. 1997 Feb 4;95(3):565-7.
  20. 9108097 Yang WP, Levesque PC, Little WA, Conder ML, Shalaby FY, Blanar MA: KvLQT1, a voltage-gated potassium channel responsible for human cardiac arrhythmias. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4017-21.
  21. 9272155 van den Berg MH, Wilde AA, Robles de Medina EO, Meyer H, Geelen JL, Jongbloed RJ, Wellens HJ, Geraedts JP: The long QT syndrome: a novel missense mutation in the S6 region of the KVLQT1 gene. Hum Genet. 1997 Sep;100(3-4):356-61.
  22. 9302275 Wollnik B, Schroeder BC, Kubisch C, Esperer HD, Wieacker P, Jentsch TJ: Pathophysiological mechanisms of dominant and recessive KVLQT1 K+ channel mutations found in inherited cardiac arrhythmias. Hum Mol Genet. 1997 Oct;6(11):1943-9.
  23. 9305853 Jiang M, Tseng-Crank J, Tseng GN: Suppression of slow delayed rectifier current by a truncated isoform of KvLQT1 cloned from normal human heart. J Biol Chem. 1997 Sep 26;272(39):24109-12.
  24. 9312006 Chouabe C, Neyroud N, Guicheney P, Lazdunski M, Romey G, Barhanin J: Properties of KvLQT1 K+ channel mutations in Romano-Ward and Jervell and Lange-Nielsen inherited cardiac arrhythmias. EMBO J. 1997 Sep 1;16(17):5472-9.
  25. 9323054 Shalaby FY, Levesque PC, Yang WP, Little WA, Conder ML, Jenkins-West T, Blanar MA: Dominant-negative KvLQT1 mutations underlie the LQT1 form of long QT syndrome. Circulation. 1997 Sep 16;96(6):1733-6.
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Target 2 Drug References
  1. Li RA, Miake J, Hoppe UC, Johns DC, Marban E, Nuss HB: Functional consequences of the arrhythmogenic G306R KvLQT1 K+ channel mutant probed by viral gene transfer in cardiomyocytes. J Physiol. 2001 May 15;533(Pt 1):127-33. [PubMed Link Image]
  2. Ohya S, Asakura K, Muraki K, Watanabe M, Imaizumi Y: Molecular and functional characterization of ERG, KCNQ, and KCNE subtypes in rat stomach smooth muscle. Am J Physiol Gastrointest Liver Physiol. 2002 Feb;282(2):G277-87. [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.