Target Information

Target General Infomation
Target ID
T49526
Former ID
TTDS00148
Target Name
Potassium voltage-gated channel subfamily KQT member 1
Gene Name
KCNQ1
Synonyms
IKs producing slow voltage-gated potassium channel alpha subunit KvLQT1; KCNQ1 channel; KQT-like 1; Kv7.1; Voltage-gated potassium channel subunit Kv7.1; KCNQ1
Target Type
Successful
Disease Hypertension [ICD9: 401; ICD10: I10-I16]
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 oxotremorinem strongly suppresses kcnq1/kcne1.
BioChemical Class
Voltage-gated ion channel
Target Validation
T49526
UniProt ID
P51787
Sequence
MAAASSPPRAERKRWGWGRLPGARRGSAGLAKKCPFSLELAEGGPAGGALYAPIAPGAPG
PAPPASPAAPAAPPVASDLGPRPPVSLDPRVSIYSTRRPVLARTHVQGRVYNFLERPTGW
KCFVYHFAVFLIVLVCLIFSVLSTIEQYAALATGTLFWMEIVLVVFFGTEYVVRLWSAGC
RSKYVGLWGRLRFARKPISIIDLIVVVASMVVLCVGSKGQVFATSAIRGIRFLQILRMLH
VDRQGGTWRLLGSVVFIHRQELITTLYIGFLGLIFSSYFVYLAEKDAVNESGRVEFGSYA
DALWWGVVTVTTIGYGDKVPQTWVGKTIASCFSVFAISFFALPAGILGSGFALKVQQKQR
QKHFNRQIPAAASLIQTAWRCYAAENPDSSTWKIYIRKAPRSHTLLSPSPKPKKSVVVKK
KKFKLDKDNGVTPGEKMLTVPHITCDPPEERRLDHFSVDGYDSSVRKSPTLLEVSMPHFM
RTNSFAEDLDLEGETLLTPITHISQLREHHRATIKVIRRMQYFVAKKKFQQARKPYDVRD
VIEQYSQGHLNLMVRIKELQRRLDQSIGKPSLFISVSEKSKDRGSNTIGARLNRVEDKVT
QLDQRLALITDMLHQLLSLHGGSTPGSGGPPREGGAHITQPCGSGGSVDPELFLPSNTLP
TYEQLTVPRRGPDEGS
Drugs and Mode of Action
Drug(s) Indapamide Drug Info Approved Hypertension [538270], [542217]
L-768673 Drug Info Terminated Discovery agent [546611]
Blocker (channel blocker) (3R,4S)-293B Drug Info [526219]
3S,4R-293B Drug Info [526219]
IKs124 Drug Info [527319]
XE991 Drug Info [525778]
Inhibitor HMR-1556 Drug Info [526979]
L-768673 Drug Info [534526]
N-(2-Diethylamino-ethyl)-4-hexyloxy-benzamide Drug Info [526184]
N-(3,3-Dimethyl-butyl)-4-hexyloxy-benzamide Drug Info [526184]
N-(3,3-Dimethyl-butyl)-4-indol-1-yl-benzamide Drug Info [526184]
N-(3,3-Dimethyl-cyclopentyl)-4-hexyloxy-benzamide Drug Info [526184]
Blocker Indapamide Drug Info [536209]
L-735,821 Drug Info [535746]
Activator ML277 Drug Info [532012]
R-L3 Drug Info [534668]
zinc pyrithione Drug Info [528790]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Adrenergic signaling in cardiomyocytes
Cholinergic synapse
Gastric acid secretion
Pancreatic secretion
Protein digestion and absorption
Vibrio cholerae infection
PathWhiz Pathway Muscle/Heart Contraction
Reactome Voltage gated Potassium channels
WikiPathways SIDS Susceptibility Pathways
Potassium Channels
miR-targeted genes in muscle cell - TarBase
miR-targeted genes in lymphocytes - TarBase
TarBasePathway
References
Ref 538270FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 074299.
Ref 542217(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7203).
Ref 546611Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009178)
Ref 525778Molecular basis for differential sensitivity of KCNQ and I(Ks) channels to the cognitive enhancer XE991. Mol Pharmacol. 2000 Jun;57(6):1218-23.
Ref 526184J Med Chem. 2001 Nov 8;44(23):3764-7.Design and synthesis of 4-substituted benzamides as potent, selective, and orally bioavailable I(Ks) blockers.
Ref 526219A kinetic study on the stereospecific inhibition of KCNQ1 and I(Ks) by the chromanol 293B. Br J Pharmacol. 2001 Dec;134(8):1647-54.
Ref 526979J Med Chem. 2004 Mar 11;47(6):1303-14.Selective optimization of side activities: another way for drug discovery.
Ref 527319Heteromeric KCNE2/KCNQ1 potassium channels in the luminal membrane of gastric parietal cells. J Physiol. 2004 Dec 1;561(Pt 2):547-57. Epub 2004 Oct 7.
Ref 528790Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Nat Chem Biol. 2007 May;3(5):287-96. Epub 2007 Apr 15.
Ref 532012Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide, ML277, as a novel, potent and selective K(v)7.1 (KCNQ1) potassium channel activator. Bioorg Med Chem Lett. 2012 Sep 15;22(18):5936-41.
Ref 534526J Med Chem. 1997 Nov 21;40(24):3865-8.Class III antiarrhythmic activity in vivo by selective blockade of the slowly activating cardiac delayed rectifier potassium current IKs by (R)-2-(2,4-trifluoromethyl)-N-[2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)- 2, 3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]acetamide.
Ref 534668A novel benzodiazepine that activates cardiac slow delayed rectifier K+ currents. Mol Pharmacol. 1998 Jul;54(1):220-30.
Ref 535746Molecular determinants of KCNQ1 channel block by a benzodiazepine. Mol Pharmacol. 2003 Jul;64(1):70-7.
Ref 536209Indapamide induces apoptosis of GH3 pituitary cells independently of its inhibition of voltage-dependent K+ currents. Eur J Pharmacol. 2006 Apr 24;536(1-2):78-84. Epub 2006 Mar 2.

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