Therapeutic Targets Database
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TTD Target ID: TTDS00147

Target Information
NamePotassium voltage-gated channel subfamily H member 2    
Type of targetSuccessful target    
SynonymsEag homolog    
Eag related protein 1    
Erg1    
Ether-a-go-go related gene potassium channel 1    
Ether-a-go-go related protein 1    
H-ERG    
HERG K+ channel    
Voltage-gated potassium channel subunit Kv11.1    
DiseaseCardiac arrhythmias
[ICD9: 427   ICD10: I47-I49]
[1]
Drug(s)AmiodaroneApprovedTachyarrhythmias[2][3]
DofetilideApprovedMaintenance of normal sinus rhythm[4][5]
PropafenoneApprovedTachyarrhythmias[6]
HP-184Phase IIMultiple Sclerosis[7]
BioChemical ClassVoltage-gated channel    
UniProt IDQ12809
PDB Structure1BYW; 1UJL; 2L0W; 2L1M; 2L4R; 2LE7; 4HP9; 4HQA.    
FunctionPore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. channel properties are modulated by camp and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (ikr).    
SequenceMPVRRGHVAPQNTFLDTIIRKFEGQSRKFIIANARVENCAVIYCNDGFCELCGYSRAEVM QRPCTCDFLHGPRTQRRAAAQIAQALLGAEERKVEIAFYRKDGSCFLCLVDVVPVKNEDG AVIMFILNFEVVMEKDMVGSPAHDTNHRGPPTSWLAPGRAKTFRLKLPALLALTARESSV RSGGAGGAGAPGAVVVDVDLTPAAPSSESLALDEVTAMDNHVAGLGPAEERRALVGPGSP PRSAPGQLPSPRAHSLNPDASGSSCSLARTRSRESCASVRRASSADDIEAMRAGVLPPPP RHASTGAMHPLRSGLLNSTSDSDLVRYRTISKIPQITLNFVDLKGDPFLASPTSDREIIA PKIKERTHNVTEKVTQVLSLGADVLPEYKLQAPRIHRWTILHYSPFKAVWDWLILLLVIY TAVFTPYSAAFLLKETEEGPPATECGYACQPLAVVDLIVDIMFIVDILINFRTTYVNANE EVVSHPGRIAVHYFKGWFLIDMVAAIPFDLLIFGSGSEELIGLLKTARLLRLVRVARKLD RYSEYGAAVLFLLMCTFALIAHWLACIWYAIGNMEQPHMDSRIGWLHNLGDQIGKPYNSS GLGGPSIKDKYVTALYFTFSSLTSVGFGNVSPNTNSEKIFSICVMLIGSLMYASIFGNVS AIIQRLYSGTARYHTQMLRVREFIRFHQIPNPLRQRLEEYFQHAWSYTNGIDMNAVLKGF PECLQADICLHLNRSLLQHCKPFRGATKGCLRALAMKFKTTHAPPGDTLVHAGDLLTALY FISRGSIEILRGDVVVAILGKNDIFGEPLNLYARPGKSNGDVRALTYCDLHKIHRDDLLE VLDMYPEFSDHFWSSLEITFNLRDTNMIPGSPGSTELEGGFSRQRKRKLSFRRRTDKDTE QPGEVSALGPGRAGAGPSSRGRPGGPWGESPSSGPSSPESSEDEGPGRSSSPLRLVPFSS PRPPGEPPGGEPLMEDCEKSSDTCNPLSGAFSGVSNIFSFWGDSRGRQYQELPRCPAPTP SLLNIPLSSPGRRPRGDVESRLDALQRQLNRLETRLSADMATVLQLLQRQMTLVPPAYSA VTTPGPGPTSTSPLLPVSPLPTLTLDSLSQVSQFMACEELPPGAPELPQEGPTRRLSLPG QLGALTSQPLHRHGSDPGS
Target ValidationClick to Find Target Validation Information.    
Inhibitor (1R,5R)-30-OXO-19-OXA-2,6,10,12-TETRAAZAHEXACYCLO[18.6.2.1^{2,5}.1^{14,18}.0^{8,12}.0^{23,27}]TRIACONTA-8,10,14[8]
(2R)-N-[9]
(E)-2-[10]
(R)-3-[11]
(R)-6-[12]
(R)-N-isobutyl-N-[13]
(R)-ONDANSETRON[14]
(S)-3-[11]
1,6-bis (4-[15]
1,6-bis (4-[15]
1,6-bis (4-m-tolylpiperazin-1-yl)hexane[15]
1,6-bis (4-phenylpiperazin-1-yl)hexane[15]
1- (1-[16]
1- (1-[16]
1- (1-phenyl-2-[16]
1- (2-[16]
1- (2-[11]
1- (3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane[17]
1- (4-p-Tolyl-butyl)-piperidine[18]
2-Phenyl-3-piperidin-3-yl-1H-indole[19]
2-Phenyl-3-piperidin-4-yl-1H-indole[19]
2-[4- (2-Piperidin-1-ylethyl)phenoxy]benzothiazole[20]
3 9-DIHYDRO-N-DESMETHYL-N-ISOPROPYLERYTHROMYCIN A[21]
3- (1-Benzyl-piperidin-3-yl)-2-phenyl-1H-indole[19]
3- (1-Methyl-piperidin-2-yl)-2-phenyl-1H-indole[19]
3- (1-Methyl-piperidin-3-yl)-2-phenyl-1H-indole[19]
3- (1-Phenethyl-piperidin-3-yl)-2-phenyl-1H-indole[19]
3- (1-Phenethyl-piperidin-4-yl)-2-phenyl-1H-indole[19]
3- (1H-indol-3-yl)-N-methyl-3-phenylpropan-1-amine[17]
3- (benzo[b]thiophen-5-yl)-3-benzylpyrrolidine[17]
3- (dimethylamino)-1-[22]
4- ([11]
4- (2-thienyl)benzene-1,2-diamine[23]
4- (3-thienyl)benzene-1,2-diamine)[23]
4- (Spiro[chromene-2,4'-piperidine]-4-yl)benzamide[24]
4- (Spiro[chromene-2,4'-piperidine]-4-yl)phenol[25]
4- (p-Tolyl)spiro[chromene-2,4'-piperidine][25]
4-Benzenesulfonyl-1- (3-phenyl-propyl)-piperidine[26]
4-Benzenesulfonyl-1-phenethyl-piperidine[26]
4-Phenylspiro[chromene-2,4'-piperidine][25]
5- (3-[17]
5- (3-BENZYLPYRROLIDIN-3-YL)-1H-INDOLE [17]
5- (3-benzylpyrrolidin-3-yl)-1-methyl-1H-indole[17]
5- (3-butylpyrrolidin-3-yl)-1H-indole[17]
5-Chloro-3-ethyl-1- (4-fluoro-phenyl)-1H-indole[27]
6- (4-CHLOROPHENYL)-7-[9]
7- (piperidin-4-ylmethoxy)-2-naphthonitrile[11]
8-azabicyclo[3.2.1]octan-3-yloxy-benzamide[28]
ABT-229[21]
ADS-103253[29]
AZD-5438[30]
BETRIXABAN[31]
BI-1356[32]
BMS-540215[33]
BMS-645737[34]
DESETHYL AMODIAQUINE[35]
DESMETHEYLASTEMIZOLE[36]
DESMETHYLOLANZAPINE[8]
E-4031[37]
EMD-281014[38]
GSK-369796[35]
GW-3430[39]
ISOQUINE[35]
JNJ-10392980[20]
MDL-74156[36]
MK-1925[40]
MK-499[27]
MK-499[41]
N- (4-[42]
N- (6-[9]
N- (piperidin-4-yl)-N-propyl-2-naphthamide[13]
N-DESMETHYLCLOZAPINE[8]
N-[6- (4-CHLOROPHENYL)-7-[41]
NIFEVIROC[43]
NITD609[44]
NPS-2143,   SB-262470A[45]
PF-526014[16]
R-dimethindene[46]
RP-58866[36]
RWJ-671818[47]
TERIKALANT[36]
VESNARINONE[36]
VOLINANSERIN[48]
ZIPRASIDONE HYDROCHLORIDE[36]
[1- (4-p-Tolyl-butyl)-piperidin-4-yl]-methanol[18]
BlockerAlmokalant[49]
Amiodarone[2][3]
Desmethylastemizole[50]
Dofetilide[4][5]
HP-184[7]
Norastemizole[50]
Propafenone[6]
MultitargetHP-184[7]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
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Ref 2Potassium channel currents in rat mesenchymal stem cells and their possible roles in cell proliferation. Clin Exp Pharmacol Physiol. 2008 Sep;35(9):1077-84. Epub 2008 May 25. To Reference
Ref 3Theoretical possibilities for the development of novel antiarrhythmic drugs. Curr Med Chem. 2004 Jan;11(1):1-11. To Reference
Ref 4Combined pharmacological block of I(Kr) and I(Ks) increases short-term QT interval variability and provokes torsades de pointes. Br J Pharmacol. 2007 Aug;151(7):941-51. Epub 2007 May 29. To Reference
Ref 5Discovery of a small molecule activator of the human ether-a-go-go-related gene (HERG) cardiac K+ channel. Mol Pharmacol. 2005 Mar;67(3):827-36. Epub 2004 Nov 17. To Reference
Ref 6The low-potency, voltage-dependent HERG blocker propafenone--molecular determinants and drug trapping. Mol Pharmacol. 2004 Nov;66(5):1201-12. Epub 2004 Aug 12. To Reference
Ref 7Emerging drugs for spinal cord injury. Expert Opin Emerg Drugs. 2008 Mar;13(1):63-80. To Reference
Ref 8J Med Chem. 2009 Jul 23;52(14):4266-76.Side chain flexibilities in the human ether-a-go-go related gene potassium channel (hERG) together with matched-pair binding studies suggest a new binding mode for channel blockers. To Reference
Ref 9Bioorg Med Chem Lett. 2010 Jun 15;20(12):3750-4. Epub 2010 Apr 21.Dihydro-pyrano[2,3-b]pyridines and tetrahydro-1,8-naphthyridines as CB1 receptor inverse agonists: synthesis, SAR and biological evaluation. To Reference
Ref 10Bioorg Med Chem Lett. 2007 May 1;17(9):2643-8. Epub 2007 Feb 2.2,5-Disubstituted pyridines: the discovery of a novel series of 5-HT2A ligands. To Reference
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Ref 27Bioorg Med Chem Lett. 2003 May 19;13(10):1829-35.Characterization of HERG potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches. To Reference
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Ref 33J Med Chem. 2006 Apr 6;49(7):2143-6.Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5- methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan- 2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor. To Reference
Ref 34Bioorg Med Chem Lett. 2008 May 1;18(9):2985-9. Epub 2008 Mar 22.Discovery and preclinical studies of 5-isopropyl-6-(5-methyl-1,3,4-oxadiazol-2-yl)-N-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (BMS-645737), an in vivo active potent VEGFR-2 inhibitor. To Reference
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Ref 40Bioorg Med Chem Lett. 2009 Aug 15;19(16):4729-32. Epub 2009 Jun 17.Identification of MK-1925: a selective, orally active and brain-penetrable opioid receptor-like 1 (ORL1) antagonist. To Reference
Ref 41J Med Chem. 2010 May 27;53(10):4028-37.Discovery of N-[(4R)-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridin-4-yl]-5-methyl-1H-pyrazole-3-carboxamide (MK-5596) as a novel cannabinoid-1 receptor (CB1R) inverse agonist for the treatment of obesity. To Reference
Ref 42J Med Chem. 2007 Feb 22;50(4):807-19. Epub 2007 Jan 24.Identification and characterization of 4-methylbenzyl 4-[(pyrimidin-2-ylamino)methyl]piperidine-1-carboxylate, an orally bioavailable, brain penetrant NR2B selective N-methyl-D-aspartate receptor antagonist. To Reference
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Ref 48Bioorg Med Chem Lett. 2010 Jun 15;20(12):3708-12. Epub 2010 Apr 24.Non-basic ligands for aminergic GPCRs: the discovery and development diaryl sulfones as selective, orally bioavailable 5-HT2A receptor antagonists for the treatment of sleep disorders. To Reference
Ref 49Teratogenicity by the hERG potassium channel blocking drug almokalant: use of hypoxia marker gives evidence for a hypoxia-related mechanism mediated via embryonic arrhythmia. Toxicol Appl Pharmacol. 2003 Dec 1;193(2):168-76. To Reference
Ref 50Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole. J Cardiovasc Electrophysiol. 1999 Jun;10(6):836-43. To Reference



 

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Professor in Department of Pharmacy
National University of Singapore, Singapore


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