Activation of human ether-a-go-go related gene (hERG) potassium channels by small molecules

Acta Pharmacologica Sinica

Volumn 32, Issue 6, 2011, Pages 781-788

  Zhou, Ping Zheng ^a,b   Babcock, Joseph ^c   Liu, Lian Qing ^b   Li, Min ^a,c   Gao, Zhao Bing ^a  

^a SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

^b SHENYANG INSTITUTE OF AUTOMATION   (China)

^c JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

activator; Human ether a go go related gene (hERG); ion channel; long QT syndrome (LQTS)

Indexed keywords

1,3 BIS(2 HYDROXY 5 TRIFLUOROMETHYLPHENYL)UREA; 2 [2 (3,4 DICHLOROPHENYL) 2,3 DIHYDRO 1H ISOINDOLIN 5 YLAMINO]NICOTINIC ACID; 2 [4 [2 (3,4 DICHLOROPHENYL)ETHYL]PHENYLAMINO]BENZOIC ACID; 2 METHYL 3 (3,5 DIIODO 4 CARBOXYMETHOXYBENZYL)BENZOFURAN; 3 NITRO N (4 PHENOXYPHENYL)BENZAMIDE; 4 [3 (6 METHOXYQUINOLIN 4 YL) 3 OXOPROPYL] 1 [3 (2,3,5 TRIFLUOROPHENYL)PROP 2 YN 1 YL]PIPERIDINE 3 CARBOXYLIC ACID; [4 [4 (5 TRIFLUOROMETHYL 1H PYRAZOL 3 YL)PHENYL]CYCLOHEXYL]ACETIC ACID; A 935142; ANILINE DERIVATIVE; ASTEMIZOLE; BENZOFURAN DERIVATIVE; CISAPRIDE; DROPERIDOL; GREPAFLOXACIN; GREPAFLOXICIN; ICA 105574; KB 130015; LEVOMETHADONE; LEVOMETHADYL; LIDOFLAZINE; MALLATOXIN; N [4 BROMO 2 (1H TETRAZOL 5 YL)PHENYL] N' (3 TRIFLUOROMETHYLPHENYL)UREA; NICOTINIC ACID DERIVATIVE; NS 1643; NS 3623; PD 118057; PD 307243; PIPERIDINE DERIVATIVE; POTASSIUM CHANNEL HERG; PYRAZOLE DERIVATIVE; RPR 260243; SERTINDOLE; TERFENADINE; UNCLASSIFIED DRUG; UREA DERIVATIVE;

CONFERENCE PAPER; DRUG ACTIVITY; DRUG RECALL; HEART REPOLARIZATION; HUMAN; LONG QT SYNDROME; NONHUMAN; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION;

ANIMALS; BINDING SITES; ETHER-A-GO-GO POTASSIUM CHANNELS; HUMANS; ION CHANNEL GATING; LONG QT SYNDROME; MOLECULAR STRUCTURE; SMALL MOLECULE LIBRARIES;

EID: 79958164959     PISSN: 16714083     EISSN: 17457254     Source Type: Journal    
DOI: 10.1038/aps.2011.70     Document Type: Conference Paper

References (40)

1. Warmke JW, Ganetzky B. A family of potassium channel genes related to eag in Drosophila and mammals. Proc Natl Acad Sci U S A 1994;91:3438-42. (Pubitemid 24130252)
2. Sanguinetti MC, Jiang C, Curran ME, Keating MT. A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 1995;81:299-307.
3. Shen XZ, Wu J, Lin JJ. HERG and arrhythmia. Adv Cardio vasc Dis 2008;29:436-40.
4. Lagrutta AA, Trepakova ES, Salata JJ. The hERG channel and risk of drug-acquired cardiac arrhythmia: an overview. Curr Top Med Chem 2008;8:1102-12.
5. + channels: function and dysfunction. Prog Biophys Mol Biol 2008;98:137-48.
6. + channel: progress in understanding the molecular basis of its unusual gating kinetics. Eur Biophys J 2004;33:89-97. (Pubitemid 38987095)
7. + channel. Novartis Found Symp 2005;266:46-52.
8. Smith PL, Yellen G. Fast and slow voltage sensor movements in HERG potassium channels. J Gen Physiol 2002;119:275-93. (Pubitemid 34522240)
9. + channel: the S4 domain is loosely packed and likely to be lipid exposed. J Physiol 2005;569:367-79. (Pubitemid 41830108)
10. +]: a tale of two inactivation mechanisms. Neuron 1995;15:951-60.
11. Smith PL, Baukrowitz T, Yellen G. The inward rectification mechanism of the HERG cardiac potassium channel. Nature 1996;379:833-6. (Pubitemid 26067726)
12. Jiang M, Zhang M, Maslennikov IV, Liu J, Wu DM, Korolkova YV, et al. Dynamic conformational changes of extracellular S5-P linkers in the hERG channel. J Physiol 2005;569:75-89. (Pubitemid 41701377)
13. Hedley PL, Jørgensen P, Schlamowitz S, Wangari R, Moolman-Smook J, Brink PA, et al. The genetic basis of long QT and short QT syndromes: a mutation update. Hum Mutat 2009;30:1486-511.
14. Roden DM, Lazzara R, Rosen M, Schwartz PJ, Towbin J, Vincent GM. Multiple mechanisms in the long-QT syndrome. Current knowledge, gaps, and future directions. The SADS Foundation Task Force on LQTS. Circulation 1996;94:1996-2012.
15. + currents and cardiac repolarization. J Mol Cell Cardiol 2010;48:37-44.
16. Kaufman ES, Ficker E. Is restoration of intracellular trafficking clinically feasible in the long QT syndrome? The example of HERG mutations. J Cardiovasc Electrophysiol 2003;14:320-2. (Pubitemid 36444478)
17. Gong Q, Jones MA, Zhou, Z. Mechanisms of pharmacological rescue of trafficking-defective hERG mutant channels in human long QT syndrome. J Biol Chem 2006;281:4069-74. (Pubitemid 43847832)
18. Berger SI, Ma'ayan A, Iyengar R. Systems pharmacology of arrhythmias. Sci Signal 2010;3: ra30.
19. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med 2004;350:1013-22 (Pubitemid 38269278)
20. + channel, the target of anti-arrhythmias drugs. Yao Xue Xue Bao 2007;42:687-91
21. Wulff H, Castle NA, Pardo LA. Voltage-gated potassium channels as therapeutic targets. Nat Rev Drug Discov 2009;8:982-1001
22. + channel. Mol Pharmacol 2005;67:827-36 (Pubitemid 40365330)
23. Perry M, Sanguinetti MC. A single amino acid difference between ether-a-go-go-related gene channel subtypes determines differentia sensitivity to a small molecule activator. Mol Pharmacol 2008;73 1044-51 (Pubitemid 351439186)
24. Perry M, Sachse FB, Sanguinetti MC. Structural basis of action for a human ether-a-go-go-related gene 1 potassium channel activator. Proc Natl Acad Sci U S A 2007;104:13827-32 (Pubitemid 350003405)
25. Zhou J, Augelli-Szafran CE, Bradley JA, Chen X, Koci BJ, Volberg WA, et al. Novel potent human ether-a-go-go-related gene (hERG) potassium channel enhancers and their in vitro antiarrhythmic activity. Mo Pharmacol 2005;68:876-84 (Pubitemid 41206044)
26. Gordon E, Lozinskaya IM, Lin Z, Semus SF, Blaney FE, Willette RN et al. 2-[2-(3, 4-dichloro-phenyl)-2, 3-dihydro-1 H-isoindol-5-ylamino]-nicotinic acid (PD-307243) causes instantaneous current through human ether-a-go-go-related gene potassium channels. Mo Pharmacol 2008;73:639-51 (Pubitemid 351397869)
27. Casis O, Olesen SP, Sanguinetti MC. Mechanism of action of a nove human ether-a-go-go-related gene channel activator. Mol Pharmaco 2006;69:658-65 (Pubitemid 43121963)
28. Hansen RS, Diness TG, Christ T, Wettwer E, Ravens U, Olesen SP, et al. Biophysical characterization of the new human ether-a-go-go-related gene channel opener NS3623 [N-(4-bromo-2-(1H-tetrazol-5-yl)-phenyl)-N′-(3′- trifluoromethylphenyl) urea]. Mol Pharmacol 2006 70:1319-29 (Pubitemid 44435984)
29. Su Z, Limberis J, Souers A, Kym P, Mikhail A, Houseman K, et al. Electrophysiologic characterization of a novel hERG channel activator Biochem Pharmacol 2009;77:1383-90
30. Gerlach AC, Stoehr SJ, Castle NA. Pharmacological removal of human ether-a-go-go-related gene potassium channel inactivation by 3-nitro-N-(4-phenoxyphenyl) benzamide (ICA-105574). Mol Pharmacol 2010;77:58-68.
31. Gessner G, Macianskiene R, Starkus JG, Schonherr R, Heinemann SH. The amiodarone derivative KB130015 activates hERG1 potassium channels via a novel mechanism. Eur J Pharmacol 2010;632:52-9.
32. Zeng H, Lozinskaya IM, Lin Z, Willette RN, Brooks DP, Xu X, et al. Mallotoxin is a novel human ether-a-go-go-related gene (hERG) potassium channel activator. J Pharmacol Exp Ther 2006;319:957-62.
33. + conductance. Proc Natl Acad Sci U S A 2009;106:20075-80.
34. Xu X, Recanatini M, Roberti M, Tseng GN. Probing the binding sites and mechanisms of action of two human ether-a-go-go-related gene channel activators, 1, 3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643) and 2-[2-(3, 4-dichloro-phenyl)-2, 3-dihydro-1H-isoindol-5-ylamino]-nicotinic acid (PD307243). Mol Pharmacol 2008;73:1709-21. (Pubitemid 351724359)
35. -conductance blocker, ameliorates erythrocyte dehydration in transgenic SAD mice: a possible new therapeutic approach for sickle cell disease. Blood 2001;97:1451-7. (Pubitemid 32183772)
36. + channel blockade by the antiarrhythmic agent dronedarone: resistance to mutations of the S6 residues Y652 and F656. Biochem Biophys Res Commun 2004;325:883-91. (Pubitemid 39487955)
37. Perry M, Sanguinetti M, Mitcheson J. Revealing the structural basis of action of hERG potassium channel activators and blockers. J Physiol 2010;588:3157-67.
38. Schwartz PJ. The congenital long QT syndromes from genotype to phenotype: clinical implications. J Intern Med 2006;259:39-47.
39. Gow RM. Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. Circulation 2001;103: E24.
40. Bjerregaard P, Jahangir A, Gussak I. Targeted therapy for short QT syndrome. Expert Opin Ther Targets 2006;10:393-400. (Pubitemid 43949953)