Understanding the structure-activity relationship of the human ether-a-go-go-related gene cardiac K+ channel. A model for bad behavior

Journal of Medicinal Chemistry

Volumn 46, Issue 11, 2003, Pages 2017-2022

  Pearlstein, Robert ^a   Vaz, Roy ^a   Rampe, David ^a  

^a SANOFI   (France)

Author keywords

[No Author keywords available]

Indexed keywords

1' (6 CYANO 1,2,3,4 TETRAHYDRO 2 NAPHTHYL) 3,4 DIHYDRO 6 METHANESULFONAMIDOSPIRO[2H 1 BENZOPYRAN 2,4' PIPERIDIN] 4 OL; ANTIARRHYTHMIC AGENT; ASTEMIZOLE; CALCIUM CHANNEL; CISAPRIDE; GREPAFLOXACIN; ION CHANNEL; LORATADINE; MACROLIDE; OLANZAPINE; PIMOZIDE; POTASSIUM CHANNEL; POTASSIUM CHANNEL BLOCKING AGENT; QUINOLINE DERIVED ANTIINFECTIVE AGENT; SERTINDOLE; SODIUM CHANNEL; TERFENADINE; THIORIDAZINE;

AMINO ACID COMPOSITION; CELL MEMBRANE TRANSPORT; DRUG BINDING; GENE; HEART ARRHYTHMIA; HEART MUSCLE CELL; HEART MUSCLE POTENTIAL; HUMAN; HUMAN ETHER A GO GO RELATED GENE; LONG QT SYNDROME; NONHUMAN; PHARMACOPHORE; POTASSIUM TRANSPORT; SHORT SURVEY; STRUCTURE ACTIVITY RELATION; TORSADE DES POINTES;

CATION TRANSPORT PROTEINS; DNA-BINDING PROTEINS; ETHER-A-GO-GO POTASSIUM CHANNELS; HUMANS; LONG QT SYNDROME; MODELS, MOLECULAR; PHARMACEUTICAL PREPARATIONS; POTASSIUM CHANNELS; POTASSIUM CHANNELS, VOLTAGE-GATED; STRUCTURE-ACTIVITY RELATIONSHIP; TORSADES DE POINTES; TRANS-ACTIVATORS;

EID: 0038248920     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0205651     Document Type: Short Survey

References (22)

1. Ben-David, J.; Zipes, D. P. Torsades de pointes and proarrhythmia. Lancet 1993, 341, 1578-1582.
2. Brown, A. M.; Rampe, D. Drug-induced long QT syndrome: Is HERG the root of all evil? Pharm. News 2000, 7, 15-20.
3. Kr potassium channel. Cell 1995, 81, 299-307.
4. Roy, M.-L.; Dumaine, R.; Brown, A. M. HERG, a primary human ventricular target of the nonsedating antihistamine terfenadine. Circulation 1996, 94, 817-823.
5. Zhou, Z.; Vorperian, V. R.; Gong, Q.; Zhang, S.; January, C. T. Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole. J. Cardiovasc. Electrophysiol. 1999, 10, 836-843.
6. Kongsamut, S.; Kang, J.; Chen, X.-L.; Roehr, J.; Rampe, D. A comparison of the receptor binding and HERG channel affinities for a series of antipsychotic drugs. Eur. J. Pharmacol. 2002, 450, 37-41.
7. + channels. Eur. J. Pharmacol. 2003, 458, 25-29.
8. + channel HERG. Mol. Pharmacol. 2001, 59, 122-126.
9. Volberg, W. A.; Koci, B. J.; Su, W.; Lin, J.; Zhou, J. Blockade of human cardiac potassium channel human ether-a-go-go-related gene (HERG) by macrolide antibiotics. J. Pharmacol. Exp. Ther. 2002, 302, 320-327.
10. + conduction and selectivity, Science 1998, 280, 69-77.
11. Jiang, Y.; Lee, A.; Chen, J.; Cadene, M.; Chait, B. T.; MacKinnon, R. Crystal structure and mechanism of a calcium-gated potassium channel. Nature 2002, 417, 515-522.
12. Jiang, Y.; Lee, A.; Chen, J.; Cadene, M.; Chait, B. T.; MacKinnon, R. The open pore conformation of potassium channels. Nature 2002, 417, 523-526.
13. Pearlstein, R. A.; Vaz, R. J.; Kang, J.; Xiao-Liang, C.; Preobrazhenskaya, M.; Shchekotikhin, A. E.; Korolev, A. M.; Lysenkova, L. N.; Miroshnikova, O. V.; Hendrix, J.; Rampe, D. A structure based coupled with a CoMSIA based explanation of the inhibition of the HERG potassium channel, Bioorg. Med. Chem. Lett., in press.
14. Mitcheson, J. S.; Chen, J.; Lin, M.; Culberson, C.; Sanguinetti, M. C. A structural basis for drug-induced long QT syndrome. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 12329-123333.
15. Keating, M. T.; Sanguinetti, M. C. Molecular and cellular mechanisms of cardiac arrhythmias. Cell 2001, 104, 569-580.
16. Morgan, T. K.; Sullivan, M. E. An overview of class III electrophysiological agents: A new generation of antiarrhythmic therapy. In Progress in Medicinal Chemistry; Ellis, G. P., Luscombe, D. K., Eds.; Elsevier Science Publishers B.V.: Amsterdam, 1992; Vol. 29, pp 65-108.
17. Ekins, S.; Crumb, W. J.; Sarazan, R. D.; Wikel, J. H.; Wrighton, S. A. Three-dimensional quantitative structure-activity relationship for inhibition of human ether-a-go-go-related gene potassium channel. J. Pharmacol. Exp. Ther. 2002, 301, 427-434.
18. Roche, O.; Trube, G.; Zuegge, J.; Pflimlin, P.; Alanine, A.; Schneider, G. A virtual screening method for prediction of the hERG potassium channel liability of compound libraries, Chem-BioChem 2002, 3, 455-459.
19. + channel blockers. J. Med. Chem. 2002, 45, 3844-3853.
20. + channels in human heart: comparison with terfenadine under physiological conditions. J. Pharmacol. Exp. Ther. 2000, 292, 261-264.
21. 2+ channels (SOC's). Biochem. Pharmacol. 2001, 62, 1229-1238.
22. Chen, J.; Seebohm, G.; Sanguinetti, M. C. Position of aromatic residues in the S6 domain, not inactivation, dictates cisapride sensitivity of HERG and eag potassion channels. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 12461-12466.