Inhibitory effect of carboxylic acid group on hERG binding

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 21, 2006, Pages 5507-5512

  Zhu, Bing Yan ^a,b   Jia, Zhaozhong J ^a,b   Zhang, Penglie ^b,c   Su, Ting ^a,b   Huang, Wenrong ^b,g   Goldman, Erick ^b,d   Tumas, Daniel ^b,e   Kadambi, Vic ^b,f   Eddy, Priya ^b,f   Sinha, Uma ^a,b   Scarborough, Robert M ^a,b   Song, Yonghong ^a,b  

^a Portola Pharmaceuticals Inc   (United States)

^b GENENTECH INC   (United States)

^c ChemoCentryx Inc   (United States)

^d EXELIXIS INC   (United States)

^e Gilead   (United States)

^f MILLENNIUM PHARMACEUTICALS INC   (United States)

^g FOLEY AND LARDNER LLP   (United States)

Author keywords

Carboxylic acid group; hERG channel binding; hERG channel blocking; Inhibitory effect

Indexed keywords

ACRYLAMIDE DERIVATIVE; BENZAMIDINE DERIVATIVE; CARBOXYLIC ACID; CETIRIZINE; GREPAFLOXACIN; PIPERAZINE DERIVATIVE; POTASSIUM CHANNEL HERG; PROBUCOL; PROBUCOL SUCCINATE; PYRAZOLE DERIVATIVE; SULFONAMIDE; TERFENADINE;

ARTICLE; ELECTRICITY; INHIBITION KINETICS; PROTEIN BINDING; PROTEIN INTERACTION;

BENZAMIDINES; CARBOXYLIC ACIDS; ETHER-A-GO-GO POTASSIUM CHANNELS; FACTOR XA; HUMANS;

EID: 33748770143     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.08.039     Document Type: Article

References (28)

1. Netzer R., Ebneth A., Bischoff U., and Pongs O. Drug Discovery Today 6 (2001) 78
2. Pearlstein R.A., Vaz R.J., Kang J., Chen X.-L., Preobrazhenskaya M., Shchekotikhin A.E., Korolev A.M., Lysenkova L.N., Miroshnikova O.V., Hendrix J., and Rampe D. Bioorg. Med. Chem. Lett. 13 (2003) 1829
3. Haverkamp W., et al. Cardiovasc. Res. 47 (2000) 219
4. Finlayson K., Turnbull L., January C.T., Sharkey J., and Kelly J.S. Eur. J. Pharmacol. 430 (2001) 147
5. Fermini B., and Fossa A.A. Annu. Rep. Med. Chem. 39 (2004) 323
6. Redfern W.S., Carlsson L., Davis A.S., Lynch W.G., Mackenzie I., Palethorpe S., Siegl P.K.S., Strang I., Sullivan A.T., Wallis R., Camm A.J., and Hammond T.G. Cardiovasc. Res. 58 (2003) 32
7. Keating M.T.K., and Sanguinetti M. Cell 104 (2001) 569
8. Clancy C.E., Kurokawa J., Tateyama M., Wehrens X.H.T., and Kass R.S. Annu. Rev. Pharmacol. Toxicol. 43 (2003) 441
9. Mitcheson J.S., Chen J., Lin M., Culberson C., and Sanguinetti M.C. Proc. Natl. Acad. Sci. U.S.A. 97 (2000) 12329
10. del Camino D., Holmgren M., Liu Y., and Yellen G. Nature 403 (2000) 321
11. Gralinski M.R. Toxicol. Pathol. 31 (2003) 11
12. Fossa A.A., Depasquale M.J., Raunig D.L., Avery M.J., and Leishman D.J. J. Pharmacol. Exp. Ther. 302 (2002) 828
13. Webster R., Allan G., Anto-Awuakye K., Harrison A., Kidd T., Leishman D., Phipps J., and Walker D. Xenobiotica 31 (2001) 633
14. Ghosh S., Elder A., Guo J., Mani U., Patane M., Carson K., Ye Q., Bennett R., Chi S., Jenkins T., Guan B., Kolbeck R., Smith S., Zhang C., LaRosa G., Jaffee B., Yang H., Eddy P., Lu C., Uttamsingh V., Horlick R., Harriman G., and Flynn D. J. Med. Chem. 49 (2006) 2669
15. Friesen R.W., Ducharme Y., Ball R.G., Blouin M., Boulet L., Cote B., Frenette R., Girard M., Guay D., Huang Z., Jones T.R., Laliberte F., Lynch J.J., Mancini J., Martins E., Masson P., Muise E., Pon D.J., Siegl P.K.S., Styhler A., Tsou N.N., Turner M.J., Young R.N., and Girard Y. J. Med. Chem. 46 (2003) 2413
16. Aslanian, R.; Piwinski, J. J.; Zhu, X.; Priestley, T.; Sorota, S.; Du, X.-Y.; McLeod, R. L.; West, R.; Williams, S. M.; Parra, L. E.; Hey, J. A. Books of Abstracts. In 225th National Meeting of the American Chemical Society, New Orleans, LA, March 23-27, 2003; American Chemical Society: Washington, DC, 2003; MEDI 238.
17. Ekin S., Crumb W.J., Sarazan R.D., Wikel J.H., and Wrighton S.A. J. Pharmacol. Exp. Ther. 301 (2002) 427
18. Cavalli A., Poluzzi E., De Ponti F., and Recanatini M. J. Med. Chem. 45 (2002) 3844
19. Recanatini M., Poluzzi E., Masetti M., Cavalli A., and De Ponti F. Med. Res. Rev. 25 (2005) 133
20. i) was calculated using the Cheng Prusoff equation (Biochem. Pharmacol. 1973, 22, 3099). Although this binding assay is relatively convenient to run for high throughput screening, it does not unanimously correlated with QT prolongation. For further verification of a compound's liability in QT prolongation, other functional assays such as patch clamp and Purkinje fiber electrophysiology assays should be performed.
21. Song Y., Clizbe L., Bhakta C., Teng W., Li W., Wu Y., Jia Z.J., Zhang P., Wang L., Doughan B., Su T., Kanter J., Woolfrey J., Wong P., Huang B., Tran K., Sinha U., Park G., Reed A., Malinowski J., Hollenbach S., Scarborough R.M., and Zhu B.-Y. Bioorg. Med. Chem. Lett. 12 (2002) 1511
22. Huang W., Zhang P., Zuckett J.F., Wang L., Woolfrey J., Song Y., Jia Z.J., Clizbe L.A., Su T., Tran K., Huang B., Wong P., Sinha U., Park G., Reed A., Malinowski J., Hollenbach S.J., Scarborough R.M., and Zhu B.-Y. Bioorg. Med. Chem. Lett. 13 (2003) 561
23. Woosley R.L., Chen Y., Freiman J.P., and Gillis R.A. J. Am. Med. Assoc. 269 (1993) 1532
24. Suessbrich H., Waldegger F., Lang F., and Busch A.E. FEBS Lett. 385 (1996) 77
25. Jean-Claude T. Am. J. Cardiol. 91 (2003) 41A
26. Roux B., and MacKinnon R. Science 285 (1999) 100
27. Suessbrich H., Schonherr R., Heinemann S.H., Lang F., and Busch A.E. FEBS Lett. 414 (1997) 435
28. Fenichel, R. R. .