Bioactivation of isothiazoles: Minimizing the risk of potential toxicity in drug discovery

Chemical Research in Toxicology

Volumn 23, Issue 11, 2010, Pages 1743-1752

  Teffera, Yohannes ^a   Choquette, Deborah ^a   Liu, Jingzhou ^a   Colletti, Adria E ^a   Hollis, L Steven ^a   Lin, Min Hwa Jasmine ^a   Zhao, Zhiyang ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

7 (2 METHOXYETHOXY) N ((6 (3 METHYL 5 ISOTHIAZOLYL)[1,2,4]TRIAZOLO[4,3 B]PYRIDAZIN 3 YL)METHYL) 1,5 NAPHTHYRIDIN 4 AMINE; 7 METHOXY N ((6 (3 METHYLISOTHIAZOL 5 YL) [1,2,4]TRIAZOLO[4,3 B]PYRIDAZIN 3 YL)METHYL)1,5 NAPHTHYRIDIN 4 AMINE; CYTOCHROME P450; CYTOCHROME P450 1A2; CYTOCHROME P450 2A2; CYTOCHROME P450 2D6; CYTOCHROME P450 3A1; CYTOCHROME P450 3A2; CYTOCHROME P450 3A4; GLUTATHIONE; ISOTHIAZOLE DERIVATIVE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CHEMICAL REACTION; CONJUGATION; CONTROLLED STUDY; COVALENT BOND; DOG; DRUG MECHANISM; DRUG POTENCY; ENZYME ACTIVATION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; INCUBATION TIME; LIVER MICROSOME; MALE; MASS SPECTROMETRY; MICROSOME; MONKEY; MOUSE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; OXIDATION; PROTEIN BINDING; RAT; RISK FACTOR; SPECIES DIFFERENCE;

ANIMALS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CYTOCHROME P-450 ENZYME SYSTEM; DOGS; DRUG EVALUATION, PRECLINICAL; GLUTATHIONE; HUMANS; MAGNETIC RESONANCE SPECTROSCOPY; MICE; MICROSOMES, LIVER; MOLECULAR CONFORMATION; NAPHTHYRIDINES; PROTEIN BINDING; PYRIDAZINES; RATS; RISK FACTORS; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; THIAZOLES;

CANIS FAMILIARIS; MUS; RATTUS;

EID: 78649306254     PISSN: 0893228X     EISSN: 15205010     Source Type: Journal    
DOI: 10.1021/tx100208k     Document Type: Article

References (21)

1. Baillie, T. A. and Kassahun, K. (2001) Biological reactive intermediates in drug discovery and development: a perspective from the pharmaceutical industry Adv. Exp. Med. Biol. 500, 45-51
2. Naisbitt, D. J., Williams, D. P., Pirmohamed, M., Kitteringham, N. R., and Park, B. K. (2001) Reactive metabolites and their role in drug reactions Curr. Opin. Allergy. Clin. Immunol. 1, 317-325
3. Park, B. K., Naisbitt, D. J., Gordon, S. F., Kitteringham, N. R., and Pirmohamed, M. (2001) Metabolic activation in drug allergies Toxicology 158, 11-23
4. Uetrecht, J. (2001) Prediction of a new drug's potential to cause idiosyncratic reactions Curr. Opin. Drug Discovery Dev. 4, 55-59
5. Knowles, S. R., Uetrecht, J., and Shear, N. H. (2000) Idiosyncratic drug reactions: the reactive metabolite syndromes Lancet 356, 1587-1591
6. Hess, D. A. and Rieder, M. J. (1997) The role of reactive drug metabolites in immune-mediated adverse drug reactions Ann. Pharmacother. 31, 1378-1387
7. Nelson, S. D. (1995) Mechanisms of the formation and disposition of reactive metabolites that can cause acute liver injury Drug Metab. Rev. 27, 147-177
8. Hinson, J. A., Pumford, N. R., and Nelson, S. D. (1994) The role of metabolic activation in drug toxicity Drug Metab. Rev. 26, 395-412
9. Evans, D. C., Watt, A. P., Nicoll-Griffith, D. A., and Baillie, T. A. (2004) Drug-protein adducts: an industry perspective on minimizing the potential for drug bioactivation in drug discovery and development Chem. Res. Toxicol. 17, 3-16
10. Baillie, T. A. and Davis, M. R. (1993) Mass spectrometry in the analysis of glutathione conjugates Biol. Mass. Spectrom. 22, 319-325
11. Kalgutkar, A. S. and Soglia, J. R. (2005) Minimising the potential for metabolic activation in drug discovery Expert Opin. Drug Metab. Toxicol. 1 (1) 91-142
12. Kalgutkar, A. S., Gardner, I., Obach, R. S., Shaffer, C. L., Callegari, E., Henne, K. R., Mutlib, A. E., Dalvie, D. K., Lee, J. S., Nakai, Y., O'Donnell, J. P., Boer, J., and Harriman, S. P. (2005) A comprehensive listing of bioactivation pathways of organic functional groups Curr. Drug Metab. 6 (3) 161-225
13. Schmid, J., Busch, U., Trummlitz, G., Prox, A., Kaschke, S., and Wachsmuth, H. (1995) Meloxicam: metabolic profile and biotransformation products in the rat Xenobiotica 25, 1219-1236
14. Boezio, A. A., Berry, L., Albrecht, B. K., Bauer, D., Bellon, S. F., Bode, C., Chen, A., Choquette, D., Dussault, I., Hirai, S., Kaplan-Lefko, P., Larrow, J. F., Lin, M. H., Lohman, J., Potashman, M. H., Rex, K., Santostefano, M., Shah, K., Shimanovich, R., Springer, S. K., Teffera, Y., Yang, Y., Zhang, Y., and Harmange, J. C. (2009) Discovery and optimization of potent and selective triazolopyridazine series of c-Met inhibitors Bioorg. Medicinal Chem. Lett. 19 (22) 6307-6312
15. Albrecht, B. K., Bauer, D., Bellon, S. F., Bode, C., Booker, S., Boezio, A. A., Choquette, D., D'Amico, D., Harmange, J. C., Hirai, S., Hungate, R. W., Kim, T. S., Lewis, R., Liu, L., Lohman, J., Norman, M., Potashman, M. H., Siegmund, A., Springer, S., Stec, M., Xi, N., and Yang, K. (2009) Fused Heterocyclic Derivatives and Methods of Use, U.S. Pat. Appl. 20090124612, May 14, 2009.
16. Day, S. H., Mao, A., White, R., Schulz-Utermoehl, T., Miller, R., and Beconi, M. G. (2005) A semi-automated method for measuring the potential for protein covalent binding in drug discovery J. Pharmacol. Toxicol Methods 52, 278-285
17. Mizutani, T., Yoshida, K., and Kawazoe, S. (1994) Formation of toxic metabolites from thiabendazole and other thiazoles in mice. Identification of thioamides as ring cleavage products Drug Metab. Dispos. 22, 750-755
18. Mizutani, T. and Suzuki, K. (1996) Relative hepatotoxicity of 2-(substituted phenyl)thiazoles and substituted thiobenzamides in mice: evidence for the involvement of thiobenzamides as ring cleavage metabolites in the hepatotoxicity of 2-phenylthiazoles Toxicol. Lett. 85, 101-105
19. Mizutani, T., Yoshida, K., and Ito, K. (1992) Nephrotoxicity of thiazoles structurally related to thiabendazole in mice depleted of glutathione by treatment with buthionine sulfoximine Res. Commun. Chem. Pathol. Pharmacol. 75, 29-38
20. Dalvie, D. K., Kalgutar, A. S., Khojasteh-Bakht, S. C., Obach, R. S., and O'Donnel, J. P. (2002) Biotransformation reactions of five-membered aromatic heterocyclic rings Chem. Res. Toxicol. 15 (3) 269-299
21. Trimble, L. A., Chauret, N., Silva, J. M., Nicoll-Griffith, D. A., Li, C.-S., and Yergey, J. A. (1997) Characterization of the in vitro oxidative metabolites of the COX-2 selective inhibitor L-766,112 Bioorg. Med. Chem. Lett. 7, 53-56