In vitro and in vivo metabolism of a gamma-secretase inhibitor BMS-299897 and generation of active metabolites in milligram quantities with a microbial bioreactor

Current Drug Metabolism

Volumn 7, Issue 8, 2006, Pages 883-896

  Zhang, Donglu ^a   Hanson, Ronald ^a   Roongta, Vikram ^a   Dischino, Douglas D ^a   Gao, Qi ^a   Sloan, Charles P ^a   Polson, Craig ^a   Keavy, Daniel ^a   Zheng, Ming ^a   Mitroka, James ^a   Yeola, Suresh ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

Acyl glucuronides; Fungal biotransformation; Hepatocytes; Mass spectrometry; Metabolism; Microbial bioreactor; Microsomes; Oxidative metabolites

Indexed keywords

4 [2 [1 [4 CHLORO N (2,5 DIFLUOROPHENYL)PHENYLSULFONAMIDO]ETHYL] 5 FLUORPHENYL]BUTANOIC ACID; BENZENE DERIVATIVE; BMS 299897; BMS 471103; BMS 471104; CARBON 14; DRUG METABOLITE; GAMMA SECRETASE; GAMMA SECRETASE INHIBITOR; GLUCURONIDE; HYDROXYL GROUP; LACTONE;

ANIMAL CELL; ANIMAL EXPERIMENT; BILE DUCT; BILE LEVEL; BIOREACTOR; CANNULATION; CONTROLLED STUDY; CULTURE TECHNIQUE; CUNNINGHAMELLA; DOG; DRUG CONJUGATION; DRUG HYDROXYLATION; DRUG METABOLISM; DRUG SCREENING; DRUG STRUCTURE; DRUG TRANSFORMATION; ENZYME INHIBITION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; ISOMERISM; LIQUID CHROMATOGRAPHY; LIVER CELL; LIVER MICROSOME; MALE; MONKEY; NONHUMAN; OXIDATION; PROCESS DEVELOPMENT; RADIOACTIVITY; RAT; REVIEW; SAMPLE SIZE; SINGLE DRUG DOSE; STEREOCHEMISTRY; STEREOISOMERISM; STRUCTURE ANALYSIS; TANDEM MASS SPECTROMETRY; TOXICITY TESTING; X RAY ANALYSIS;

AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; BILE; BIOREACTORS; BIOTRANSFORMATION; BUTYRIC ACIDS; CARBON RADIOISOTOPES; CELL LINE, TUMOR; CELLS, CULTURED; CUNNINGHAMELLA; DOGS; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; GLUCURONIDES; HEPATOCYTES; HUMANS; HYDROCARBONS, HALOGENATED; MACACA FASCICULARIS; MALE; MICROSOMES, LIVER; RATS; RATS, SPRAGUE-DAWLEY;

EID: 33845313935     PISSN: 13892002     EISSN: None     Source Type: Journal    
DOI: 10.2174/138920006779010566     Document Type: Review

References (24)

1. Hardy, J. A.; Higgins, G. A. (1992) Science, 256, 184-185.
2. Selkoe, D. J. (1994) Annu. Rev. Cell Biol., 10, 373-403.
3. Hardy, J. (1997) Trends Neurosci., 20, 154-159.
4. Seubert, P.; Vigo-Pelfrey, C.; Esch, F.; Lee, M.; Dovey, H.; Davis, D.; Sinha, S.; Schiossmacher, M.; Whaley, J.; Swindlehurst, C.; McCormack, R.; Wolfert, R.; Selkoe, D.; Lieberburg. I.; Schenk, D. (1992) Nature, 359, 325-327.
5. Dovey, H. F.; John, V.; Anderson, J. P.; Chen, L. Z.; Saint Andrieu, P.; Fang, Y. (2001), J. Neurochem., 76, 173-181.
6. Smith, D. W.; Munoz, B.; Srinivasan, K.; Bergstrom, C. P.; Chaturvedula, P. V.; Deshpande, M. S.; Keavy, D. J.; Lau, W. Y.; Parker, M. F.; Sloan, C. P.; Wallace, O. B.; Wang, H. H. (2000) WO 2000050391.
7. Anderson, J. J.; Holtz, G.; Baskin, P. P.; Turner, M.; Rowe, B.; Wang, B.; Kounnas, M. Z.; Lamb, B. T.; Barten, D.; Felsenstein, K.; McDonald, I.; Srinivasan, K.; Munoz, B.; Wagner, S. L. (2005) Biochem. Pharmacol., 69, 689-698.
8. Lin, J. H.; Lu, A.Y.H. (1997) Pharmacol. Rev., 49, 403-449.
9. Zhang, D.; Evans, F. E.; Freeman, J. P.; Duhart, Jr. B.; Cerniglia, C. E. (1995) Drug Metab. Dispos., 23, 1417-1425.
10. Rao, G. A.; Davis, P. J. (1997) Drug Metab. Dispos., 25, 709-715.
11. Schlenk, D.; Bevers, R. J.; Vertino, A. M.; Cerniglia, C. E. (1994) Xenobiotica, 24, 1077-1083.
12. Zhang, D.; Evans, F. E.; Freeman, J. P.; Yang, Y.; Deck, J.; Cerniglia, C. E. (1996) Chem.-Biol. Interac., 102, 79-92.
13. Smith, R. V.; Rosazza, J. P. (1982) In Microbial Transformations of Bioactive Compounds, CRC Press, Inc., Boca Raton, FL, vl.I pp. 1-42.
14. Rosazza, J. P.; Smith, R. V. (1979) Adv. Appl. Microbiol., 25, 169-203.
15. Davis, P. J.; Yang, W.; Hezari M.; Campos, J.; Reddy, C. G (1992) In Proceedings of the ACS Symposium, Biosynthesis and Metabolism of Secondary Metabolite and Natural Products (R. J. Petroski, ed.), Plenum Publishing, New York, pp. 197-208.
16. Abourashed, E. A.; Hufford, C. D. (1996) J. Nat. Prod., 59, 251-253.
17. Cheng, Y. C.; Prusoff, W. H. (1973) Biochem. Pharma., 22, 3099-3109.
18. Seikikawa, H.; Yagi, N.; Lin, E. T.; Benet, L. Z. (1995) Biol. Pharm. Bull., 18, 134-139.
19. Ding, A.; Zia-Amirhossoini, P.; MaDonagh, A.F.; Burlingame, A. L.; Benet, L. Z. (1995) Drug Metab. Dispos., 23, 369.
20. Duhart, B., Zhang, D. L., Deck, J.; Freeman, J. P.; Cerniglia, C. E. (1999) Xenobiotica, 29, 733-746.
21. Zhang, D. L.; Yang, Y.; Castlebury, L. A.; Cerniglia, C. E. (1996) FEMS Microbiol. Lett., 145, 261-265.
22. Rushmore, T. H.; Reider, P. J.; Slaughter, D.; Assang, C.; Shou, M. (2000) Metab. Eng., 2, 115-125.
23. Akira, K.; Uchijima, T.; Hashimoto, T. (2002) Chem. Res. Toxicol., 15, 765-772.
24. Mortensen, R. W.; Corcoran, O.; Cornett, C.; Sidelmann, U. G.; Lindon, J. C.; Nicholson, J. K.; Hansen, S. T. (2001) Drug Metab.. Dispos., 29, 375-380.