Structure-activity relationship (SAR): Effort towards blocking N-glucuronidation of indazoles (PF-03376056) by human UGT1A enzymes

Drug Metabolism Letters

Volumn 3, Issue 1, 2009, Pages 28-34

  Rose, Kelly ^a   Yang, Young Sun ^b   Sciotti, Richard ^c   Cai, Hongliang ^b  

^a PFIZER INC   (United States)

^b PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

^c PGRD   (United States)

Author keywords

Indazoles; N glucuronidation; UGT1A

Indexed keywords

GLUCURONOSYLTRANSFERASE 1A1; INDAZOLE DERIVATIVE; PF 03376056; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CATALYSIS; CONTROLLED STUDY; DRUG CLEARANCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG METABOLISM; DRUG STRUCTURE; ELECTRON; GLUCURONIDATION; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LIVER CELL; MALE; MASS SPECTROMETRY; MOUSE; NONHUMAN; PERITONITIS; PRIORITY JOURNAL; RAT; SEPSIS; STRUCTURE ACTIVITY RELATION;

ANIMALS; AZETIDINES; BACTERIA; BILE DUCTS; ENZYME INHIBITORS; GLUCURONIDES; GLUCURONOSYLTRANSFERASE; HEPATOCYTES; INDAZOLES; MALE; PERITONITIS; RATS; RATS, SPRAGUE-DAWLEY; RECOMBINANT PROTEINS; SEPSIS; STRUCTURE-ACTIVITY RELATIONSHIP;

BACTERIA (MICROORGANISMS); MURINAE; RATTUS;

EID: 66149129211     PISSN: 18723128     EISSN: None     Source Type: Journal    
DOI: 10.2174/187231209787176371     Document Type: Article

References (19)

1. Classen, S.; Olland, S.; and Berger, J.M. Structure of the topoisomerase II ATPase region and its mechanism of inhibition by the chemotherapeutic agent ICRF-187. Proc. Natl. Acad. Sci. USA, 2003, 100, 10629.
2. Maxwell, A. and Lawson, D.M. The ATP-binding site of type II topoisomerases as a target for antibacterial drugs. Curr. Top. Med. Chem., 2003, 3, 283.
3. Van de Waterbeemd, H. and Gifford, E. ADMET in silico modeling: towards prediction paradise? Nat. Rev. Drug Discov., 2003, 2, 192.
4. Miners, J.O.; Smith, P.A.; Sorich, M.J.; McKinnon, R.A. and Mackenzier, P.I. Predicting human drug glucuronidation parameters: application of in vitro and in silico modeling approaches. Annu. Rev. Pharmacol. Toxicol., 2004, 44, 1.
5. Smith, P.A.; Sorich, M.J.; Low, L.S.C.; McKinnon, R.A. and Miners, J.O. Towards integrated ADME prediction: past, present, and future directions for modeling metabolism by UDP-glucuronosyltransferases. J. Mol. Graph. Model., 2004, 22, 507.
6. Reddy, A.; Heimbach, T.; Freiwald, S.; Smith, D.; Winters, R.; Michael, S.; Surendran, N. and Cai, H. Validation of an automated human hepatocyte assay for the determination and prediction of intrinsic clearance in discovery. J. Pharm. Biomed. Anal., 2005, 37, 319.
7. Guengerich, F.P. Cytochrome P450s and other enzymes in drug metabolism and toxicity. AAPS J., 2006, 8, E101.
8. Radominska-Pandya, A.; Czernik, P.J.; Little, J.M.; Battaglia, E. and Mackenzie, P.I. Structural and functional studies of UDP-glucuronosyltransferases. Drug Metab. Rev., 1999, 31, 817.
9. Mackenzie, P.I.; Owens, I.S.; Burchell, B.; Bock, K.W.; Bairoch, A. and Belanger, A. The UDP-glycosyltransferase gene superfamily-recommended nomenclature update based on evolutionary divergence. Pharmacogenetics, 1997, 7, 255.
10. King, C.D.; Rios, G.R.; Green, M.D. and Tephly, T.R. UDP-glucuronosyltransferases. Curr. Drug Metab., 2000, 1, 143.
11. Radominska-Pandya, A.; Bratton, S. and Little, J.M. A historical overview of the heterologous expression of mammalian UDP-glucuronosyltransferase isoforms over the past twenty years. Curr. Drug Metabol., 2005, 6, 141.
12. Tukey, R.H. and Strassburg, C.P. Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Ann. Rev. Pharmacol. Toxicol., 2000, 40, 581.
13. Lewis, D.F.V.; Modi, S. and Dickins, M. Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab. Rev., 2002, 34, 69.
14. Lewis, D.F.V.; Lake, B.G. and Dickins, M. Quantitative structureactivity relationships (QSARs) in inhibitors of various cytochromes P450: the importance of compound lipophilicity. J. Enzyme Inhib. Med. Chem., 2007, 22, 1.
15. Bichlmaiero, I.; Finel, M.; Sippl, W. and Kauhaluoma, J.Y. Stereochemical and steric control of the UDP-glucuronosyltransferasecatalyzed conjugation reaction: a rational approach for the design of inhibitors for the human UGT2B7. Chem. Med. Chem., 2007, 6, 1730.
16. Kamaldeep, K.C.; Stuart, W.P. and Nigel, J.W. Quantitative structure activity relationships in drug metabolism. Curr. Top. Med. Chem., 2006, 6, 1569.
17. Mimoto, T.; Terashima, K.; Nojima, S.; Takaku, H.; Nakayama, M.; Shintani, M.; Yamaoka, T. and Hayashi, H. Structure-activity and structure-metabolism relationships of HIV protease inhibitors containing the 3-hydroxy-2 methylbenzoylallophenylnorstatine structure. Bioorg. Med. Chem., 2004, 12, 281.
18. Smith, P.A.; Sorich, M.J.; Mckinnon, R.A. and Miners, J.O. Pharmacophore and quantitative structure-activity relationship modeling: complementary approaches for the rationalization and prediction of UDP-glucuronosyltransferase 1A4 substrate specificity. J. Med. Chem., 2003, 46, 1617.
19. Strassburg, C.P.; Oldhafer, K; Manns, M.P. and Tukey, R.H. Differential expression of the UGT1A Locus in human liver, biliary, and gastric tissue: identification of UGT1A7 and UGT1A10 transcripts in extrahepatic tissue. Mol. Pharmacol., 1997, 52, 212.