{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T22:41:20Z","timestamp":1769121680047,"version":"3.49.0"},"reference-count":86,"publisher":"American Chemical Society (ACS)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Chem. Inf. Model."],"published-print":{"date-parts":[[2012,3,26]]},"DOI":"10.1021\/ci200523f","type":"journal-article","created":{"date-parts":[[2012,2,2]],"date-time":"2012-02-02T17:09:29Z","timestamp":1328202569000},"page":"686-695","source":"Crossref","is-referenced-by-count":9,"title":["A Pragmatic Approach Using First-Principle Methods to Address Site of Metabolism with Implications for Reactive Metabolite Formation"],"prefix":"10.1021","volume":"52","author":[{"given":"Ya-Wen","family":"Hsiao","sequence":"first","affiliation":[{"name":"AstraZeneca Research and Development S\u00f6dert\u00e4lje, SE-151 85 S\u00f6dert\u00e4lje, Sweden"}]},{"given":"Carl","family":"Petersson","sequence":"additional","affiliation":[{"name":"AstraZeneca Research and Development S\u00f6dert\u00e4lje, SE-151 85 S\u00f6dert\u00e4lje, Sweden"}]},{"given":"Mats A.","family":"Svensson","sequence":"additional","affiliation":[{"name":"AstraZeneca Research and Development S\u00f6dert\u00e4lje, SE-151 85 S\u00f6dert\u00e4lje, Sweden"}]},{"given":"Ulf","family":"Norinder","sequence":"additional","affiliation":[{"name":"AstraZeneca Research and Development S\u00f6dert\u00e4lje, SE-151 85 S\u00f6dert\u00e4lje, Sweden"},{"name":"Department of Pharmacy, Uppsala University, SE-751 23 Uppsala, Sweden"}]}],"member":"316","published-online":{"date-parts":[[2012,2,24]]},"reference":[{"key":"ref1\/cit1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.cbi.2010.11.002","volume":"192","author":"Thompson R. A.","year":"2011","journal-title":"Chem.-Biol. Interact."},{"key":"ref2\/cit2","doi-asserted-by":"crossref","first-page":"952","DOI":"10.2174\/138920008786485209","volume":"9","author":"Prakash C.","year":"2008","journal-title":"Curr. Drug. Metab."},{"key":"ref3\/cit3","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1146\/annurev-pharmtox-010510-100514","volume":"51","author":"Walsh J. S.","year":"2011","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref4\/cit4","doi-asserted-by":"crossref","first-page":"9019","DOI":"10.1021\/bi00449a010","volume":"28","author":"Korzekwa K. R.","year":"1989","journal-title":"Biochemistry"},{"key":"ref5\/cit5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1124\/dmd.30.1.7","volume":"30","author":"Jones J. P.","year":"2002","journal-title":"Drug Metab. Dispos."},{"key":"ref6\/cit6","doi-asserted-by":"crossref","first-page":"2998","DOI":"10.1039\/B410729B","volume":"2","author":"Bathelt C. M.","year":"2004","journal-title":"Org. Biomol. Chem."},{"key":"ref7\/cit7","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1517\/17425255.2011.553599","volume":"7","author":"Tarcsay \u00c1.","year":"2011","journal-title":"Expert. Opin. Metab. Toxicol."},{"key":"ref8\/cit8","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1126\/science.117.3039.340","volume":"117","author":"Leffler J. E.","year":"1953","journal-title":"Science"},{"key":"ref9\/cit9","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1021\/ja01607a027","volume":"77","author":"Hammond G. S.","year":"1955","journal-title":"J. Am. Chem. Soc."},{"key":"ref10\/cit10","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1002\/cmdc.200900363","volume":"4","author":"Rydberg P.","year":"2009","journal-title":"Chem. Med. Chem."},{"key":"ref11\/cit11","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/0022-2836(71)90324-X","volume":"55","author":"Lee B.","year":"1971","journal-title":"J. Mol. Biol."},{"key":"ref12\/cit12","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1107\/S0907444994003112","volume":"50","year":"1994","journal-title":"Acta Cryst. D"},{"key":"ref13\/cit13","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1002\/1099-0682(200012)2000:12<2455::AID-EJIC2455>3.0.CO;2-4","volume":"12","author":"Ogliaro F.","year":"2000","journal-title":"Eur. J. Inorg. Chem."},{"key":"ref14\/cit14","doi-asserted-by":"crossref","first-page":"6489","DOI":"10.1021\/jm060551l","volume":"49","author":"Olsen L.","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref15\/cit15","doi-asserted-by":"crossref","first-page":"13058","DOI":"10.1021\/jp803854v","volume":"112","author":"Rydberg P.","year":"2008","journal-title":"J. Phys. Chem. A"},{"key":"ref16\/cit16","unstructured":"Frisch, J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, \u00d6.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J.Gaussian 09, revision A.1;Gaussian Inc.:Wallingford, CT, 2009."},{"key":"ref17\/cit17","doi-asserted-by":"crossref","first-page":"5648","DOI":"10.1063\/1.464913","volume":"98","author":"Becke A. D.","year":"1993","journal-title":"J. Chem. Phys."},{"key":"ref18\/cit18","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1103\/PhysRevB.37.785","volume":"37","author":"Lee C.","year":"1988","journal-title":"Phys. Rev. B"},{"key":"ref19\/cit19","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1063\/1.1677527","volume":"56","author":"Hehre W. J.","year":"1972","journal-title":"J. Chem. Phys."},{"key":"ref20\/cit20","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/BF00533485","volume":"28","author":"Hariharan P. C.","year":"1973","journal-title":"Theor. Chem. Acc."},{"key":"ref21\/cit21","doi-asserted-by":"crossref","first-page":"3654","DOI":"10.1063\/1.444267","volume":"77","author":"Francl M. M.","year":"1982","journal-title":"J. Chem. Phys."},{"key":"ref22\/cit22","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1021\/cr9904009","volume":"105","author":"Tomasi J.","year":"2005","journal-title":"Chem. Rev."},{"key":"ref23\/cit23","doi-asserted-by":"crossref","first-page":"13149","DOI":"10.1021\/jp8016908","volume":"112","author":"Bathelt C. M.","year":"2008","journal-title":"J. Phys. Chem. A"},{"key":"ref24\/cit24","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1021\/cr0307143","volume":"105","author":"Denisov I.","year":"2005","journal-title":"Chem. Rev."},{"key":"ref25\/cit25","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1126\/science.157.3796.1524","volume":"157","author":"Guroff G.","year":"1967","journal-title":"Science"},{"key":"ref26\/cit26","doi-asserted-by":"crossref","first-page":"6525","DOI":"10.1021\/ja01025a058","volume":"90","author":"Jerina D. M.","year":"1968","journal-title":"J. Am. Chem. Soc."},{"key":"ref27\/cit27","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1124\/dmd.105.006866","volume":"33","author":"Bu H.","year":"2005","journal-title":"Drug Metab. Dispos."},{"key":"ref28\/cit28","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1124\/dmd.105.004341","volume":"34","author":"Chen Q.","year":"2006","journal-title":"Drug Metab. Dispos."},{"key":"ref29\/cit29","doi-asserted-by":"crossref","first-page":"535","DOI":"10.3109\/00498259109039493","volume":"21","author":"Zheng J.","year":"1991","journal-title":"Xenobiotica"},{"key":"ref30\/cit30","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.3109\/00498258909043177","volume":"19","author":"Koch P.","year":"1989","journal-title":"Xenobiotica"},{"key":"ref31\/cit31","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1021\/tx020063q","volume":"15","author":"Mutlib A.","year":"2002","journal-title":"Chem. Res. Toxicol."},{"key":"ref32\/cit32","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1021\/tx990023v","volume":"12","author":"Watt K.","year":"1999","journal-title":"Chem. Res. Toxicol."},{"key":"ref33\/cit33","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.bbrc.2005.08.091","volume":"338","author":"Dansette P. M.","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref34\/cit34","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1124\/dmd.106.011940","volume":"35","author":"Mannens G. S. J.","year":"2007","journal-title":"Drug Metab. Dispos."},{"key":"ref35\/cit35","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1124\/dmd.106.012336","volume":"35","author":"Mamidi R. N. V. S.","year":"2007","journal-title":"Drug Metab. Dispos."},{"key":"ref36\/cit36","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1124\/dmd.109.031344","volume":"38","author":"Wong S. G.","year":"2010","journal-title":"Drug Metab. Dispos."},{"key":"ref37\/cit37","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1021\/tx025635l","volume":"16","author":"Singh R.","year":"2003","journal-title":"Chem. Res. Toxicol."},{"key":"ref38\/cit38","first-page":"638","volume":"29","author":"Yergey J. A.","year":"2001","journal-title":"Drug Metab. Dispos."},{"key":"ref39\/cit39","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1021\/tx9003243","volume":"23","author":"Chen H.","year":"2010","journal-title":"Chem. Res. Toxicol."},{"key":"ref40\/cit40","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1021\/tx960060b","volume":"9","author":"SahaliSahly Y.","year":"1996","journal-title":"Chem. Res. Toxicol."},{"key":"ref41\/cit41","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1124\/jpet.107.125302","volume":"322","author":"Williams D. P.","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref42\/cit42","first-page":"1318","volume":"25","author":"Born S. L.","year":"1997","journal-title":"Drug Metab. Dispos."},{"key":"ref43\/cit43","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1124\/dmd.30.5.483","volume":"30","author":"Born S. L.","year":"2002","journal-title":"Drug Metab. Dispos."},{"key":"ref44\/cit44","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1124\/dmd.104.000240","volume":"32","author":"Reddy V.","year":"2004","journal-title":"Drug Metab. Dispos."},{"key":"ref45\/cit45","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1124\/dmd.109.028910","volume":"38","author":"Zhuo X.","year":"2010","journal-title":"Drug Metab. Dispos."},{"key":"ref46\/cit46","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1021\/tx0101191","volume":"15","author":"Mutlib A. E.","year":"2002","journal-title":"Chem. Res. Toxicol."},{"key":"ref47\/cit47","first-page":"663","volume":"25","author":"Kitani M.","year":"1997","journal-title":"Drug Metab. Dispos."},{"key":"ref48\/cit48","doi-asserted-by":"crossref","first-page":"13184","DOI":"10.1021\/bi981198r","volume":"37","author":"Koenigs L. L.","year":"1998","journal-title":"Biochemistry"},{"key":"ref49\/cit49","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.1021\/bi00612a033","volume":"17","author":"McCormick A. M.","year":"1978","journal-title":"Biochemistry"},{"key":"ref50\/cit50","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1021\/tx010153f","volume":"15","author":"Chen H.","year":"2002","journal-title":"Chem. Res. Toxicol."},{"key":"ref51\/cit51","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1021\/tx000029g","volume":"13","author":"Mutlib A.","year":"2000","journal-title":"Chem. Res. Toxicol."},{"key":"ref52\/cit52","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/S0090-9556(25)06761-3","volume":"23","author":"Machinist J. M.","year":"1995","journal-title":"Drug Metab. Dispos."},{"key":"ref53\/cit53","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/S0022-3565(25)20538-9","volume":"259","author":"Turgeon J.","year":"1991","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref54\/cit54","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1046\/j.1365-2125.1998.00048.x","volume":"46","author":"Nakajima M.","year":"1998","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref55\/cit55","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/S0022-3565(25)23210-4","volume":"255","author":"Imaoka S.","year":"1990","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref56\/cit56","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1592\/phco.20.3.182.34775","volume":"20","author":"Matzke G.","year":"2000","journal-title":"Pharmacotherapy"},{"key":"ref57\/cit57","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S0009-9236(96)90001-6","volume":"59","author":"Engel G.","year":"1996","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref58\/cit58","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/j.1472-8206.1998.tb00946.x","volume":"12","author":"Coulet M.","year":"1998","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref59\/cit59","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0022-3565(24)36731-X","volume":"281","author":"Koyama E.","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref60\/cit60","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/S0090-9556(25)07392-1","volume":"24","author":"Ching M. S.","year":"1996","journal-title":"Drug Metab. Dispos."},{"key":"ref61\/cit61","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/S0090-9556(25)08435-1","volume":"22","author":"Masubuchi Y.","year":"1994","journal-title":"Drug Metab. Dispos."},{"key":"ref62\/cit62","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1248\/bpb.19.1511","volume":"19","author":"Kariya S.","year":"1996","journal-title":"Biol. Pharmacol. Bull."},{"key":"ref63\/cit63","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/S0090-9556(24)15074-X","volume":"28","author":"Thijssen H.","year":"2000","journal-title":"Drug Metab. Dispos."},{"key":"ref64\/cit64","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1124\/dmd.104.002410","volume":"33","author":"Ma X. C.","year":"2005","journal-title":"Drug Metab. Dispos."},{"key":"ref65\/cit65","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1016\/S0090-9556(24)14929-X","volume":"27","author":"Shimada T.","year":"1999","journal-title":"Drug Metab. Dispos."},{"key":"ref66\/cit66","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1093\/bja\/80.6.788","volume":"80","author":"Guitton J.","year":"1998","journal-title":"Brit. J. Anaesth."},{"key":"ref67\/cit67","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1080\/00498250050200159","volume":"30","author":"Ozawa S.","year":"2000","journal-title":"Xenobiotica"},{"key":"ref68\/cit68","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1124\/dmd.30.2.103","volume":"30","author":"Otake Y.","year":"2002","journal-title":"Drug Metab. Dispos."},{"key":"ref69\/cit69","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1046\/j.1365-2125.1999.00005.x","volume":"48","author":"Coller J. K.","year":"1999","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref70\/cit70","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1021\/tx00025a009","volume":"5","author":"Rettie A. E.","year":"1992","journal-title":"Chem. Res. Toxicol."},{"key":"ref71\/cit71","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/S0090-9556(25)06865-5","volume":"23","author":"Zhang Z.","year":"1995","journal-title":"Drug Metab. Dispos."},{"key":"ref72\/cit72","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/S0090-9556(25)07489-6","volume":"24","author":"Ekstr\u00f6m G.","year":"1996","journal-title":"Drug Metab. Dispos."},{"key":"ref73\/cit73","first-page":"840","volume":"25","author":"Bloomer J.","year":"1997","journal-title":"Drug Metab. Dispos."},{"key":"ref74\/cit74","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/0006-2952(95)00048-5","volume":"49","author":"Tracy T. S.","year":"1995","journal-title":"Biochem. Pharmacol."},{"issue":"2","key":"ref75\/cit75","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/0003-9861(91)90315-A","volume":"284","author":"Liu G.","year":"1991","journal-title":"Arch. Biochem. Biophys."},{"key":"ref76\/cit76","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/S0026-895X(25)09739-1","volume":"46","author":"Yamazaki H.","year":"1994","journal-title":"Mol. Pharmacol."},{"key":"ref77\/cit77","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/S0022-3565(24)37072-7","volume":"283","author":"Yamazaki H.","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref78\/cit78","first-page":"970","volume":"25","author":"Oldham H. G.","year":"1997","journal-title":"Drug Metab. Dispos."},{"key":"ref79\/cit79","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1111\/j.1742-4658.2006.05235.x","volume":"273","author":"Kim K.","year":"2006","journal-title":"FEBS J."},{"key":"ref80\/cit80","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/S0090-9556(25)06731-5","volume":"23","author":"Spaldin V.","year":"1995","journal-title":"Drug Metab. Dispos."},{"key":"ref81\/cit81","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1365-2125.2004.02156.x","volume":"58","author":"Ward B. A.","year":"2004","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref82\/cit82","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1002\/ijc.21665","volume":"118","author":"He X.","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref83\/cit83","doi-asserted-by":"crossref","first-page":"14264","DOI":"10.1021\/bi991195u","volume":"38","author":"Mancy A.","year":"1999","journal-title":"Biochemistry"},{"key":"ref84\/cit84","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/S0006-2952(99)00167-7","volume":"58","author":"Bort R.","year":"1999","journal-title":"Biochem. Pharmacol."},{"key":"ref85\/cit85","doi-asserted-by":"crossref","first-page":"10365","DOI":"10.1021\/bi00033a007","volume":"34","author":"Mancy A.","year":"1995","journal-title":"Biochemistry"},{"key":"ref86\/cit86","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1124\/dmd.108.023358","volume":"37","author":"Hutzler J. M.","year":"2009","journal-title":"Drug Metab. Dispos."}],"container-title":["Journal of Chemical Information and Modeling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/ci200523f","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T19:18:49Z","timestamp":1742411929000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/doi\/10.1021\/ci200523f"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,24]]},"references-count":86,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2012,3,26]]}},"alternative-id":["10.1021\/ci200523f"],"URL":"https:\/\/doi.org\/10.1021\/ci200523f","relation":{},"ISSN":["1549-9596","1549-960X"],"issn-type":[{"value":"1549-9596","type":"print"},{"value":"1549-960X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,24]]}}}