PMID: 11901098Mar 20, 2002Paper

Regioselective metabolism of taxoids by human CYP3A4 and 2C8: structure-activity relationship

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Thierry CresteilFrançoise Gueritte

Abstract

Paclitaxel and docetaxel are metabolized by liver microsomal monooxygenases into inactive metabolites further eliminated from the body via the bile route. In spite of their close chemical structure, the two drugs are oxidized by two different enzymes; CYP2C8 catalyzes the 6-hydroxylation on the taxane ring of paclitaxel, whereas CYP3A4 oxidizes docetaxel on the tert-butyl group of the lateral chain in C13. Since paclitaxel and docetaxel differ only by two substitutions, the role of individual modifications was investigated; the regioselectivity of hydroxylation was assessed by high-pressure liquid chromatography/mass spectrometry, and enzymes implicated in individual reactions were identified using human liver microsomes and recombinant P450 expressed in Ad293 cells. The biotransformation of docetaxel, 10-deacetylpaclitaxel, and 10-deacetylbaccatin III was steadily increased (2- to 5-fold) by the addition of an acetyl group in position 10, suggesting that the presence of a hydrophobic group in position 10 stimulated hydroxylation by P450 proteins. The absence of the lateral chain at C13 in baccatin III severely impaired the metabolism supported by CYP3A4. The presence of a tert-butyl group in the lateral chain of docetaxel favo...Continue Reading

References

Feb 22, 1979·Nature·P B SchiffS B Horwitz
Feb 20, 1991·Journal of the National Cancer Institute·I Ringel, S B Horwitz
Mar 1, 1991·Journal of Medicinal Chemistry·F Guéritte-VoegeleinP Potier
Apr 14, 1982·Biochemical and Biophysical Research Communications·J ParnessS B Horwitz
Jan 1, 1995·Cancer Chemotherapy and Pharmacology·G KumarK Bhalla
Mar 7, 1998·European Journal of Biochemistry·M Sonnier, T Cresteil
Feb 10, 2000·Archives of Biochemistry and Biophysics·F RousselJ R Halpert
Sep 1, 2000·Bioorganic & Medicinal Chemistry·D GuénardF Guéritte

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Citations

May 9, 2012·Cancer Chemotherapy and Pharmacology·Toshitaka UchiyamaKayoko Saito
Jun 5, 2013·Biochemical Pharmacology·Pei H CuiMichael Murray
Jul 10, 2003·Lancet Neurology·Charles J VechtErik B Wilms
Dec 15, 2010·Pharmacogenetics and Genomics·Connie OshiroRuss Altman
Aug 22, 2013·Pharmacogenetics and Genomics·Christina L AquilanteTeri E Klein
Jun 23, 2012·Molecular Pharmacology·Shu-Yun ZhangJoyce A Goldstein
Dec 17, 2004·Journal of Clinical Pharmacology·Robert L WalskyR Scott Obach
Jul 17, 2004·Chemical & Pharmaceutical Bulletin·Toshimasa TanakaYoshio Yamamoto
Jul 28, 2011·Drug Metabolism and Pharmacokinetics·Luigi QuintieriMaura Floreani
Jan 20, 2005·Clinical Pharmacokinetics·Tony Antoniou, Alice L Tseng
Mar 25, 2006·Future Oncology·Dirk Schrijvers, Jan B Vermorken
Nov 4, 2005·Investigational New Drugs·Ron H N van Schaik
Sep 24, 2004·Gynecologic Oncology·Thomas ClouseMichael C Wiemann
Jun 12, 2009·Drug Metabolism Reviews·Shu-Feng ZhouBalram Chowbay
Jan 30, 2007·Expert Opinion on Pharmacotherapy·Sharon Marsh, Howard L McLeod
Aug 25, 2015·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Dipanjan PanGregory M Lanza
Apr 8, 2009·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Y-Y ZhangL Yang
Oct 3, 2009·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Y-Y ZhangL Yang
Aug 25, 2012·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Martin N FranssonHenrik Gréen
Jul 24, 2012·Journal of Inorganic Biochemistry·Francesco RuaGianfranco Gilardi
Jan 2, 2016·Pharmacological Reviews·Janne T BackmanPertti J Neuvonen
Aug 25, 2009·Toxicon : Official Journal of the International Society on Toxinology·Fujiang GuoKathleen S Rein
May 20, 2008·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Ron H N van Schaik
Jul 16, 2008·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Brett R JonesRoss A McKinnon
Dec 7, 2007·Cancer Letters·Kedar PurnapatreKulvinder Singh Saini
Jul 9, 2004·International Journal of Cancer. Journal International Du Cancer·Tomotaka TanakaMasahiko Nishiyama
Jun 6, 2006·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Miguel Angel IzquierdoJosep Ramón Germà-Lluch
Dec 6, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Ron H J Mathijssen, Ron H N van Schaik
Nov 27, 2014·Basic & Clinical Pharmacology & Toxicology·Yuji MukaiNobuo Inotsume
Feb 8, 2011·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Dong Kyun KimHye Suk Lee
Jul 24, 2015·The EPMA Journal·Keith Sacco, Godfrey Grech
Jun 25, 2008·Drug Metabolism and Pharmacokinetics·Rajinder SinghChin Eng Ong
Mar 19, 2013·Pharmacology & Therapeutics·Kelly Westbrook, Vered Stearns
Nov 9, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Martin N FranssonLena E Friberg
Feb 11, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Lin-Lin WangShu-Feng Zhou
Nov 28, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jiang-Wei ZhangLing Yang
Aug 12, 2004·The Journal of Pharmacology and Experimental Therapeutics·Thomas M PolasekJohn O Miners
Dec 3, 2003·European Journal of Anaesthesiology·S KvolikI Karner
Dec 17, 2003·The Journal of Biological Chemistry·Guillaume A SchochEric F Johnson
Mar 19, 2014·Anti-cancer Drugs·Vincent A de WegerJan H M Schellens
Feb 18, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hiroyuki HichiyaJun-ichi Sawada

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