Ticlopidine as a selective mechanism-based inhibitor of human cytochrome P450 2C19.
- N. Ha-Duong, S. Dijols, A. Macherey, J. Goldstein, P. Dansette, D. Mansuy
- Biology, ChemistryBiochemistry
- 15 September 2001
Ticlopidine is the first selective mechanism-based inhibitor of human liver CYP2C19 and should be a new interesting tool for studying the topology of the active site of CYP 2C19.
Determinants of Cytochrome P450 2C8 Substrate Binding
- G. Schoch, J. Yano, S. Sansen, P. Dansette, C. Stout, Eric F. Johnson
- Chemistry, BiologyJournal of Biological Chemistry
- 20 June 2008
Although a crystal structure and a pharmacophore model are available for cytochrome P450 2C8, the role of protein flexibility and specific ligand-protein interactions that govern substrate binding…
Structure of mammalian cytochrome P450 2C5 complexed with diclofenac at 2.1 A resolution: evidence for an induced fit model of substrate binding.
- M. Wester, Eric F. Johnson, C. Stout
- Chemistry, BiologyBiochemistry
- 19 July 2003
The structure exhibits conformational changes indicative of an adaptive fit to the substrate reflecting both the hydration and size of the substrate, indicating how structurally diverse substrates are recognized by drug-metabolizing P450 enzymes.
Substrate selectivity of human cytochrome P450 2C9: importance of residues 476, 365, and 114 in recognition of diclofenac and sulfaphenazole and in mechanism-based inactivation by tienilic acid.
- Armelle Melet, N. Assrir, D. Mansuy
- Biology, ChemistryArchives of Biochemistry and Biophysics
- 2003
Selective, competitive and mechanism-based inhibitors of human cytochrome P450 2J2.
- P. Lafite, S. Dijols, D. Zeldin, P. Dansette, D. Mansuy
- Chemistry, BiologyArchives of Biochemistry and Biophysics
- 15 August 2007
Structure of a substrate complex of mammalian cytochrome P450 2C5 at 2.3 A resolution: evidence for multiple substrate binding modes.
- M. Wester, Eric F. Johnson, C. Marques-Soares, P. Dansette, D. Mansuy, C. Stout
- Chemistry, BiologyBiochemistry
- 8 May 2003
The present structure provides a complete model for the protein from residues 27-488 and defines two new helices F' and G'.
Cytochrome p450 enzymes mechanism based inhibitors: common sub-structures and reactivity.
- E. Fontana, P. Dansette, S. Poli
- Biology, ChemistryCurrent drug metabolism
- 30 September 2005
The literature is reviewed and all the available data on chemical entities, which are known to be CYP suicide inhibitors, are compiled to help predict liabilities of new chemical entities without carrying out extensive in vitro work, and will hopefully help in designing safer drugs.
Cytochromes P450 catalyze both steps of the major pathway of clopidogrel bioactivation, whereas paraoxonase catalyzes the formation of a minor thiol metabolite isomer.
- P. Dansette, Julien Rosi, G. Bertho, D. Mansuy
- Biology, ChemistryChemical Research in Toxicology
- 20 February 2012
Chemical experiments on 2-oxo-clopidogrel showed that this thiolactone is in equilibrium with its tautomer having a double bond inside the piperidine ring and that nucleophiles such as CH(3)O(-) preferentially react on the thioester function of this tautomers.
Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs.
- A. Mancy, M. Antignac, D. Mansuy
- Chemistry, BiologyBiochemistry
- 9 October 1999
Results show that diclofenac derivatives are interesting tools to compare the active site topologies of human P450 2Cs, and that oxidation ofdicl ofenac and its derivative 2, either with chemical model systems of cytochrome P450 or with recombinant human P 450s, generally occurs at position 5.
Thiophene derivatives as new mechanism-based inhibitors of cytochromes P-450: inactivation of yeast-expressed human liver cytochrome P-450 2C9 by tienilic acid.
- M. López-Garcı́a, P. Dansette, D. Mansuy
- Biology, ChemistryBiochemistry
- 11 January 1994
TA exhibited all of the characteristics of a mechanism-based inactivator for P 450 2C9 and 2C10 enzymes and could be a starting point for the appearance of anti-P450 2C antibodies detected in patients treated with TA and suffering from immunoallergic hepatitis.
...
...