N P Vermeulen

Summary

Affiliation: Vrije Universiteit
Country: The Netherlands

Publications

  1. ncbi request reprint Enzyme-catalyzed activation of anticancer prodrugs
    Martijn Rooseboom
    Leiden Amsterdam Center for Drug Research L A C D R, Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, Amsterdam, The Netherlands
    Pharmacol Rev 56:53-102. 2004
  2. ncbi request reprint Prediction of drug metabolism: the case of cytochrome P450 2D6
    Nico P E Vermeulen
    LACDR Section Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Curr Top Med Chem 3:1227-39. 2003
  3. ncbi request reprint Toxicity of fotemustine in rat hepatocytes and mechanism-based protection against it
    N P Vermeulen
    Leiden Amsterdam Center for Drug Research, Department of Pharmacochemistry, Vrije Universiteit, Amsterdam, The Netherlands
    Chem Biol Interact 110:139-58. 1998
  4. ncbi request reprint Cytotoxicity of a series of mono- and di-substituted thiourea in freshly isolated rat hepatocytes: a preliminary structure-toxicity relationship study
    R C Onderwater
    Leiden Amsterdam Center for Drug Research, Division of Molecular Toxicology, Vrije Universiteit, Amsterdam, The Netherlands
    Toxicology 125:117-29. 1998
  5. ncbi request reprint Cytochrome P450 catalyzed metabolism of 1,2-dibromoethane in liver microsomes of differentially induced rats
    L W Wormhoudt
    Leiden Amsterdam Center for Drug Research LACDR, Vrije Universiteit, Department of Pharmacochemistry, The Netherlands
    Chem Biol Interact 99:41-53. 1996
  6. ncbi request reprint Urinary thiodiacetic acid. A selective biomarker for the cytochrome P450-catalyzed oxidation of 1,2-dibromoethane in the rat
    L W Wormhoudt
    Leiden Amsterdam Center for Drug Research, Department of Pharmacochemistry, Vrije Universiteit, The Netherlands
    Drug Metab Dispos 25:508-15. 1997
  7. ncbi request reprint Selective induction of cytochrome P450 3A1 by dexamethasone in cultured rat hepatocytes: analysis with a novel reverse transcriptase-polymerase chain reaction assay section sign
    P A Hoen
    Division of Biopharmaceutics, Leiden Amsterdam Center for Drug Research, 2300 RA, Leiden, The Netherlands
    Biochem Pharmacol 60:1509-18. 2000
  8. ncbi request reprint Bioactivation of selenocysteine Se-conjugates by a highly purified rat renal cysteine conjugate beta-lyase/glutamine transaminase K
    J N Commandeur
    Leiden Amsterdam Center for Drug Research, Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit Amsterdam, The Netherlands
    J Pharmacol Exp Ther 294:753-61. 2000
  9. ncbi request reprint Mechanism of protection of ebselen against paracetamol-induced toxicity in rat hepatocytes
    Q J Li
    Department of Pharmacochemistry, Vrije Universiteit Amsterdam, The Netherlands
    Biochem Pharmacol 48:1631-40. 1994
  10. ncbi request reprint Occurrence of a cytochrome P-450-containing mixed-function oxidase system in the pond snail, Lymnaea stagnalis
    M Wilbrink
    Department of Pharmacochemistry, Free University, Amsterdam, The Netherlands
    Xenobiotica 21:223-33. 1991

Collaborators

  • J N Commandeur
  • P J van Bladeren
  • P A Hoen
  • A M Hissink
  • Toyoko Hiroi
  • Pavel Pospisil
  • A Messeguer
  • Chris de Graaf
  • Peter H J Keizers
  • Alois Bonifacio
  • Jeroen Kool
  • Barbara M A van Vugt-Lussenburg
  • Chris Oostenbrink
  • Martijn Rooseboom
  • Cees Gooijer
  • Gert van der Zwan
  • Eva Stjernschantz
  • Barbara M A Lussenburg
  • L W Wormhoudt
  • Jelle Reinen
  • Sebastiaan M van Liempd
  • Hubertus Irth
  • K Anton Feenstra
  • Aldo Jongejan
  • Jennifer Venhorst
  • Micaela C Damsten
  • Robert A B van Waterschoot
  • John H N Meerman
  • Antonius M ter Laak
  • Regina Appiah-Opong
  • R C Onderwater
  • Anna Martínez-Cabot
  • Joran Beckman
  • Richard A Tschirret-Guth
  • Aike Stortelder
  • Rawi Ramautar
  • Tim Schenk
  • Frans J J de Kanter
  • Mats Hidestrand
  • Marola M H van Lipzig
  • M Rooseboom
  • H Orhan
  • J H Ploemen
  • Roald Boegschoten
  • Tineke Zeldenthuis
  • Diego Millo
  • Jon S B de Vlieger
  • L L de Zwart
  • Stephanie B A de Beer
  • Andreas W Ehlers
  • Anna Morató
  • André R Groenhof
  • W M Menge
  • Danny van Elswijk
  • Huub van Rossum
  • Stefan Harmsen
  • Danny A van Elswijk
  • Jeroen Lastdrager
  • Barbara van Vugt-Lussenburg
  • Koop Lammertsma
  • Rolien Bosch
  • Dianne M Maasdijk
  • Petra De Kruijf
  • Eveline Vriese
  • Hansruedi Glatt
  • Tushar van der Wijst
  • Karin Hofstetter
  • Bruno Robert
  • Andreas Schmid
  • Wouter Pos
  • Lloyd C Babel
  • Rob Leurs
  • Gerd Folkers
  • Magnus Ingelman-Sundberg
  • Loek H M Schraven
  • Iwan J P De Esch
  • Ben R van Dijk
  • M Ingelman-Sundberg
  • Mirjam Wamelink
  • Daan Geerke
  • Letty M Mentink
  • Ineke van de Wetering
  • Moira Meijer
  • Yoshihiko Funae
  • Johanna Fink-Gremmels
  • Fatma Durgut
  • Gerben Schaaf
  • B M de Rooij
  • N van Hemert
  • G Sahin

Detail Information

Publications57

  1. ncbi request reprint Enzyme-catalyzed activation of anticancer prodrugs
    Martijn Rooseboom
    Leiden Amsterdam Center for Drug Research L A C D R, Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, Amsterdam, The Netherlands
    Pharmacol Rev 56:53-102. 2004
    ....
  2. ncbi request reprint Prediction of drug metabolism: the case of cytochrome P450 2D6
    Nico P E Vermeulen
    LACDR Section Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Curr Top Med Chem 3:1227-39. 2003
    ....
  3. ncbi request reprint Toxicity of fotemustine in rat hepatocytes and mechanism-based protection against it
    N P Vermeulen
    Leiden Amsterdam Center for Drug Research, Department of Pharmacochemistry, Vrije Universiteit, Amsterdam, The Netherlands
    Chem Biol Interact 110:139-58. 1998
    ..It might, therefore, be worthwhile to investigate the cytoprotective potency of these agents against undesired toxicities of fotemustine in vivo as well...
  4. ncbi request reprint Cytotoxicity of a series of mono- and di-substituted thiourea in freshly isolated rat hepatocytes: a preliminary structure-toxicity relationship study
    R C Onderwater
    Leiden Amsterdam Center for Drug Research, Division of Molecular Toxicology, Vrije Universiteit, Amsterdam, The Netherlands
    Toxicology 125:117-29. 1998
    ....
  5. ncbi request reprint Cytochrome P450 catalyzed metabolism of 1,2-dibromoethane in liver microsomes of differentially induced rats
    L W Wormhoudt
    Leiden Amsterdam Center for Drug Research LACDR, Vrije Universiteit, Department of Pharmacochemistry, The Netherlands
    Chem Biol Interact 99:41-53. 1996
    ....
  6. ncbi request reprint Urinary thiodiacetic acid. A selective biomarker for the cytochrome P450-catalyzed oxidation of 1,2-dibromoethane in the rat
    L W Wormhoudt
    Leiden Amsterdam Center for Drug Research, Department of Pharmacochemistry, Vrije Universiteit, The Netherlands
    Drug Metab Dispos 25:508-15. 1997
    ..In addition to 2-HEMA and S-[2-(N7-guanyl)ethyl]-N-acetyl-l-cysteine, TDA may be a valuable tool for biomonitoring and mechanistic studies into the metabolism and toxicity of 1,2-DBE...
  7. ncbi request reprint Selective induction of cytochrome P450 3A1 by dexamethasone in cultured rat hepatocytes: analysis with a novel reverse transcriptase-polymerase chain reaction assay section sign
    P A Hoen
    Division of Biopharmaceutics, Leiden Amsterdam Center for Drug Research, 2300 RA, Leiden, The Netherlands
    Biochem Pharmacol 60:1509-18. 2000
    ..We conclude that the selective induction of CYP3A1 in dexamethasone-treated rat hepatocytes allows the study of biotransformation reactions by CYP3A1, without interference by any of the other CYP3A isoenzymes...
  8. ncbi request reprint Bioactivation of selenocysteine Se-conjugates by a highly purified rat renal cysteine conjugate beta-lyase/glutamine transaminase K
    J N Commandeur
    Leiden Amsterdam Center for Drug Research, Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit Amsterdam, The Netherlands
    J Pharmacol Exp Ther 294:753-61. 2000
    ..The identity and characteristics of these alternative selenocysteine conjugate beta-lyases, however, remain to be established...
  9. ncbi request reprint Mechanism of protection of ebselen against paracetamol-induced toxicity in rat hepatocytes
    Q J Li
    Department of Pharmacochemistry, Vrije Universiteit Amsterdam, The Netherlands
    Biochem Pharmacol 48:1631-40. 1994
    ..Reduction of NAPQI, the reactive metabolite of paracetamol, by ebselen selenol is discussed in terms of the mechanism of cytoprotection...
  10. ncbi request reprint Occurrence of a cytochrome P-450-containing mixed-function oxidase system in the pond snail, Lymnaea stagnalis
    M Wilbrink
    Department of Pharmacochemistry, Free University, Amsterdam, The Netherlands
    Xenobiotica 21:223-33. 1991
    ..2 nmol biphenyl; in vitro 118 +/- 21 pmol and 21 +/- 9 nmol, respectively (digestive gland homogenate/mg protein, per hour). 7. The results indicate that the isoenzymes involved in the observed MFO activities resemble isoenzymes P-450b/e...
  11. ncbi request reprint Activation of microsomal glutathione S-transferase and inhibition of cytochrome P450 1A1 activity as a model system for detecting protein alkylation by thiourea-containing compounds in rat liver microsomes
    R C Onderwater
    Division of Molecular Toxicology, Leiden Amsterdam Center for Drug Research LACDR, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Chem Res Toxicol 12:396-402. 1999
    ....
  12. ncbi request reprint Disposition of 1,2-[14C]Dibromoethane in male Wistar rats
    L W Wormhoudt
    Leiden Amsterdam Center for Drug Research, Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit, Amsterdam, The Netherlands
    Drug Metab Dispos 26:437-47. 1998
    ....
  13. ncbi request reprint The mechanism of interaction between cisplatin and selenite
    G S Baldew
    Department of Pharmacochemistry, Free University, Amsterdam, The Netherlands
    Biochem Pharmacol 41:1429-37. 1991
    ..It is proposed that the formation of a cisplatin-selenol complex also takes place in vivo, especially in the kidney, thereby preventing cisplatin exerting its nephrotoxic activity...
  14. ncbi request reprint Biomarkers of free radical damage applications in experimental animals and in humans
    L L de Zwart
    Leiden Amsterdam Center for Drug Research, Department of Pharmacochemistry, Vrije Universiteit, The Netherlands
    Free Radic Biol Med 26:202-26. 1999
    ....
  15. ncbi request reprint Characterization of thioether compounds formed from alkaline degradation products of enflurane
    H Orhan
    Division of Molecular Toxicology, Vrije Universiteit, Amsterdam, The Netherlands
    Anesthesiology 95:165-75. 2001
    ..The N-acetyl-L-cysteine S-conjugates identified may be biomarkers to assess exposure of humans to alkaline degradation products of enflurane...
  16. ncbi request reprint Identification and quantitative determination of 3-chloro-2-hydroxypropylmercapturic acid and alpha-chlorohydrin in urine of rats treated with epichlorohydrin
    B M de Rooij
    Leiden Amsterdam Center for Drug Research LACDR, Department of Pharmacochemistry, Free University, Amsterdam, Netherlands
    J Chromatogr B Biomed Appl 685:241-50. 1996
    ..It is anticipated that the analysis of CHPMA and alpha-CH based on GC-MS may be sufficiently sensitive to investigate urinary excretion from humans occupationally exposed to ECH...
  17. ncbi request reprint Genetic polymorphisms of human N-acetyltransferase, cytochrome P450, glutathione-S-transferase, and epoxide hydrolase enzymes: relevance to xenobiotic metabolism and toxicity
    L W Wormhoudt
    Leiden Amsterdam Center for Drug Research, Vrije Universiteit, Department of Pharmacochemistry, The Netherlands
    Crit Rev Toxicol 29:59-124. 1999
    ..This may lead to interindividual variability in efficacy of drugs and disease susceptibility...
  18. ncbi request reprint Midazolam is a phenobarbital-like cytochrome p450 inducer in rats
    P A Hoen
    Leiden Amsterdam Center for Drug Research, Division of Biopharmaceutics, Leiden, The Netherlands
    J Pharmacol Exp Ther 299:921-7. 2001
    ..We conclude that midazolam is a phenobarbital-like CYP inducer in rats. Induction of CYP3A1 by midazolam may have implications for the longitudinal use of midazolam as a probe for analysis of CYP3A expression levels in rats...
  19. ncbi request reprint Bioactivation of chemopreventive selenocysteine Se-conjugates and related amino acids by amino acid oxidases novel route of metabolism of selenoamino acids
    M Rooseboom
    Leiden/Amsterdam Center for Drug Research (LACDR, Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Chem Res Toxicol 14:996-1005. 2001
    ..The potential significance of this novel bioactivation route for the chemopreventive activity of selenocysteine Se-conjugates is discussed...
  20. ncbi request reprint Inter-individual variability in the oxidation of 1,2-dibromoethane: use of heterologously expressed human cytochrome P450 and human liver microsomes
    L W Wormhoudt
    Leiden Amsterdam Center for Drug Research LACDR, Vrije Universiteit, Department of Pharmacochemistry, Netherlands
    Chem Biol Interact 101:175-92. 1996
    ....
  21. pmc Enantioselective substrate binding in a monooxygenase protein model by molecular dynamics and docking
    K Anton Feenstra
    Department of Pharmacochemistry, Division of Molecular Toxicology, Leiden Amsterdam Center for Drug Research, LACDR, Vrije Universiteit, Amsterdam
    Biophys J 91:3206-16. 2006
    ..Novel insights in the binding of ligands to SMO/StyA, provided by the current protein model, will aid the rational design of mutants with specific, altered enantioselective properties...
  22. ncbi request reprint Role of the conserved threonine 309 in mechanism of oxidation by cytochrome P450 2D6
    Peter H J Keizers
    Leiden Amsterdam Center for Drug Research LACDR, Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Biochem Biophys Res Commun 338:1065-74. 2005
    ..These results indicate that T309 in CYP2D6 is involved in maintaining the balance of multiple oxygenating species and thus influences substrate and regioselectivity...
  23. pmc Active-site structure, binding and redox activity of the heme-thiolate enzyme CYP2D6 immobilized on coated Ag electrodes: a surface-enhanced resonance Raman scattering study
    Alois Bonifacio
    Analytical Chemistry and Applied Spectroscopy, Vrije Universiteit Amsterdam, De Boelelaan 1083a, 1081 HV Amsterdam, The Netherlands
    J Biol Inorg Chem 13:85-96. 2008
    ..This behavior indicated that although the enzyme's ability to exchange electrons is not altered by immobilization per se, MUA-coated electrodes are not suited to perform direct electrochemistry of CYP2D6...
  24. ncbi request reprint Identification of critical residues in novel drug metabolizing mutants of cytochrome P450 BM3 using random mutagenesis
    Barbara M A van Vugt-Lussenburg
    LACDR Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 50:455-61. 2007
    ..Computer modeling studies were used to rationalize the effects of the mutations. This study shows that random mutagenesis can be used to identify novel critical residues, and to increase our insight into P450s...
  25. ncbi request reprint Molecular modeling-guided site-directed mutagenesis of cytochrome P450 2D6
    Chris de Graaf
    Leiden Amsterdam Center for Drug Research, Division of Molecular Toxicology, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Curr Drug Metab 8:59-77. 2007
    ..This information is essential for successful pre-experimental virtual screening, as well as accurate hypothesis generation for in vitro studies in drug discovery and development...
  26. ncbi request reprint Development of three parallel cytochrome P450 enzyme affinity detection systems coupled on-line to gradient high-performance liquid chromatography
    Jeroen Kool
    Vrije Universiteit, Department of Pharmacochemistry, LACDR Division of Molecular Toxicology, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Drug Metab Dispos 35:640-8. 2007
    ..The triple parallelized P450-EAD system was shown to enable rapid profiling of individual components in complex mixtures for inhibitory activity to three different P450s...
  27. ncbi request reprint Development and validation of a fluorescence HPLC-based screening assay for inhibition of human estrogen sulfotransferase
    Jelle Reinen
    LACDR Department of Pharmacochemistry, Division of Molecular Toxicology, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands
    Anal Biochem 357:85-92. 2006
    ..The method was demonstrated to be easy, feasible, and highly reproducible for SULT1E1 screening assay inhibition studies...
  28. ncbi request reprint Heterotropic and homotropic cooperativity by a drug-metabolising mutant of cytochrome P450 BM3
    Barbara M A van Vugt-Lussenburg
    LACDR Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Biochem Biophys Res Commun 346:810-8. 2006
    ..Second, this study shows that BM3 can be engineered to a drug-metabolising enzyme, making it a promising candidate to use as biocatalyst in drug discovery and synthesis...
  29. ncbi request reprint Surface-enhanced resonance Raman scattering of cytochrome P450-2D6 on coated silver hydrosols
    Alois Bonifacio
    Laser Centre Analytical Chemistry and Applied Spectroscopy, and LACDR Molecular Toxicology, Department of Chemistry and Pharmaceutical Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Langmuir 23:1860-6. 2007
    ..Moreover, by tuning the wavelength of the exciting laser away from the main absorption band of the heme, the vibrational bands of the SAM coating are observed and analyzed to see how the presence of the protein affects the SAM structure...
  30. pmc Altered spin state equilibrium in the T309V mutant of cytochrome P450 2D6: a spectroscopic and computational study
    Alois Bonifacio
    Department of Chemistry and Pharmaceutical Sciences, Sections of Analytical Chemistry and Applied Spectroscopy ACAS, Organic and Inorganic Chemistry and Molecular Toxicology, Vrije Universiteit, Amsterdam, The Netherlands
    J Biol Inorg Chem 12:645-54. 2007
    ....
  31. pmc Free energies of binding of R- and S-propranolol to wild-type and F483A mutant cytochrome P450 2D6 from molecular dynamics simulations
    Chris de Graaf
    Division of Molecular Toxicology, Department of Chemistry and Pharmaceutical Sciences, Leiden Amsterdam Center for Drug Research LACDR, Vrije Universiteit, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands
    Eur Biophys J 36:589-99. 2007
    ..Careful inspection of the end-points of the MD simulations involved in this approach, allowed for a molecular interpretation of the observed differences...
  32. ncbi request reprint Inhibition of human recombinant cytochrome P450s by curcumin and curcumin decomposition products
    Regina Appiah-Opong
    Division of Molecular Toxicology, Leiden Amsterdam Center for Drug Research LACDR, Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Toxicology 235:83-91. 2007
    ..The decomposition products of curcumin showed no significant inhibitory activities towards the CYPs investigated, and therefore, are not likely to cause drug-drug interactions at the level of CYPs...
  33. ncbi request reprint In vitro bioactivation of 3-(N-phenylamino)propane-1,2-diol by human and rat liver microsomes and recombinant P450 enzymes. Implications for toxic oil syndrome
    Anna Martínez-Cabot
    Department of Biological Organic Chemistry, IIQAB, Consejo Superior de Investigaciones Cientificas, J Girona 18 26, 08034 Barcelona, Spain
    Chem Res Toxicol 20:1218-24. 2007
    ..In rat liver microsomes, P450 enzymes play a key role in the bioactivation of 1, whereas in human liver microsomes, autoxidation appears to be the major mechanism. The implications of these results for toxic oil syndrome are discussed...
  34. ncbi request reprint Cytochrome P450 bio-affinity detection coupled to gradient HPLC: on-line screening of affinities to cytochrome P4501A2 and 2D6
    Jeroen Kool
    LACDR Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Chromatogr B Analyt Technol Biomed Life Sci 858:49-58. 2007
    ..Finally, the on-line CYP2D6 EAD system was used to screen for the inhibitory activities of stereoisomers of a mixture of five methylenedioxy-alkylamphetamines (XTC analogs) on a chiral analytical column...
  35. ncbi request reprint Structural rationalization of novel drug metabolizing mutants of cytochrome P450 BM3
    Eva Stjernschantz
    Leiden Amsterdam Centre for Drug Research, Division of Molecular Toxicology, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Proteins 71:336-52. 2008
    ..This allows for an orientation of the substrates favorable for formation of the major metabolite by P450 BM3...
  36. ncbi request reprint Application of drug metabolising mutants of cytochrome P450 BM3 (CYP102A1) as biocatalysts for the generation of reactive metabolites
    Micaela C Damsten
    LACDR, Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Chem Biol Interact 171:96-107. 2008
    ....
  37. pmc Reversed-phase liquid chromatography coupled on-line to estrogen receptor bioaffinity detection based on fluorescence polarization
    Jelle Reinen
    Department of Chemistry and Pharmaceutical Sciences, LACDR Division of Molecular Toxicology, Vrije Universiteit, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands
    Anal Bioanal Chem 390:1987-98. 2008
    ..It is concluded that the on-line FP-based bioassay can be used to screen for the affinity of compounds without the disturbing occurrence of autofluorescence...
  38. ncbi request reprint Computational prediction of drug binding and rationalisation of selectivity towards cytochromes P450
    Eva Stjernschantz
    Vrije Universiteit Amsterdam, Leiden Amsterdam Centre for Drug Research, Division of Molecular Toxicology, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Expert Opin Drug Metab Toxicol 4:513-27. 2008
    ..Simultaneously, many computational drug-design methods have been developed, and are being applied to study the interactions between drug candidates and cytochrome P450 enzymes (P450s)...
  39. ncbi request reprint Rapid on-line profiling of estrogen receptor binding metabolites of tamoxifen
    Jeroen Kool
    Leiden Amsterdam Center for Drug Research Division of Molecular Toxicology, Department of Chemistry and Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 49:3287-92. 2006
    ..Most of the 14 metabolites detected exhibited affinity for the ERalpha. The HRS methodology shows great potential for metabolite bio-affinity profiling and application in drug discovery and development...
  40. ncbi request reprint Catalytic site prediction and virtual screening of cytochrome P450 2D6 substrates by consideration of water and rescoring in automated docking
    Chris de Graaf
    Leiden Amsterdam Center for Drug Research, Division of Molecular Toxicology, Division of Pharmaceutical Sciences, Department of Chemistry and Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 49:2417-30. 2006
    ....
  41. ncbi request reprint Beta-lyase-dependent attenuation of cisplatin-mediated toxicity by selenocysteine Se-conjugates in renal tubular cell lines
    Martijn Rooseboom
    Leiden Amsterdam Center for Drug Research, Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Pharmacol Exp Ther 301:884-92. 2002
    ..The precise molecular mechanism by which selenols, generated by beta-lyase, provide protection against cisplatin-induced cytotoxicity, however, remains to be established...
  42. ncbi request reprint Comparative study on the bioactivation mechanisms and cytotoxicity of Te-phenyl-L-tellurocysteine, Se-phenyl-L-selenocysteine, and S-phenyl-L-cysteine
    Martijn Rooseboom
    Leiden Amsterdam Center for Drug Research, Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Chem Res Toxicol 15:1610-8. 2002
    ....
  43. ncbi request reprint Homology modeling of rat and human cytochrome P450 2D (CYP2D) isoforms and computational rationalization of experimental ligand-binding specificities
    Jennifer Venhorst
    Department of Pharmacochemistry, Faculty of Sciences, Division of Molecular Toxicology, Leiden Amsterdam Center for Drug Research, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 46:74-86. 2003
    ..The current study thus provides new insights into differences in the active site topology of the investigated CYP2D isoforms...
  44. ncbi request reprint Modeling and molecular dynamics of glutamine transaminase K/cysteine conjugate beta-lyase
    Jennifer Venhorst
    Department of Pharmacochemistry, Division of Molecular Toxicology, Leiden Amsterdam Center for Drug Research LACDR, Vrije Universiteit, De Boelelaan 1083, 1081 HV, Amsterdam, The Netherlands
    J Mol Graph Model 22:55-70. 2003
    ..Ultimately, insight in the binding of ligands to GTK/beta-lyase may result in the rational design of new ligands and selective inhibitors...
  45. ncbi request reprint Prediction of ligand binding affinity and orientation of xenoestrogens to the estrogen receptor by molecular dynamics simulations and the linear interaction energy method
    Marola M H van Lipzig
    Leiden Amsterdam Center for Drug Research, Division of Molecular Toxicology and Division of Molecular Pharmacology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
    J Med Chem 47:1018-30. 2004
    ..61 +/- 0.4 kcal/mol). In conclusion, our LIE model provides a very good method for prediction of absolute ligand binding affinities, as well as binding orientation of ligands...
  46. ncbi request reprint Influence of phenylalanine 120 on cytochrome P450 2D6 catalytic selectivity and regiospecificity: crucial role in 7-methoxy-4-(aminomethyl)-coumarin metabolism
    Peter H J Keizers
    LACDR Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Biochem Pharmacol 68:2263-71. 2004
    ..These data indicate the importance of Phe(120) in the selectivity and regiospecificity in substrate binding and catalysis by CYP2D6...
  47. ncbi request reprint Binding mode prediction of cytochrome p450 and thymidine kinase protein-ligand complexes by consideration of water and rescoring in automated docking
    Chris de Graaf
    Leiden Amsterdam Center for Drug Research, Division of Molecular Toxicology, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 48:2308-18. 2005
    ....
  48. ncbi request reprint Cytochrome p450 in silico: an integrative modeling approach
    Chris de Graaf
    Leiden Amsterdam Center for Drug Research, Division of Molecular Toxicology, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 48:2725-55. 2005
  49. ncbi request reprint Evaluation of alkoxyresorufins as fluorescent substrates for cytochrome P450 BM3 and site-directed mutants
    Barbara M A Lussenburg
    LACDR Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Anal Biochem 341:148-55. 2005
    ..Of these compounds, 8 showed strong inhibition of the BROD activity, demonstrating for the first time that drug-like molecules also can bind with high affinity to BM3 mutants...
  50. ncbi request reprint Development of a novel cytochrome p450 bioaffinity detection system coupled online to gradient reversed-phase high-performance liquid chromatography
    Jeroen Kool
    LACDR Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit, Amsterdam, The Netherlands
    J Biomol Screen 10:427-36. 2005
    ..It is concluded that this novel screening technology offers new perspectives for rapid and sensitive screening of individual compounds in mixtures exhibiting affinity for liver microsomal Cyt P450s...
  51. ncbi request reprint The role of phenylalanine 483 in cytochrome P450 2D6 is strongly substrate dependent
    Barbara M A Lussenburg
    LACDR Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit, HV Amsterdam, The Netherlands
    Biochem Pharmacol 70:1253-61. 2005
    ..The presented data show that next to F120, residue F483 plays a very important role in the metabolism of typical CYP2D6 substrates. The influence of F483 on metabolism was found to be strongly substrate-dependent...
  52. ncbi request reprint Metabolic regio- and stereoselectivity of cytochrome P450 2D6 towards 3,4-methylenedioxy-N-alkylamphetamines: in silico predictions and experimental validation
    Peter H J Keizers
    Leiden Amsterdam Center for Drug Research LACDR Division of Molecular Toxicology and Division of Organic and Inorganic Chemistry, Department of Chemistry and Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    J Med Chem 48:6117-27. 2005
    ..Differences in regioselectivity and stereoselectivity in the oxidative metabolism of the MDAAs by the Phe120Ala mutant CYP2D6 were correctly predicted, and the effects of the Phe120Ala mutation could be rationalized as well...
  53. pmc Binding of 7-methoxy-4-(aminomethyl)-coumarin to wild-type and W128F mutant cytochrome P450 2D6 studied by time-resolved fluorescence spectroscopy
    Aike Stortelder
    Laser Centre VU, Department of Analytical Chemistry and Applied Spectroscopy, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Biochem J 393:635-43. 2006
    ..However, the changes in the overall enzyme structure were not very large, since the emission characteristics of the enzyme were not very different in the presence of MAMC...
  54. ncbi request reprint The role and application of in silico docking in chemical genomics research
    Aldo Jongejan
    Division of Medicinal Chemistry, Leiden Amsterdam Center for Drug Research, Faculty of Sciences, Vrije Universiteit, Amsterdam, The Netherlands
    Methods Mol Biol 310:63-91. 2005
    ..We also cover the analysis and rescoring of the obtained docking poses. Possible pitfalls in the docking studies are discussed and hints are provided to resolve commonly occurring problems...
  55. ncbi request reprint Topological role of cytochrome P450 2D6 active site residues
    Robert A B van Waterschoot
    LACDR Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
    Arch Biochem Biophys 447:53-8. 2006
    ....
  56. ncbi request reprint Binding of bufuralol, dextromethorphan, and 3,4-methylenedioxymethylamphetamine to wild-type and F120A mutant cytochrome P450 2D6 studied by resonance Raman spectroscopy
    Alois Bonifacio
    Laser Centre Analytical Chemistry and Applied Spectroscopy, Vrije Universiteit Amsterdam, The Netherlands
    Biochem Biophys Res Commun 343:772-9. 2006
    ..These differences could be explained postulating a different substrate mobility for each compound in the CYP2D6 active site, consistently with the role previously suggested for Phe120 in binding dextromethorphan and MDMA...
  57. ncbi request reprint Enzymatic pathways of beta elimination of chemopreventive selenocysteine Se conjugates
    Martijn Rooseboom
    Leiden Amsterdam Center for Drug Research, Division of Molecular Toxicology, Department of Pharmacochemistry, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands
    Methods Enzymol 348:191-200. 2002