Quantitative structure : activity relationships for inducers of cytochromes P450 and nuclear receptor ligands involved in P450 regulation within the CYP1, CYP2, CYP3 and CYP4 families
article
The results of quantitative structure-activity relationships (QSARs) are reported for several series of cytochrome P450 inducers, including those which also act as ligands for the various nuclear receptors involved in regulation of the relevant P450 genes, namely, CYP1, CYP2, CYP3 and CYP4. In several examples presented, the QSARs are consistent with homology modelling studies of the nuclear receptor ligand-binding domains (LBDs) based on available crystal structures of the oestrogen and peroxisome proliferator-activated receptors' LBDs. Good correlations (R=0.91-0.99) are found between various structural parameters and biological activity (either in the form of P450 induction or ligand-binding affinity) for the Ah receptor (AhR), human estrogen receptor α (hERα), human glucocorticoid receptor (hGR) and the rat peroxisome proliferator-activated receptor α (rPPARα). © 2002 Elsevier Science Ireland Ltd. All rights reserved.
Topics
CytochromesHomology modelling studiesNuclear receptor ligandsQuantitative structure-activity relationshipsCell nucleus receptorCytochrome P450Cytochrome P450 1Cytochrome P450 2Cytochrome P450 3Cytochrome P450 4Estrogen receptorLigandPeroxisome proliferator activated receptorUnclassified drugBinding affinityBioavailabilityControlled studyCorrelation functionCrystal structureHumanModelNonhumanPriority journalProtein bindingProtein domainQuantitative structure activity relationRegulatory mechanismSequence homologyAnimalsCytochrome P-450 Enzyme SystemEnzyme InductionGene Expression RegulationHumansLigandsQuantitative Structure-Activity RelationshipRatsReceptors, Cytoplasmic
TNO Identifier
57537
Source
Toxicology, 176, pp. 51-57.
Pages
51-57
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