Lewis D F V, Jacobs M N, Dickins M, Lake B G
School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
Toxicology. 2002 Jul 1;176(1-2):51-7. doi: 10.1016/s0300-483x(02)00135-x.
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 alpha (hER alpha), human glucocorticoid receptor (hGR) and the rat peroxisome proliferator-activated receptor alpha (rPPAR alpha).
本文报道了几类细胞色素P450诱导剂的定量构效关系（QSAR）结果，这些诱导剂包括那些还作为参与相关P450基因调控的各种核受体配体的化合物，即CYP1、CYP2、CYP3和CYP4。在给出的几个例子中，QSAR与基于雌激素和过氧化物酶体增殖物激活受体配体结合域（LBD）的现有晶体结构对核受体配体结合域（LBD）进行的同源建模研究一致。对于芳烃受体（AhR）、人雌激素受体α（hERα）、人糖皮质激素受体（hGR）和大鼠过氧化物酶体增殖物激活受体α（rPPARα），在各种结构参数与生物活性（以P450诱导或配体结合亲和力的形式）之间发现了良好的相关性（R = 0.91 - 0.99）。
