Structural characteristics of human P450s involved in drug metabolism: QSARs and lipophilicity profiles

被引：61

作者：

Lewis, DFV ^{[1
]}

机构：

[1] Univ Surrey, Sch Biol Sci, Mol Toxicol Grp, Guildford GU2 5XH, Surrey, England

来源：

TOXICOLOGY | 2000年 / 144卷 / 1-3期

关键词：

cytochromes P450; drug metabolism; lipophilicity; QSARs;

D O I：

10.1016/S0300-483X(99)00207-3

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The factors with human P450 substrate selectivity are reviewed, together with extensive tabulation of quantitative relationships between structure and activity for many species of P450 substrates, inducers and inhibitors. In addition, the physicochemical characteristics (log P and pK(a) values) of heptic microsomal P450 substrates are collated, such that comparisons can be made on the grounds of compound lipophilicities. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

引用

页码：197 / 203

页数：7

共 37 条

[11] Molecular modelling of human CYP2C subfamily enzymes CYP2C9 and CYP2C19: rationalization of substrate specificity and site-directed mutagenesis experiments in the CYP2C subfamily [J].

Lewis, DFV ;

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Eddershaw, PJ ;

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XENOBIOTICA, 1998, 28 (03) :235-268

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Lewis, DFV ;

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XENOBIOTICA, 1999, 29 (08) :763-781

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Lewis, DFV ;

Eddershaw, PJ ;

Goldfarb, PS ;

Tarbit, MH .

XENOBIOTICA, 1997, 27 (04) :319-339

[14]

Lewis DFV, 1996, XENOBIOTICA, V26, P1067

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Lewis, DFV .

DRUG METABOLISM REVIEWS, 1997, 29 (03) :589-650

[16] Molecular modelling of CYP2B6, the human CYP2B isoform, by homology with the substrate-bound CYP102 crystal structure:: evaluation of CYP2B6 substrate characteristics, the cytochrome b5 binding site and comparisons with CYP2B1 and CYP2B4 [J].

Lewis, DFV ;

Lake, BG ;

Dickins, M ;

Eddershaw, PJ ;

Tarbit, MH ;

Goldfarb, PS .

XENOBIOTICA, 1999, 29 (04) :361-393

[17] The CYP2 family: models, mutants and interactions [J].

Lewis, DFV .

XENOBIOTICA, 1998, 28 (07) :617-661

[18] Structural determinants of cytochrome P450 substrate specificity, binding affinity and catalytic rate [J].

Lewis, DFV ;

Eddershaw, PJ ;

Dickens, M ;

Tarbit, MH ;

Goldfarb, PS .

CHEMICO-BIOLOGICAL INTERACTIONS, 1998, 115 (03) :175-199

[19] The P450 catalytic cycle and oxygenation mechanism [J].

Lewis, DFV ;

Pratt, JM .

DRUG METABOLISM REVIEWS, 1998, 30 (04) :739-786

[20] Frontier orbitals in chemical and biological activity: Quantitative relationships and mechanistic implications [J].

Lewis, DFV .

DRUG METABOLISM REVIEWS, 1999, 31 (03) :755-816

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