Inhibition of cytochromes P450: Existing and new promising therapeutic targets

被引:41
作者
Schuster, Inge
Bernhardt, Rita
机构
[1] Univ Saarland, Inst Chem, D-66041 Saarbrucken, Germany
[2] Univ Vienna, Inst Med Chem, Fak Lebenswissensch, A-1090 Vienna, Austria
关键词
P450; drug target; inhibition;
D O I
10.1080/03602530701498455
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Mammalian cytochromes P450 have been shown to play highly important roles in the metabolism of drugs and xenobiotics as well as in the biosynthesis of a variety of endogenous compounds, many of them displaying hormonal function. The role of P450s as therapeutic targets is still inadequately recognized although several P450 inhibitors become efficient drugs that even reached blockbuster status. Here, we try to give a comprehensive overview on cytochromes P450s, which are already well-established targets - particularly focussing on the treatment of infectious diseases, metabolic disorders and cancer - and on those, which have a high potential to become successful targets. In addition, the design of inhibitors of cytochromes P450 will be discussed.
引用
收藏
页码:481 / 499
页数:19
相关论文
共 103 条
[1]   Ligand probes for heme proteins [J].
Anderson, JLR ;
Chapman, SK .
DALTON TRANSACTIONS, 2005, (01) :13-24
[2]   17-BETA-(CYCLOPROPYLAMINO)-ANDROST-5-EN-3-BETA-OL, A SELECTIVE MECHANISM-BASED INHIBITOR OF CYTOCHROME P45017-ALPHA (STEROID 17-ALPHA HYDROXYLASE-C17-20 LYASE) [J].
ANGELASTRO, MR ;
LAUGHLIN, ME ;
SCHATZMAN, GL ;
BEY, P ;
BLOHM, TR .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1989, 162 (03) :1571-1577
[3]   Improving the outcome of patients with castration-resistant prostate cancer through rational drug development [J].
Attard, G. ;
Sarker, D. ;
Reid, A. ;
Molife, R. ;
Parker, C. ;
de Bono, J. S. .
BRITISH JOURNAL OF CANCER, 2006, 95 (07) :767-774
[5]   INHIBITION OF 17-ALPHA-HYDROXYLASE/C17-C20 LYASE BY BIFLURANOL AND ITS ANALOGS [J].
BARRIE, SE ;
ROWLANDS, MG ;
FOSTER, AB ;
JARMAN, M .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1989, 33 (06) :1191-1195
[6]   PHARMACOLOGY OF NOVEL STEROIDAL INHIBITORS OF CYTOCHROME P450(17-ALPHA) (17-ALPHA-HYDROXYLASE C17-20 LYASE) [J].
BARRIE, SE ;
POTTER, GA ;
GODDARD, PM ;
HAYNES, BP ;
DOWSETT, M ;
JARMAN, M .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1994, 50 (5-6) :267-273
[7]   Modelling of three-dimensional structures of cytochromes P45011B1 and 11B2 [J].
Belkina, NV ;
Lisurek, M ;
Ivanov, AS ;
Bernhardt, R .
JOURNAL OF INORGANIC BIOCHEMISTRY, 2001, 87 (04) :197-207
[8]   Diclofenac-induced liver injury: a paradigm of idiosyncratic drug toxicity [J].
Boelsterli, UA .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2003, 192 (03) :307-322
[9]  
BONKOVSKY HL, 2007, AASLDFDANIHPHRMA HEP
[10]  
BOSTWICK DG, 1992, CANCER, V70, P291, DOI 10.1002/1097-0142(19920701)70:1+<291::AID-CNCR2820701317>3.0.CO