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
[11]  
2-4
[12]   Conferring aldosterone synthesis to human CYP11B1 by replacing key amino acid residues with CYP11B2-specific ones [J].
Böttner, B ;
Denner, K ;
Bernhardt, R .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1998, 252 (03) :458-466
[13]  
Bottner B, 1996, J BIOL CHEM, V271, P8028
[14]  
Bottner B, 1996, ENDOCR RES, V22, P455
[15]   Aldosterone and myocardial fibrosis in heart failure [J].
Brilla, CG .
HERZ, 2000, 25 (03) :299-306
[16]   Vitamin D [J].
Brown, AJ ;
Dusso, A ;
Slatopolsky, E .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 1999, 277 (02) :F157-F175
[17]   Aromatase inhibitors in the treatment of breast cancer [J].
Brueggemeier, RW ;
Hackett, JC ;
Diaz-Cruz, ES .
ENDOCRINE REVIEWS, 2005, 26 (03) :331-345
[18]   Development of test systems for the discovery of selective human aldosterone synthase (CYP11B2) and 11b-hydroxylase (CYP11B1) inhibitors.: Discovery of a new lead compound for the therapy of congestive heart failure, myocardial fibrosis and hypertension [J].
Bureik, M ;
Hübel, K ;
Dragan, CA ;
Scher, J ;
Becker, H ;
Lenz, N ;
Bernhardt, R .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2004, 217 (1-2) :249-254
[19]   Adrenal proteins bound by a reactive intermediate of mitotane [J].
Cai, W ;
Counsell, RE ;
Schteingart, DE ;
Sinsheimer, JE ;
Vaz, ADN ;
Wotring, LL .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 1997, 39 (06) :537-540
[20]   Inhibitors of cytochrome p450 4A suppress angiogenic responses [J].
Chen, P ;
Guo, M ;
Wygle, D ;
Edwards, PA ;
Falck, JR ;
Roman, RJ ;
Scicli, AG .
AMERICAN JOURNAL OF PATHOLOGY, 2005, 166 (02) :615-624