Cytochrome P450 Enzymes as Drug Targets in Human Disease

被引：16

作者：

Guengerich, F. Peter ^{[1
,2
]}

机构：

[1] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Sch Med, 638B Robinson Res Bldg, 2200 Pierce Ave, Nashville, TN 37232 USA

来源：

DRUG METABOLISM AND DISPOSITION | 2024年 / 52卷 / 06期

基金：

美国国家卫生研究院;

关键词：

LANOSTEROL 14-ALPHA-DEMETHYLASE CYP51; SYNTHASE CYP11B2 INHIBITORS; CUSHINGS-SYNDROME; DISCOVERY; ANTIFUNGAL; METABOLISM; MECHANISM; SCH-56592; KNOCKOUT; MOLECULE;

D O I：

10.1124/dmd.123.001431

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Although the mention of cytochrome P450 (P450) inhibition usually brings to mind unwanted variability in pharmacokinetics, in several cases P450s are good targets for inhibition. These P450s are essential, but in certain disease states, it is desirable to reduce the concentrations of their products. Most of the attention to date has been with human P450s 5A1, 11A1, 11B1, 11B2, 17A1, 19A1, and 51A1. In some of those cases, there are multiple drugs in use, e.g., exemestane, letrozole, and anastrozole with P450 19A1, the steroid aromatase target in breast cancer. There are also several targets that are less developed, e.g., P450s 2A6, 8B1, 4A11, 24A1, 26A1, and 26B1.

引用

收藏

页码：493 / 497

页数：5

相关论文

共 55 条

[1] Hydroxylated analogues of the orally active broad spectrum antifungal, Sch 51048 (1), and the discovery of posaconazole [Sch 56592; 2 or (S,S)-5] [J].

Bennett, F ;

Saksena, AK ;

Lovey, RG ;

Liu, YT ;

Patel, NM ;

Pinto, P ;

Pike, R ;

Jao, E ;

Girijavallabhan, VM ;

Ganguly, AK ;

Loebenberg, D ;

Wang, HY ;

Cacciapuoti, A ;

Moss, E ;

Menzel, F ;

Hare, RS ;

Nomeir, A .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (01) :186-190

[2] US FDA Approved Drugs from 2015-June 2020: A Perspective [J].

Bhutani, Priyadeep ;

Joshi, Gaurav ;

Raja, Nivethitha ;

Bachhav, Namrata ;

Rajanna, Prabhakar K. ;

Bhutani, Hemant ;

Paul, Atish T. ;

Kumar, Raj .

JOURNAL OF MEDICINAL CHEMISTRY, 2021, 64 (05) :2339-2381

[3] The hunt for a selective 17,20 lyase inhibitor; learning lessons from nature [J].

Bird, Ian M. ;

Abbott, David H. .

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2016, 163 :136-146

[4] The diagnosis of Cushing's syndrome -: Atypical presentations and laboratory shortcomings [J].

Boscaro, M ;

Barzon, L ;

Sonino, N .

ARCHIVES OF INTERNAL MEDICINE, 2000, 160 (20) :3045-3053

[5] Structure of human cortisol-producing cytochrome P450 11B1 bound to the breast cancer drug fadrozole provides insights for drug design [J].

Brixius-Anderko, Simone ;

Scott, Emily E. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2019, 294 (02) :453-460

[6] AROMATASE INHIBITORS AND HORMONE-DEPENDENT CANCERS [J].

BRODIE, AMH ;

BANKS, PK ;

INKSTER, SE ;

DOWSETT, M ;

COOMBES, RC .

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1990, 37 (03) :327-333

[7] Cobicistat: A case of mislabelled drug-drug interaction risk? [J].

Burger, David M. ;

Calmy, Alexandra ;

Marzolini, Catia .

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2020, 86 (05) :834-836

[8] Pharmacokinetics and Pharmacodynamics of Posaconazole [J].

Chen, Lu ;

Krekels, Elke H. J. ;

Verweij, Paul E. ;

Bui, Jochem B. ;

Knibbe, Catherijne A. J. ;

Bruggemann, Roger J. M. .

DRUGS, 2020, 80 (07) :671-695

[9] Slow-, Tight-Binding Inhibition of CYP17A1 by Abiraterone Redefines Its Kinetic Selectivity and Dosing Regimen [J].

Cheong, Eleanor Jing Yi ;

Nair, Pramod C. ;

Neo, Rebecca Wan Yi ;

Ho Thanh Tu ;

Lin, Fu ;

Chiong, Edmund ;

Esuvaranathan, Kesavan ;

Fan, Hao ;

Szmulewitz, Russell Z. ;

Peer, Cody J. ;

Figg, William D. ;

Chai, Christina Li Lin ;

Miners, John O. ;

Chan, Eric Chun Yong .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2020, 374 (03) :438-451

[10] Successful long-term treatment of refractory Cushing's disease with high-dose mifepristone (RU 486) [J].

Chu, JW ;

Matthias, DF ;

Belanoff, J ;

Schatzberg, A ;

Hoffman, AR ;

Feldman, D .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2001, 86 (08) :3568-3573

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