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本文引用的文献

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Cytochrome P450 Enzymes as Drug Targets in Human Disease.细胞色素 P450 酶作为人类疾病的药物靶点。
Drug Metab Dispos. 2024 May 16;52(6):493-497. doi: 10.1124/dmd.123.001431.
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Aldosterone Synthase Inhibition With Lorundrostat for Uncontrolled Hypertension: The Target-HTN Randomized Clinical Trial.用洛鲁司他抑制醛固酮合酶治疗未控制的高血压:TARGET-HTN 随机临床试验。
JAMA. 2023 Sep 26;330(12):1140-1150. doi: 10.1001/jama.2023.16029.
4
Selectivity of osilodrostat as an inhibitor of human steroidogenic cytochromes P450.奥西罗度他作为人源类固醇生成细胞色素 P450 抑制剂的选择性。
J Steroid Biochem Mol Biol. 2023 Jul;231:106316. doi: 10.1016/j.jsbmb.2023.106316. Epub 2023 Apr 23.
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Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension.巴多司他治疗顽固性高血压的2期试验。
N Engl J Med. 2023 Feb 2;388(5):395-405. doi: 10.1056/NEJMoa2213169. Epub 2022 Nov 7.
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First-in-Class Small Molecule to Inhibit CYP11A1 and Steroid Hormone Biosynthesis.首创小分子抑制剂抑制 CYP11A1 和类固醇激素生物合成。
Mol Cancer Ther. 2022 Dec 2;21(12):1765-1776. doi: 10.1158/1535-7163.MCT-22-0115.
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Roles of cytochrome P450 enzymes in pharmacology and toxicology: Past, present, and future.细胞色素 P450 酶在药理学和毒理学中的作用:过去、现在和未来。
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8
Tight binding of cytochrome b to cytochrome P450 17A1 is a critical feature of stimulation of C21 steroid lyase activity and androgen synthesis.细胞色素 b 与细胞色素 P450 17A1 的紧密结合是刺激 C21 甾体裂解酶活性和雄激素合成的关键特征。
J Biol Chem. 2021 Jan-Jun;296:100571. doi: 10.1016/j.jbc.2021.100571. Epub 2021 Mar 20.
9
Levoketoconazole, the 2S,4R Enantiomer of Ketoconazole, a New Steroidogenesis Inhibitor for Cushing's Syndrome Treatment.左酮康唑,酮康唑的 2S,4R 对映异构体,一种治疗库欣综合征的新型甾体生成抑制剂。
J Clin Endocrinol Metab. 2021 Mar 25;106(4):e1618-e1630. doi: 10.1210/clinem/dgaa989.
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Efficacy and safety of osilodrostat in patients with Cushing's disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase.奥昔孕肽治疗库欣病患者的疗效和安全性(LINC 3):一项多中心 III 期研究,包括双盲、随机撤药阶段。
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作为药物靶点的类固醇生成细胞色素P450酶。

Steroidogenic cytochrome P450 enzymes as drug target.

作者信息

Kim Changmin, Jeong Eunseo, Lee Yoo-Bin, Kim Donghak

机构信息

Department of Biological Sciences, Konkuk University, 120 Neungdongro, Gwangjin-gu, Seoul, 05029 Republic of Korea.

出版信息

Toxicol Res. 2024 Apr 22;40(3):325-333. doi: 10.1007/s43188-024-00237-0. eCollection 2024 Jul.

DOI:10.1007/s43188-024-00237-0
PMID:38911541
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11187042/
Abstract

Human cytochrome P450 (CYP) enzymes are composed of 57 individual enzymes that perform monooxygenase activities. They have diverse physiological roles in metabolizing xenobiotics and producing important endogenous compounds, such as steroid hormones and vitamins. At least seven CYP enzymes are involved in steroid biosynthesis. Steroidogenesis primarily occurs in the adrenal glands and gonads, connecting each reaction to substrates and products. Steroids are essential for maintaining life and significantly contribute to sexual differentiation and reproductive functions within the body. Disorders in steroid biosynthesis can frequently cause serious health problems and lead to the development of diseases, such as prostate cancer, breast cancer, and Cushing's syndrome. In this review, we provide current updated knowledge on the major CYP enzymes involved in the biosynthetic process of steroids, with respect to their enzymatic mechanisms and clinical implications for the development of new drug candidates.

摘要

人类细胞色素P450(CYP)酶由57种具有单加氧酶活性的个体酶组成。它们在代谢外源性物质和产生重要内源性化合物(如类固醇激素和维生素)方面具有多种生理作用。至少七种CYP酶参与类固醇生物合成。类固醇生成主要发生在肾上腺和性腺中,将每个反应与底物和产物联系起来。类固醇对于维持生命至关重要,并对体内的性别分化和生殖功能有显著贡献。类固醇生物合成紊乱经常会导致严重的健康问题,并引发疾病的发展,如前列腺癌、乳腺癌和库欣综合征。在本综述中,我们提供了有关参与类固醇生物合成过程的主要CYP酶的最新知识,涉及它们的酶促机制以及对新候选药物开发的临床意义。