Targeting the Androgen Receptor with Steroid Conjugates

被引：32

作者：

Levine, Paul M. ^{[1
]}

Garabedian, Michael J. ^{[2
,3
]}

Kirshenbaum, Kent ^{[1
]}

机构：

[1] NYU, Dept Chem, New York, NY 10003 USA

[2] NYU Langone Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA

[3] NYU Langone Sch Med, Dept Urol, New York, NY 10016 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 57卷 / 20期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

PROSTATE-CANCER CELLS; SMALL-MOLECULE INHIBITORS; NUCLEAR RECEPTOR; STRUCTURAL BASIS; BINDING DOMAIN; CONFORMATIONAL-CHANGE; DEPRIVATION THERAPY; TESTOSTERONE LEVELS; ANTITUMOR-ACTIVITY; AMINO-ACID;

D O I：

10.1021/jm500101h

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The androgen receptor (AR) is a major therapeutic target in prostate cancer pharmacology. Progression of prostate cancer has been linked to elevated expression of AR in malignant tissue, suggesting that AR plays a central role in prostate cancer cell biology. Potent therapeutic agents can be precisely crafted to specifically target AR, potentially averting systemic toxicities associated with nonspecific chemotherapies. In this review, we describe various strategies to generate steroid conjugates that can selectively engage AR with high potency. Analogies to recent developments in nonsteroidal conjugates targeting AR are also evaluated. Particular focus is placed on potential applications in AR pharmacology. The review culminates with a description of future prospects for targeting AR.

引用

页码：8224 / 8237

页数：14

共 111 条

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