Abstract:
:Androgen receptor (AR) is a steroid hormone receptor that is activated by endogenous androgens, mainly testosterone and 5alpha-dihydrotestosterone (5alpha-DHT). AR is also an important drug target, and AR antagonists (antiandrogens) have been widely used for prostate cancer therapy. Antiandrogens currently available on the market are all small molecules that antagonize AR function via binding to the ligand binding domain (LBD). AR peptide antagonist has been proposed as a 'mechanism-based' approach to directly block AR function by interrupting AR-protein interactions from the surface of the receptor. Without targeting the rigid ligand binding pocket within LBD, peptide antagonists allow more flexibility in structure design, and are likely to provide more efficient and complete blockade of AR function as compared to small molecule antagonists. AR interacts with a variety of proteins, and the interaction may be mediated by different functional domains of the receptor. Although varieties of AR-protein interfaces might serve as the target for peptide antagonist, majority of ongoing research is still focusing on peptides that target the LBD, which is mainly due to the abundance of structural information revealed by crystal structures. This review gives an overview of the current research attempts to develop AR peptide antagonists, particularly peptide antagonists that target the LBD and N-terminal domain (NTD). The challenges and opportunities for future discovery and development of peptide antagonists are discussed as well.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Gao Wdoi
10.2174/138161210790963850subject
Has Abstractpub_date
2010-01-01 00:00:00pages
1106-13issue
9eissn
1381-6128issn
1873-4286pii
BSP/CPD/E-Pub/00012journal_volume
16pub_type
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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更新日期:2008-01-01 00:00:00
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990556
更新日期:2014-01-01 00:00:00
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
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