Abstract:
:Guanine-rich sequences found in telomeres and oncogene promoters have the ability to form G-quadruplex structures. In this paper we describe the use of a virtual screening assay to search a database of FDA-approved compounds for compounds with the potential to bind G-quadruplex DNA. More than 750 telomerase inhibitors were identified in a literature search as acting through G-quadruplex stabilization, and from evaluation of these compounds, theoretical models capable of discriminating new compounds that bind G-quadruplex DNA were developed. Six compounds predicted to bind to the G-quadruplex structure were tested for their ability to bind to the human telomeric DNA sequence. Prochloroperazine, promazine, and chlorpromazine stabilized the G-quadruplex structure as determined by fluorescence resonance energy transfer techniques. These compounds also bound to promoter sequences of oncogenes such as c-myc and K-ras. Amitriptyline, imipramine, and loxapine were less stabilizing but did bind to the G-quadruplex. The ability of prochloroperazine, promazine, and chlorpromazine to recognize G-quadruplex structures was confirmed using a fluorescent intercalator displacement assay, in which displacement of thiazole orange from G-quadruplex structures was demonstrated. Interestingly, these compounds exhibited selectivity for the G-quadruplex structure as all had poor affinity for the duplex sequence.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Castillo-González D,Pérez-Machado G,Guédin A,Mergny JL,Cabrera-Pérez MAdoi
10.2174/1381612811319120004subject
Has Abstractpub_date
2013-01-01 00:00:00pages
2164-73issue
12eissn
1381-6128issn
1873-4286pii
CPD-EPUB-20120924-18journal_volume
19pub_type
杂志文章abstract::Aspirin is the cornerstone of treatment in patients with coronary artery disease. However, several studies investigating the in vitro response of platelets to the administration of aspirin showed this response to be variable, with some patients exhibiting non-responsiveness or resistance. Aspirin resistance may be cat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787846964
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abstract::Diterpenes present complex structure and due to their unique carbon skeleton and interesting biological activities, have been the focus of continuous studies for the development of new anticancer agents. Phorbol esters have been known for their activity against skin malignancies since ancient times. Taxol was first st...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787354258
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207781662966
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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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journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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更新日期:2013-01-01 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
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更新日期:2004-01-01 00:00:00
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journal_title:Current pharmaceutical design
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更新日期:2010-01-01 00:00:00
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更新日期:2006-01-01 00:00:00
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journal_title:Current pharmaceutical design
pub_type: 杂志文章,meta分析,评审
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更新日期:2017-01-01 00:00:00
abstract::Neuromuscular blocking agents are the leading drugs responsible for immediate hypersensitivity reactions during anaesthesia. Most hypersensitivity reactions represent IgE-mediated allergic reactions. Their incidence is estimated to be between 1 in 3,000 to 1 in 110,000 general anaesthetics. However striking variations...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
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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
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journal_title:Current pharmaceutical design
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更新日期:1999-01-01 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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更新日期:2011-01-01 00:00:00
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journal_title:Current pharmaceutical design
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journal_title:Current pharmaceutical design
pub_type: 历史文章,杂志文章,评审
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更新日期:2018-01-01 00:00:00
abstract::All common contributing factors to epilepsy such as trauma, malignancies and infections are accompanied by different levels of central nervous system inflammation that in turn have been associated with the occurrence of seizure. Emerging data from human brain tissue and experimental models of epilepsy support the prop...
journal_title:Current pharmaceutical design
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更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Protective effect of pretreatment with ghrelin against different forms of acute pancreatitis (AP) has been recently reported. Moreover, the healing properties of this peptide have been proved in AP evoked by cerulein. However, no studies have investigated whether the administration of ghrelin affects the cou...
journal_title:Current pharmaceutical design
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更新日期:2015-01-01 00:00:00
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journal_title:Current pharmaceutical design
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更新日期:2016-01-01 00:00:00
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journal_title:Current pharmaceutical design
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更新日期:2012-01-01 00:00:00