Abstract:
:The treatment and prevention of atrial fibrillation (AF) remains a significant unmet medical need. Existing therapies that maintain or restore sinus rhythm (rhythm control) have deleterious effects on the ventricle. A major goal for finding new AF therapies is the identification of repolarization mechanisms that are present in the atrium and not in the ventricle. The potassium current I(Kur) has been shown to be selectively involved in atrial repolarization in human tissue. Hence this current and specifically Kv1.5, the protein that underlies it, have become prime targets for the invention of new AF agents. This article reviews the development of Kv1.5 blockers. The discovery and clinical progress of the non-selective Kv1.5 blockers vernakalant and AVE-0118 are highlighted. More selective Kv1.5 blockers in pre-clinical stages of discovery are then reviewed, with a focus on compounds that have been investigated for their in vivo effects on atrial repolarization or on efficacy in pre-clinical models of atrial fibrillation.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Bilodeau MT,Trotter BWdoi
10.2174/156802609788340832subject
Has Abstractpub_date
2009-01-01 00:00:00pages
436-51issue
5eissn
1568-0266issn
1873-4294journal_volume
9pub_type
杂志文章,评审abstract::G protein coupled receptors (GPCRs) are membrane proteins coupled with G proteins through which they transmit signals to the cytoplasm. Approximately 30% of pharmaceuticals target these receptors, even though crystal structures were scarce at the time. Furthermore, an additional 15% of GPCRs have yet to be exploited f...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026615666150915121324
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journal_title:Current topics in medicinal chemistry
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802606777303667
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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abstract:BACKGROUND:Nowadays, malaria is still one of the most important and lethal diseases worldwide, causing 445,000 deaths in a year. Due to the actual treatment resistance, there is an emergency to find new drugs. OBJECTIVE:The aim of this work was to find potential inhibitors of phosphoglycerate mutase 1 from P. falcipar...
journal_title:Current topics in medicinal chemistry
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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journal_title:Current topics in medicinal chemistry
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journal_title:Current topics in medicinal chemistry
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更新日期:2001-06-01 00:00:00
abstract::Tanshinones are a class of bioactive compounds present in the Chinese herbal medicine Danshen (Salvia miltiorrhiza Bunge), containing among others, abietane diterpene quinone scaffolds. Chemical synthesis and biological activity studies of natural and unnatural tanshinone derivatives have been reviewed in this article...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026620666200922115109
更新日期:2020-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026619666190808145235
更新日期:2019-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
abstract:INTRODUCTION:Mosquito borne diseases continue to propagate and cause millions of deaths annually. They are caused either by protozoan parasites such as Plasmodium, Toxoplasma or by flaviviruses including Dengue and Zika. Among the proteome of such parasitic organisms, proteases play essential roles in events such as ho...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2014-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2010-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026618666180116122921
更新日期:2017-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 社论
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journal_title:Current topics in medicinal chemistry
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2015-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2003-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
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更新日期:2020-01-01 00:00:00
abstract::The H(3) histamine receptor is expressed in many brain regions, including those involved in sleep/wake regulation and cognitive functions. Inhibition of the H(3) receptor leads to increased release of multiple neurotransmitters in these regions, making this receptor an ideal target for the potential enhancement of aro...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2010-01-01 00:00:00
abstract::Screening and identifying a disease-specific novel drug target is the first step towards a rational drug designing approach. Due to the advent of high throughput data generation techniques, the protein search space has now exceeded 24,500 human protein coding genes, which encodes approximately 1804proteins. This work ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2018-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2011-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2015-01-01 00:00:00
abstract::Structure-activity relationships of a 4-aminoquinoline MCH-1R antagonist lead series were explored by synthesis of analogs with modifications at the 2-, 4- and 6-positions of the original HTS hit. Improvements to the original screening lead were made by addition of lipophilic groups at the 2-position and biphenyl, cyc...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2007-01-01 00:00:00
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journal_title:Current topics in medicinal chemistry
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更新日期:2009-01-01 00:00:00