Abstract:
:Voltage-gated sodium channels are large transmembrane protein complexes responsible for the propagation and transmission of electrical impulses through nerve, muscle and endocrine cells and cell systems. Dysregulated expression and/or functional changes of ion channel isoforms are found in many associated pathological conditions. In such cases, modulation of voltage gated sodium channels (Na(V) channels) is a recognised approach in medicinal chemistry. Multiple small-molecule active compounds are used for a plethora of Na(V) channel-linked indications, for example epilepsy and CNS disorders, arrhythmia, stroke and pain states such as congenital analgesia/hyperalgesia and neuropathic pain. As existent Na(V) channel modulators suffer mainly from selectivity issues and thus exert significant side effects, novel and selective Na(V) channel modulators would be beneficial. Consequently, the increased research on voltage-gated sodium channels has led to a large number of novel compounds that exploit classic binding site selectivity with state-dependence or functional selectivity. Such compounds offer selective targeting and new possibilities for studying the physiology of Na(V) channels and pathophysiology of the associated ailment conditions. This review consolidates the recent literature on Na(V) 1.3, 1.7 and 1.8 channel isoform selective and/or state-dependent modulators. In particular, their structure-activity relationship is illustrated, especially in the context of selectivity on a particular isoform, and their applicability in the therapy of neuropathic pain is described.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Jukič M,Kikelj D,Anderluh Mdoi
10.2174/09298673113206660257subject
Has Abstractpub_date
2014-01-01 00:00:00pages
164-86issue
2eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-56033journal_volume
21pub_type
杂志文章,评审abstract::Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It can occur at any age, however, it becomes extremely common in the elderly, with a prevalence approaching more than 20% in patients older than 85 years. AF is associated with a wide range of cardiac and extra-cardiac complications and there...
journal_title:Current medicinal chemistry
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doi:10.2174/092986711796642373
更新日期:2011-01-01 00:00:00
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abstract::This review presents the detailed account of factors leading to cancer and design strategy for the synthesis of benzimidazole derivatives as anticancer agents. The recent survey for cancer treatment in Cancer facts and figures 2017 American Chemical Society has shown progressive development in fighting cancer. Researc...
journal_title:Current medicinal chemistry
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更新日期:2020-01-01 00:00:00
abstract:OBJECTIVES:Post-exercise cardiac troponin T (cTnT) release has been widely reported in adult athletes but limited data is available for adolescents. The aim of this study was to determine the incidence and magnitude of cTnT appearance in a large group of adolescent runners, and to determine any association between cTnT...
journal_title:Current medicinal chemistry
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更新日期:2011-01-01 00:00:00
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journal_title:Current medicinal chemistry
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doi:10.2174/0929867311209025011
更新日期:2012-01-01 00:00:00
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journal_title:Current medicinal chemistry
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更新日期:2012-01-01 00:00:00
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journal_title:Current medicinal chemistry
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更新日期:2011-01-01 00:00:00
abstract::Limitations associated with the production cost, metabolic instability, side-effects, resistance and poor pharmacokinetics of organic protease inhibitors (PIs), which form an essential component of the front line HAART treatment for HIV, have fuelled efforts into finding novel, transition metal-based alternatives. Som...
journal_title:Current medicinal chemistry
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更新日期:2013-01-01 00:00:00
abstract::Osteogenic peptides are, or have potential to be, therapies for the treatment of osteoporosis, fracture repair, and repair of loosened bone implants. Human parathyroid hormone has been approved for the treatment of post-menopausal osteoporosis. Constrained analogs of PTH and the parathyroid-hormone related peptide (PT...
journal_title:Current medicinal chemistry
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更新日期:2004-11-01 00:00:00
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journal_title:Current medicinal chemistry
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更新日期:2006-01-01 00:00:00
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journal_title:Current medicinal chemistry
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更新日期:2019-03-27 00:00:00
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journal_title:Current medicinal chemistry
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更新日期:2005-01-01 00:00:00
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journal_title:Current medicinal chemistry
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更新日期:2013-01-01 00:00:00
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journal_title:Current medicinal chemistry
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更新日期:2016-01-01 00:00:00
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journal_title:Current medicinal chemistry
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更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Nitric oxide (NO) plays important regulatory roles in a plethora of biological functions and thus holds tremendous potential to be exploited for clinical uses. However, the chemistries in the molecular design of nano-nitric oxide delivery systems is currently lacking. OBJECTIVE:The overarching aim of this r...
journal_title:Current medicinal chemistry
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更新日期:2018-01-01 00:00:00
abstract::Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone secreted from endocrine cells in the gut mucosa in response to meal ingestion. It is an important incretin hormone; mice with a null mutation in the GLP-1 receptor gene develop glucose intolerance. In addition, it inhibits gastrointestinal secretion and moti...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1999-11-01 00:00:00
abstract::For many years the spotlight in drug discovery has been on a relatively small number of validated therapeutic target classes, such as G-protein coupled receptors and enzymes such as protein kinases, with well characterized enzymatic and cellular activities. However, with recent progress in genomics and proteomics, pro...
journal_title:Current medicinal chemistry
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更新日期:2013-01-01 00:00:00
abstract::Apoptosis or programmed cell death is a cellular mechanism used to regulate cell number and eliminate damaged or mutated cells. Many chemotherapeutic agents and ionizing radiation induce not only apoptotic signaling pathways, but also survival responses such as DNA damage responses and cell cycle arrest, which allow f...
journal_title:Current medicinal chemistry
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doi:10.2174/092986707780362844
更新日期:2007-01-01 00:00:00
abstract::The deposition of β-amyloid (Aβ) plaques in the parenchymal and cortical brain is accepted as the main pathological hallmark of Alzheimer's disease (AD). According to the amyloid cascade hypothesis, the Aβ deposition in the brain appears to be a good diagnostic biomarker for AD and may also be a good predictive biomar...
journal_title:Current medicinal chemistry
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更新日期:2014-01-01 00:00:00
abstract::Mast cells are potent effectors playing a key role in IgE-associated hypersensitivity reactions, allergic disorders, inflammation and protective immune responses. Mast cell development in vivo occurs mainly in non-hematopoietic microenvironments and increased mast cell numbers can be seen in various inflammatory disea...
journal_title:Current medicinal chemistry
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更新日期:2007-01-01 00:00:00
abstract::The cation-independent mannose 6-phosphate receptor is a multifunctional protein which binds at the cell surface to two distinct classes of ligands, the mannose 6-phosphate (M6P) bearing proteins and IGF-II. Its major function is to bind and transport M6P-enzymes to lysosomes, but it can also modulate the activity of ...
journal_title:Current medicinal chemistry
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更新日期:2007-01-01 00:00:00
abstract::Bipolar disorder (BD) is a long-term illness with mood swings which are characterized by recurrent episodes of mania/hypomania and depression, with variable interpolations of relatively asymptomatic periods, called euthymic, in which, however, some psychopathological symptoms may persist. Although mood stabilizers, su...
journal_title:Current medicinal chemistry
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更新日期:2009-01-01 00:00:00
abstract::The use of antisense oligonucleotides as therapeutic agents has generated considerable enthusiasm in the research and medical community. Antisense oligonucleotides as therapeutic agents were proposed as far back as in the 1970s when the antisense strategy was initially developed. Nonetheless, it has taken almost a qua...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2005-01-01 00:00:00
abstract::Protein C is a vitamin K-dependent anticoagulant serine protease zymogen in plasma which upon activation by the thrombin-thrombomodulin complex down-regulates the coagulation cascade by degrading cofactors Va and VIIIa by limited proteolysis. In addition to its anticoagulant function, activated protein C (APC) also bi...
journal_title:Current medicinal chemistry
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更新日期:2010-01-01 00:00:00
abstract::Gene expression profiles are unveiling a wealth of new potential drug targets for a wide range of diseases, offering new opportunities for drug discoveries. The emerging challenge, however, is the effective selection of the myriad of targets to identify those with the most therapeutic utility. Numerical clustering has...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2005-01-01 00:00:00
abstract::Many of the currently available treatments for obsessive-compulsive and related disorders (OCRDs) such as pharmacotherapy augmentation strategies, partial hospitalization programs, deep brain stimulation, and neurosurgery are efficacious for individuals suffering from more severe forms of these conditions. Unfortunate...
journal_title:Current medicinal chemistry
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更新日期:2018-01-01 00:00:00
abstract::Since the discovery of penicillin, natural and synthetic β-lactams have aroused great interest not only as sources of effective antibacterial agents but also as specific inhibitors of proteases responsible for various non-bacterial pathological processes. This interest was reflected in our review published in Current ...
journal_title:Current medicinal chemistry
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更新日期:2014-01-01 00:00:00
abstract::Trypanosomatids are a group of flagellated unicellular eukaryotes, causing serious human diseases including Chagas disease (Trypanosoma cruzi), sleeping sickness (Trypanosoma brucei spp.) and Leishmaniasis (Leishmania spp.). The second messenger cAMP is involved in numerous and fundamental processes in these parasites...
journal_title:Current medicinal chemistry
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更新日期:2019-01-01 00:00:00
abstract::Sulfonyl group-containing compounds constitute an important class of therapeutical agents in medicinal chemistry presumably because of the tense chemical structure and functionality of the sulfonyl, which could not only form hydrogen bonding interactions with active site residues of biological targets but also, as inc...
journal_title:Current medicinal chemistry
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更新日期:2012-01-01 00:00:00