Abstract:
:Functioning of G protein-coupled receptors (GPCRs) is tightly linked to the membrane environment, but a molecular level understanding of the modulation of GPCR by membrane lipids is not available. However, specific receptor-lipid interactions as well as unspecific effects mediated by the bulk properties of the membrane (thickness, curvature, etc.) have been proposed to be key regulators of GPCR modulation. In this review, we examine computational efforts made towards modeling and simulation of (i) the complex behavior of membrane lipids, (ii) membrane lipid-GPCR interactions as well as membrane lipid-mediated effects on GPCRs and (iii) GPCR oligomerization in a native-like membrane environment. We propose that, from the perspective of computational modeling, all three of these components need to be addressed in order to achieve a deeper understanding of GPCR functioning. Presently, we are able to simulate numerous lipid properties applying advanced computational techniques, although some barriers, such as the time-length of these simulations, need to be overcome. Implementing three-dimensional structures of GPCRs in such validated membrane systems can give novel insights in membrane-dependent receptor modulation and formation of higher order receptor complexes. Finally, more realistic GPCR-membrane models would provide a very useful tool in studying receptor behavior and its modulation by small drug-like ligands, a relevant issue for drug discovery.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Sadiq SK,Guixa-Gonzalez R,Dainese E,Pastor M,De Fabritiis G,Selent Jsubject
Has Abstractpub_date
2013-01-01 00:00:00pages
22-38issue
1eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-20121108-3journal_volume
20pub_type
杂志文章,评审abstract::A large number of children in the autism spectrum disorder suffer from gastrointestinal (GI) conditions, such as constipation and diarrhea. Clostridium bolteae is a part of a set of pathogens being regularly detected in the stool samples of hosts affected by GI and autism symptoms. Accompanying studies have pointed ou...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867326666190225164527
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abstract::Mast cells are best known as central effector cells in IgE-mediated type I allergic diseases including asthma and hay fever. An increasing amount of evidence, however, has demonstrated that mast cells are sentinel cells playing a critical role in host defense against invading microbes. Mast cells are located immediate...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712799828319
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abstract::Whilst knowledge of basic biology, diagnosis and prognosis of glioblastoma (GB - WHO grade IV) are steadily improving, advancements of therapy are discouragingly slow, with the only significant novelty during last ten years represented by introduction of temozolomide in chemotherapy. In order to analyze the current st...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867322666150530210700
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abstract::Drug resistance is one of the major obstacles limiting the success of cancer chemotherapy. Biological mechanisms contributing to drug resistance may be present de novo and related to inherent features or may be raised after exposure to anticancer drugs. In recent years, both clinical observations and experimental stud...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711797379348
更新日期:2011-01-01 00:00:00
abstract::Cell products are live cells that are given to patients in order to replace or modify the function of missing or dysfunctional cells. Progress in technology and in the understanding of pathobiology may lead to the use of cell products in many areas. This review outlines the use of cell products in the treatment of aut...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867023369600
更新日期:2002-08-01 00:00:00
abstract::Inflammation plays a critical role in the atherosclerotic process in various vascular beds, starting from endothelial dysfunction and counting all stages of plaque development. The significant contribution of inflammation in the initiation and progression of atherosclerosis has been documented over many years but its ...
journal_title:Current medicinal chemistry
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abstract::Obesity and metabolic syndrome represent major public health problems, and are the biggest preventable causes of death worldwide. Obesity is the leading risk factor for type 2 diabetes mellitus (T2DM), cardiovascular diseases and non-alcoholic fatty liver disease. Obesity-associated insulin resistance, which is charac...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867311320210001
更新日期:2013-01-01 00:00:00
abstract::During this past decade, science and engineering have seen a rapid increase in interest for nanoscale materials with dimensions less than 100 nm, which lie in the intermediate state between atoms and bulk (solid) materials. Their attributes are significantly altered relative to the corresponding bulk materials as they...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986710791959765
更新日期:2010-01-01 00:00:00
abstract::Kit is a growth factor receptor of the type III tyrosine kinase family, whose gain-of-function mutations have been identified as driving causes of different kinds of tumours. It thus represents a viable drug target, and the development of Kit inhibitors has been shown to be a promising therapeutic concept. This review...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711796150504
更新日期:2011-01-01 00:00:00
abstract::DNA mutation is a very important step in carcinogenesis and elevated levels of oxidative DNA damage have been monitored in a variety of tumors. The discovery of the role of free radicals in cancer has led to a new medical approach. Minimizing oxidative damage may be a significant advance in the prevention or treatment...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/09298673113203690142
更新日期:2013-01-01 00:00:00
abstract::Cannabinoids in current use such as nabilone activate both CB1 and CB2 receptors. Selective CB2 activation may provide some of the therapeutic effects of cannabinoids, such as their immuno-modulatory properties, without the psychoactive effects of CB1 activation. Therefore, cannabinoid CB2 receptors represent an attra...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708784567716
更新日期:2008-01-01 00:00:00
abstract::The synthesis of oxacephalotin and oxacephamandol, which are more active than natural, sulfur-containing congeners, and the isolation of clavulanic acid, a potent inhibitor of beta-lactamase enzymes, directed attention of many academic and industrial laboratories the synthesis of oxygen analogues of penicillins and ce...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2004-07-01 00:00:00
abstract::Inflammation is a local or systemic tissue reaction caused by external or internal stimuli with the objective to remove the noxa, inhibit its further dissemination and eventually repair damaged tissue. Blood vessels and perivascular connective tissue are important regulators of the inflammatory process. After a short ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709789760751
更新日期:2009-01-01 00:00:00
abstract::Anticancer drugs are often nonselective antiproliferative agents (cytotoxins) that preferentially kill dividing cells by attacking their DNA at some level. The lack of selectivity results in significant toxicity to noncancerous proliferating cells. These toxicities along with drug resistance exhibited by the solid tum...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986708785132997
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is the leading cause of cryptogenic cirrhosis and has consistently been implicated in related metabolic disorders, such as dyslipidemia and type 2 diabetes (T2D). However, the pathogenesis of NAFLD remains to be elucidated, and ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170404142450
更新日期:2018-01-01 00:00:00
abstract::O-Prenyl secondary metabolites (3,3-dimethylallyl, geranyl-, farnesyl- and related biosynthetic derivatives) represent a class of rarely occurring natural products. In the last two decades such compounds have been found to exert promising and effective pharmacological activities, mainly in terms of anti-cancer propert...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867322666150716114758
更新日期:2015-01-01 00:00:00
abstract::The present paper summarizes the possible roles of frequent and unfavourable genetic variants in cerebrovascular disorders, such as stroke and leukoaraiosis. It also approaches the topic theoretically from functional and mathematical points of view, which can help make the accumulating data on genetic variants more un...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709788803006
更新日期:2009-01-01 00:00:00
abstract::The serine protease thrombin is a key enzyme in the control of blood coagulation and displays numerous other effects on platelet, endothelial and smooth muscle cell function. The pre-eminence of thrombin in the coagulation cascade has made the enzyme a popular drug target in the search for more clinically acceptable a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1998-12-01 00:00:00
abstract::The term Lewy body diseases (LBDs) refers to a subset of neurodegenerative disorders that share the accumulation of the so-called Lewy bodies (LB) including: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and PD later characterized by the occurrence of dementia (PDD). Moreover, multiple system atrophy (MSA...
journal_title:Current medicinal chemistry
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更新日期:2018-01-01 00:00:00
abstract::The arachidonic acid metabolizing enzymes, cyclooxygenase-2 (COX-2) and 5- lipoxygenase (5-LOX), are both highly expressed during the carcinogenesis in colons. Cigarette smoking promotes these carcinogenic processes at the early stage during adenoma formation. In this article, the involvement of COX-2 and 5-LOX, along...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2016-01-01 00:00:00
abstract::Over the past few years, use of the genome-wide association study (GWAS) has made it possible to identify the primary genetic mechanisms of essential hypertension. GWAS results have helped identify many loci in or near genes that generally were not expected to be associated with blood pressure or essential hypertensio...
journal_title:Current medicinal chemistry
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更新日期:2015-01-01 00:00:00
abstract::Mitochondria are organelles which play an important role not only in cellular metabolism but also in controlling pathways related with cell death, ionic and redox regulation. Alterations in mitochondrial metabolism are implicated in a variety of diseases, including cancer. Cellular and mitochondrial metabolism are bot...
journal_title:Current medicinal chemistry
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更新日期:2015-01-01 00:00:00
abstract::Within the pharmaceutical industry, the ultimate source of continuing profitability is the unremitting process of drug discovery. To be profitable, drugs must be marketable: legally novel, safe and relatively free of side effects, efficacious, and ideally inexpensive to produce. While drug discovery was once typified ...
journal_title:Current medicinal chemistry
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doi:10.2174/092986706776873005
更新日期:2006-01-01 00:00:00
abstract::Platinum complex-based chemotherapy is one of the major treatment options of many malignancies. Although severe side effects occur, and only a limited spectrum of tumors can be cured, Pt compounds are used in every second therapy scheme. Thus, many different drug design strategies have been employed for improving the ...
journal_title:Current medicinal chemistry
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更新日期:2008-01-01 00:00:00
abstract::Vitamin D has been known for a long time as a major factor involved in the calcium- phosphate balance and homeostasis, along with parathyroid hormone (PTH). While vitamin D effects on calcium and phosphate are fully known, recent studies attempted to link vitamin D status and cardiovascular diseases. The involvement o...
journal_title:Current medicinal chemistry
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更新日期:2016-01-01 00:00:00
abstract::Whether the increased atrial fibrillation (AF) risk in metabolic syndrome (MetS) patients is due to the syndrome as a whole or simply the sum of the risks of its individual component parts is still obscure. These two clinical entities share many pathophysiological links and thus distinction between a casual observatio...
journal_title:Current medicinal chemistry
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更新日期:2019-01-01 00:00:00
abstract::Ageing is an aggravating factor leading to alterations in the biotransformation of drugs, and therefore their therapeutic efficacy and safety. In this review we discuss the influence of ageing on drug metabolizing enzymes in male Wistar rats. We report that drug metabolizing enzymes can be affected by ageing either by...
journal_title:Current medicinal chemistry
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更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Numerous studies have reported sex and gender differences in the prevalence and treatment of cardiovascular diseases. However, sex differences in the therapy of hypertension have not been completely examined. OBJECTIVE:To estimate the gender-specific dissimilarity in outcomes among patients following antihy...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,meta分析
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更新日期:2017-01-01 00:00:00
abstract::Recent results using animal models of inflammatory skin conditions have shown that blockers of the voltage-gated potassium channel, Kv1.3 hold great promise for clinical utility. Kv1.3 blockers act as immunosuppressants by modulating the various subsets of inflammatory T and B cells involved in autoimmune disorders. W...
journal_title:Current medicinal chemistry
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更新日期:2010-01-01 00:00:00
abstract::The discovery of cannabinoid receptors at the beginning of the 1990s, CB1 cloned in 1990 and CB2 cloned in 1993, and the availability of selective and potent cannabimimetics could only be justified by the existence of endogenous ligands that are capable of binding to them. Thus, the characterisation and cloning of the...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2019-01-01 00:00:00