Abstract:
:This review will focus on the construction, refinement, and validation of G Protein-coupled receptor models for the purpose of structure-based virtual screening. Practical tips and tricks derived from concrete modeling and virtual screening exercises to overcome the problems and pitfalls associated with the different steps of the receptor modeling workflow will be presented. These examples will not only include rhodopsin-like (class A), but also secretine-like (class B), and glutamate-like (class C) receptors. In addition, the review will present a careful comparative analysis of current crystal structures and their implication on homology modeling. The following themes will be discussed: i) the use of experimental anchors in guiding the modeling procedure; ii) amino acid sequence alignments; iii) ligand binding mode accommodation and binding cavity expansion; iv) proline-induced kinks in transmembrane helices; v) binding mode prediction and virtual screening by receptor-ligand interaction fingerprint scoring; vi) extracellular loop modeling; vii) virtual filtering schemes. Finally, an overview of several successful structure-based screening shows that receptor models, despite structural inaccuracies, can be efficiently used to find novel ligands.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
de Graaf C,Rognan Ddoi
10.2174/138161209789824786subject
Has Abstractpub_date
2009-01-01 00:00:00pages
4026-48issue
35eissn
1381-6128issn
1873-4286journal_volume
15pub_type
杂志文章,评审abstract::The CCN family of growth factors is composed of six structurally related proteins including the cysteine-rich 61 (Cyr61), connective tissue growth factor (CTGF), nephroblastoma overexpressed (NOV), Wnt-1 induced secreted protein-1 (WISP-1), WISP-2 and WISP-3. Each family member consists of four conserved cysteine rich...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043382567
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Psoriasis is an autoimmune disease of the skin with lapsing episodes of hyperkeratosis, irritation and inflammation. Numerous methodologies and utilization of different antipsoriatic drugs with various activity methods and routes of administration have been investigated to treat this terrifying sickness. In ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666181102151507
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Hepatocellular carcinoma (HCC) has high mortality partly due to acquiring drug resistance during chemotherapy treatment. Therefore, it is necessary to explore the underlying mechanism of drug resistance. METHODS:We used 2-DE and MALDI-TOF-MS analysis to explore the possible molecular insight into 5-FU resis...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161282001140113125143
更新日期:2014-01-01 00:00:00
abstract::1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly(ethylene glycol) (DSPE- PEG) is a widely used phospholipids-polymer conjugate in drug delivery applications. It is a biocompatible, biodegradable and amphiphilic material which can also be functionalized with various biomolecules for specific functions. With the em...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150115144003
更新日期:2015-01-01 00:00:00
abstract::"Molecular recognition" is one of the most important molecular processes for living systems in order to maintain their life, since most of the biological functions are initiated with the process. Understanding of the process is also important for designing a new drug. Firstly, it is important to find a target of a dru...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211796355100
更新日期:2011-01-01 00:00:00
abstract::The cytokine tumor necrosis factor(alpha) (TNF(alpha)) is associated with a constellation of physiological and behavioral characteristics that follow in response to infection such as fever, fatigue, listlessness, loss of appetite, malaise, and tactile hypersensitivity. These responses are examples of central nervous s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053507828
更新日期:2005-01-01 00:00:00
abstract::Phytoestrogens are plant-derived compounds with estrogen-like activities. Certain foods such as soy-derived products are known to have high levels of phytoestrogens, and about 25% of commercial infant formulas used in the United States are soy-based. One of the most important phytoestrogens is the isoflavone genistein...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043383683
更新日期:2004-01-01 00:00:00
abstract::The current gold standard for imaging infection is radiolabeled white blood cells. For reasons of safety, simplicity and cost, it would be desirable to have a receptor-specific ligand that could be used for imaging infection and that would allow a differential diagnosis between sterile and septic inflammatory processe...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786549416
更新日期:2008-01-01 00:00:00
abstract::Single-agent therapy with molecularly targeted agents has shown limited success in tumor growth control, mainly because escape or resistance mechanisms are activated once a signalling molecule is inhibited. Rational combinations of target-specific agents could counteract this response providing a useful strategy in ca...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:The objective of this study was to apply Quality by Design (QbD) principles on process parameter optimization for the development of hybrid delivery system (combination of (SLNs) and In-situ gelling system) for hydrophilic drug Moxifloxacin Hydrochloride (MOX) to achieve its controlled delivery, which otherw...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612824666180403115106
更新日期:2018-01-01 00:00:00
abstract::Nonalcoholic fatty liver disease (NAFLD) affects about 20%-30% of the general population, and its clinical relevance arises from the fact that 20%-30% of these subjects develop non-alcoholic steatohepatitis (NASH), a condition at risk of cirrhosis progression. In addition NAFLD, and in particular NASH patients, are al...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::The large conduit arteries of the thorax and abdomen are elastic while those in the arms and legs are muscular. Alterations in wall properties of elastic arteries occur over time and are usually permanent in nature; acute changes can, however, occur is response to a change in transmural pressure. Chronic alterations i...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787354258
更新日期:2009-01-01 00:00:00
abstract::High molecular weight kininogen (HK) is a plasma protein that is cleaved by plasma kallikrein in the clinical settings of sepsis and chronic inflammatory diseases such as rheumatoid arthritis and Crohn's disease. This proteolytic event results in a nonapeptide, bradykinin (BK), and a kinin-free derivative of HK, namel...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777698710
更新日期:2006-01-01 00:00:00
abstract::Active pharmaceutical ingredients (APIs) can exist in different polymorphic forms as well as in amorphous state. Polymorphic and amorphous forms of APIs can differ in physicochemical properties which in turn can significantly influence their therapeutic safety and effectiveness of the treatment. This review focuses on...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160804100036
更新日期:2016-01-01 00:00:00
abstract::Opioids remain the standard of care in the provision of analgesia in the patient undergoing cancer surgery preoperatively. The effects of opioids on tumor growth and metastasis have been discussed for many years. In recent years their use as part of the perioperative pain management bundle in the patients undergoing c...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190703163329
更新日期:2019-01-01 00:00:00
abstract::Synaptic transmission through descending motor pathways to lumbar motoneurons and then to leg muscles is essential for walking in humans and rats. Spinal cord injury (SCI), even when incomplete, results in diminished transmission to motoneurons and very limited recovery of motor function. Neurotrophins have emerged as...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990378
更新日期:2013-01-01 00:00:00
abstract::Chemokines and their receptors play critical roles in leukocyte trafficking during inflammatory processes. Although the role of chemokine receptors (CKRs) in cancer biology is a relatively new field of study, a growing body of data suggest that a number of CKRs, including CXCR4, CCR4, CCR7, and CCR10, may play diverse...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787582165
更新日期:2009-01-01 00:00:00
abstract::Colchicine is a lipophilic alkaloid drug, which exhibits ant-inflammatory and anti-fibrotic properties. Cardinal mechanisms of action of colchicine are the disruption of the microtubule system and the inhibition of neutrophil adhesion and recruitment. Colchicine is indicated in the prevention and treatment of gouty ar...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180123101313
更新日期:2018-01-01 00:00:00
abstract::DNA methylation is an important regulatory component which influences phenotypes by modulating gene expression. Changes in DNA methylation may lead to altered phenotypes and ability of an organism to respond to stress leading to subsequent manifestation of life style diseases, cancer, etc. The human X chromosome repre...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990518
更新日期:2014-01-01 00:00:00
abstract::Since the first description of putative progenitor endothelial cells mobilized from bone marrow by stimuli like ischemia and cytokines, several studies in animals have confirmed their role in neovascularization of ischemic organs. In ischemic myocardium endothelial progenitor cells can prevent cardiomyocyte apoptosis,...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207780831329
更新日期:2007-01-01 00:00:00
abstract::Aspirin is an antiplatelet drug, inhibiting the cyclooxygenase activity of platelet prostaglandin H synthase-1 and almost complete suppressing platelet capacity to generate the prothrombotic and proatherogenic thromboxane A2. Antiplatelet therapy with aspirin reduces the risk of serious vascular events by about a quar...
journal_title:Current pharmaceutical design
pub_type: 历史文章,杂志文章,评审
doi:10.2174/138161212803251943
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Atherosclerosis is a chronic inflammatory disease and a leading cause of coronary artery disease, peripheral vascular disease and stroke. Lipid-laden macrophages are derived from circulating monocytes and form fatty streaks as the first step of atherogenesis. METHODS:An electronic search in major databases ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190830153056
更新日期:2019-01-01 00:00:00
abstract::Angiogenic eye disease is among the most common causes of blindness worldwide. Current treatment approaches are insufficiently effective and partially associated with significant adverse effects. From an investigational view, the eye provides an ideal setting to observe real-time and serial observations of angiogenesi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054367292
更新日期:2005-01-01 00:00:00
abstract::P-Glycoprotein (P-gp) is a 170-kDa transmembrane glycoprotein that works as an efflux pump and confers multidrug resistance (MDR) in normal tissues and tumors, including nervous tissues and brain tumors. In the developing telencephalon, the endothelial expression of P-gp, and the subcellular localization of the transp...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200318130625
更新日期:2020-01-01 00:00:00
abstract::The comorbid prevalence of major depressive disorder (MDD) with obesity and type II diabetes mellitus reflects the existence of a subset of individuals with a complex common pathophysiology and overlapping risk factors. Such comorbid disease presentations imply a number of difficulties, including: decreased treatment ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160922165706
更新日期:2016-01-01 00:00:00
abstract::Growth and metastasis of lung cancer requires a sequence of events, which alter the ability of neoplastic cells to adhere to themselves, to normal surrounding cells, or to the extracellular matrix. Interactions between cells are primarily mediated by four types of structures in the plasma membrane: gap junctions, tigh...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208785740162
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:According to the World Health Organization (WHO), diabetes mellitus is considered the 7th leading cause of death as of 2016, while almost half of all deaths related to high blood glucose occur before the age of 70. According to the 2019 American Diabetes Association's (ADA) guidelines, metformin is the first...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200408095310
更新日期:2020-01-01 00:00:00
abstract::Early life stress is considered a risk factor for the development of many diseases in both adolescence and adulthood. It has been reported that chronic stress (for instance, due to maternal separation during breast feeding), causes damage to the central nervous system at the level of neurons and glial cells, which are...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170224111641
更新日期:2018-02-12 00:00:00
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
更新日期:2009-01-01 00:00:00
abstract::Unhealthy diet and alcohol are serious health problems, especially in adolescents and young adults. "Binge" is defined as the excessive and uncontrolled consumption of food (binge eating) and alcohol (binge drinking). Both behaviors are frequent among young people and have a highly negative impact on health and qualit...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200316153317
更新日期:2020-01-01 00:00:00