Abstract:
:The OB-receptor or leptin receptor (LR) is crucial for energy homeostasis and regulation of food uptake. Leptin is a 16 kDa hormone that is mainly secreted by fat cells into the bloodstream. Under normal circumstances, circulating leptin levels are proportionate to the fat body mass. Sensing of elevated leptin levels by the hypothalamic neuro-circuitry activates a negative feedback loop resulting in reduced food intake and increased energy expenditure. Decreased leptin concentrations lead to opposite effects. Therefore, rational design of leptin agonists/antagonists could be an appealing challenge in the battle against obesity. The Leptin/LR interactions have been studied in several works by means of different molecular modelling approaches, spreading from homology modelling to manual docking. No small molecules have ever been proposed as agonists of the Ob receptor but researchers' efforts focused only on leptin-related synthetic peptides as receptor antagonists and on peptidomimetics. In this review we try to track a timeline of obtained in silico information to clarify the mechanism of interaction between leptin and its receptor, together to summarize the more recent efforts to propose new drugs usable in anti-obesity therapy. Final considerations could be useful starting points for the rational drug design of new lead compounds.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Tutone M,Lauria A,Almerico AMdoi
10.2174/13816128113196660743subject
Has Abstractpub_date
2014-01-01 00:00:00pages
136-45issue
1eissn
1381-6128issn
1873-4286pii
CPD-EPUB-57056journal_volume
20pub_type
杂志文章,评审abstract::Molecular Mechanics (MM) force fields are the methods of choice for protein simulations, which are essential in the study of conformational flexibility. Given the importance of protein flexibility in drug binding, MM is involved in most if not all Computational Structure-Based Drug Discovery (CSBDD) projects. This pap...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990600
更新日期:2014-01-01 00:00:00
abstract::Introduction of flow cytometric technique to the research on basophil activation has led to significant achievements in allergy diagnosis in vitro. Most of the studies employing the flow cytometry used CD63 as a marker of basophil activation and only some of them used CD203c. Recently discovered basophil activation ma...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211798357890
更新日期:2011-11-01 00:00:00
abstract::Coronary artery disease (CAD) ranks as the leading cause of death in the Western world. The most widely used therapeutics utilized for the treatment of CAD are the lipid-lowering drugs, which lower plasma cholesterol. However lowering cholesterol alone may not be sufficient to provide benefit to all patient population...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:1999-01-01 00:00:00
abstract::CHD is one of the most common serious chronic conditions in postmenopausal women and leads to extremely high risk for recurrent myocardial infarction and death. On the basis of the currently available randomized clinical-trial results the role of conventional HRT for treatment and prevention of CHD is rapidly evolving...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161205774913237
更新日期:2005-01-01 00:00:00
abstract::Current antiretroviral therapy has had a significant impact on HIV associated morbidity and mortality. Despite these positive outcomes current antiretroviral regimens have significant deficiencies which include multiple drug-drug interactions, high pill burdens, and considerable financial expense. Perhaps the greatest...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206776055868
更新日期:2006-01-01 00:00:00
abstract::Alzheimer's disease (AD) is a complex degenerative disorder of the brain, associated with a progressive cognitive decline. Age is the main risk factor with almost half of the population above 90 years affected by this pathology. AD and brain aging share common molecular changes, so it has been hypothesized that AD cou...
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::We set up two models of gastric bleeding in rats using low-dose aspirin (ASA) and the antiplatelet drug clopidogrel, a P2Y₁₂ receptor antagonist, and examined the effect of antiulcer drugs on gastric bleeding and ulcerogenic responses under such conditions. Under urethane anesthesia, two catheters were inserted into t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990418
更新日期:2014-01-01 00:00:00
abstract::Multiple molecular, cellular, structural and functional changes occur in the brain during aging. Neural cells may respond to these changes adaptively by employing multiple mechanisms in order to maintain the integrity of nerve cell circuits and to facilitate responses to environmental demands. Otherwise, they may succ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210790883741
更新日期:2010-01-01 00:00:00
abstract::An integrative synthesis of concepts and an explosion of experimental and epidemiological findings allow new insights as to how the interactions of genetic, environmental, dietary, cultural (social, psychological, economic) factors can influence the aging and diseases of aging processes. Although the net effect of the...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786264106
更新日期:2008-01-01 00:00:00
abstract::Recent decades mark a great progress in the treatment of HIV infection. What was once a deadly disease is now a chronic infection. However, HIV-infected patients are prone to develop comorbidities, which severely affect their daily functions. For example, a large population of patients develop a variety of neurologica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160726113001
更新日期:2016-01-01 00:00:00
abstract::Among pediatric patients, preterm neonates and newborns are the most vulnerable subpopulation. Rapid developmental changes of physiological factors affecting the pharmacokinetics of drug substances in newborns require extreme care in dose and dose regimen decisions. These decisions could be supported by in silico meth...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150901110533
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Arterial hypertension (AH) and peripheral arterial disease (PAD) frequently coincide. While significant attention is paid to AH, PAD is often underestimated. It is known that both AH and PAD present high cardiovascular risks for ischemic events. To date, the use of the most common anti-hypertensive drugs in ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170608083605
更新日期:2017-01-01 00:00:00
abstract::Mitochondria fulfill a number of essential cellular functions, being recognized that the strict regulation of the structure, function and turnover of these organelles is an immutable control node for the maintenance of neuronal integrity and homeostasis. Many lines of evidence posit that mitochondria constitute a conv...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211798072490
更新日期:2011-01-01 00:00:00
abstract::There is extensive evidence that changes in immune system activation accompany the pathological changes of Alzheimer's disease (AD), but a mechanistic understanding of how the immune system actually participates in disease pathogenesis is still largely lacking. Because of the complexity of the immunological response, ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161205774370843
更新日期:2005-01-01 00:00:00
abstract::The vasoconstrictive and antidiuretic physiologic properties of vasopressin (antidiuretic hormone) have long been known. Until recently however, vasopressin was mostly used for diabetes insipidus and noctournal enuresis. This review summarizes the growing body of evidence regarding the perioperative use of vasopressin...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212803832326
更新日期:2012-01-01 00:00:00
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 ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789824786
更新日期:2009-01-01 00:00:00
abstract::Serotonin (5-HT) is one of the main transmitters in the nervous system. Serotonergic neurons in the raphe nuclei in the brainstem innervate most parts of the central nervous system including motoneurons in the spinal cord and brainstem. This review will focus on the modulatory role that 5-HT exerts on motoneurons and ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990341
更新日期:2013-01-01 00:00:00
abstract::Erectile dysfunction (ED) has multifactor pathogenesis, with neurological, vascular, endocrinological and psychogenic components described. However, about 50-85% of ED population report the presence of one or more comorbidities i.e. hypertension, diabetes, cardiovascular disease, dyslipidemia which all impair endothel...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206778343046
更新日期:2006-01-01 00:00:00
abstract::Gene therapy may be capable of treating a variety of diseases, a prerequisite of which is the successful delivery of polynucleic acids (e.g., DNA, RNA) to a patient's cells. Delivery can be achieved technologically (e.g., using electroporation), using viruses (natural gene delivery vectors) or non-viral vectors (e.g.,...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170710124137
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:In the field of forensic toxicology, the quality of analytical methods is of great importance to ensure the reliability of results and to avoid unjustified legal consequences. A key to high quality analytical methods is a thorough method development. METHODS:The presented article will provide an overview on...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170622113331
更新日期:2017-01-01 00:00:00
abstract::Mitochondria are involved in different physiological and pathological processes that are crucial for tumor cell physiology, growth and survival. Since cancer cells have frequently disrupted different cell death pathways that promote their survival, mitochondria may be key organelles to promote cell death in cancer cel...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211796904803
更新日期:2011-01-01 00:00:00
abstract::Severe sepsis leading to shock is the principal cause of death in intensive care units. It is a systemic inflammatory response caused by excessive secretion of pro-inflammatory mediators, such as tumor necrosis factor-alpha (TNFalpha) and reactive oxygen species (ROS), mainly induced by endotoxin (a major component of...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054864894
更新日期:2005-01-01 00:00:00
abstract::The term endozepines designates a family of astroglia-secreted proteins including the diazepambinding inhibitor (DBI) and its processing products, which have been originally isolated and characterized as endogenous ligands of benzodiazepine receptors. It is now clearly established that the octadecaneuropeptide ODN (DB...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666181112111746
更新日期:2018-01-01 00:00:00
abstract::Peroxynitrite, the product of the reaction between nitric oxide and superoxide, is spontaneouly formed within most mammalian cells under physiological conditions. Initial work addressing the pathophysiology of peroxynitrite afforded the generally accepted notion that this compound would be the long-term neurotoxic nit...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043452910
更新日期:2004-01-01 00:00:00
abstract::Fever of Unknown Origin, or FUO, is a challenging condition for patients and clinicians. In up to 50% of cases, no diagnosis is established. Patient workup begins with comprehensive history, physical examination and laboratory tests. Radionuclide imaging has been a second-line procedure. Gallium-67 citrate, which accu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666171129194507
更新日期:2018-01-01 00:00:00
abstract:OBJECTIVES:This paper reviews literary evidence on antithrombotic therapies currently employed in TAVR to assess validity and efficacy; duration and modality are also considered. In the absence of firm guidelines and reliable trial results, we analyze current knowledge of interaction between PPI and antithrombotic drug...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319220002
更新日期:2013-01-01 00:00:00
abstract::Repurposing already approved drugs as new anticancer agents is a promising strategy considering the advantages such as low costs, low risks and less time-consumption. Disulfiram (DSF), as the first drug for antialcoholism, was approved by the U.S. Food and Drug Administration (FDA) over 60 years ago. Increasing eviden...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190816233755
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:In spite of considerable efforts of researchers the cancer deseases remain to be incurable and a percentage of cancer deseases in the structure of mortality increases every year. At that, high systemic toxicity of antitumor drugs hampers their effective use. Because of this fact, the development of nanosyste...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190117095132
更新日期:2018-01-01 00:00:00
abstract::Toll-like receptors (TLRs) have emerged as critical players in immunity. They are capable of sensing organisms ranging from protozoa to bacteria, fungi or viruses upon detection of the pathogen as well as recognizing endogenous ligands, and triggering transduction pathways. Following activation of the innate immune sy...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206778743493
更新日期:2006-01-01 00:00:00
abstract::Mast cells, traditionally regarded as effector cells of the immune system, have more recently been demonstrated to be key figures in initiating, developing and sustaining complex pathophysiological processes underlying asthma and other allergic diseases. Asthma is characterised by airway inflammation alongside a distu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211795428975
更新日期:2011-01-01 00:00:00