Leptin and the OB-receptor as anti-obesity target: recent in silico advances in the comprehension of the protein-protein interaction and rational drug design of anti- obesity lead compounds.

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 Des

authors

Tutone M,Lauria A,Almerico AM

doi

10.2174/13816128113196660743

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

136-45

issue

1

eissn

1381-6128

issn

1873-4286

pii

CPD-EPUB-57056

journal_volume

20

pub_type

杂志文章,评审
  • Molecular mechanics.

    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

    authors: Vanommeslaeghe K,Guvench O,MacKerell AD Jr

    更新日期:2014-01-01 00:00:00

  • CD164 as a Basophil Activation Marker.

    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

    authors: Wolanczyk-Medrala A,Barg W,Medrala W

    更新日期:2011-11-01 00:00:00

  • Therapeutic strategies for coronary artery disease beyond low density lipoprotein (LDL)--lowering.

    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:

    authors: Arad Y,Saxena U

    更新日期:1999-01-01 00:00:00

  • Raloxifene and cardiovascular health: its relationship to lipid and glucose metabolism, hemostatic and inflammation factors and cardiovascular function in postmenopausal women.

    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

    authors: Francucci CM,Camilletti A,Boscaro M

    更新日期:2005-01-01 00:00:00

  • Use of virostatics as a means of targeting human immunodeficiency virus infection.

    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

    authors: Romanelli F,Hoven AD

    更新日期:2006-01-01 00:00:00

  • Platelets in Alzheimer's disease-associated cellular senescence and inflammation.

    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:

    authors: Casoli T,Balietti M,Giorgetti B,Solazzi M,Scarpino O,Fattoretti P

    更新日期:2013-01-01 00:00:00

  • Animal models of gastric bleeding induced by dual antiplatelet therapy using aspirin and clopidogrel--prophylactic effect of antiulcer drugs.

    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

    authors: Takeuchi K,Izuhara C,Takayama S,Momode T,Kojo M,Hara D,Amagase K

    更新日期:2014-01-01 00:00:00

  • The expanding universe of neurotrophic factors: therapeutic potential in aging and age-associated disorders.

    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

    authors: Lanni C,Stanga S,Racchi M,Govoni S

    更新日期:2010-01-01 00:00:00

  • Role of diet and nutrition on the alteration of the quality and quantity of stem cells in human aging and the diseases of aging.

    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

    authors: Trosko JE

    更新日期:2008-01-01 00:00:00

  • Solving the Blood-Brain Barrier Challenge for the Effective Treatment of HIV Replication in the Central Nervous System.

    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

    authors: Bertrand L,Nair M,Toborek M

    更新日期:2016-01-01 00:00:00

  • Development of a Physiologically-Based Pharmacokinetic Model for Preterm Neonates: Evaluation with In Vivo Data.

    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

    authors: Claassen K,Thelen K,Coboeken K,Gaub T,Lippert J,Allegaert K,Willmann S

    更新日期:2015-01-01 00:00:00

  • How to Treat Patients with Essential Hypertension and Peripheral Arterial Disease.

    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

    authors: Signorelli SS

    更新日期:2017-01-01 00:00:00

  • New insights into the mechanisms of mitochondrial preconditioning-triggered neuroprotection.

    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

    authors: Correia SC,Cardoso S,Santos RX,Carvalho C,Santos MS,Perry G,Smith MA,Moreira PI

    更新日期:2011-01-01 00:00:00

  • The dualistic nature of immune modulation in Alzheimer's disease: lessons from the transgenic models.

    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

    authors: Nelson RB

    更新日期:2005-01-01 00:00:00

  • Recent advances in perioperative anesthetic management update on the role of vasopressin and its effects on outcomes.

    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

    authors: Udeh CI,Diaz-Gómez JL,Anthony D,Satyapriya A,Perez-Protto S,Hata JS

    更新日期:2012-01-01 00:00:00

  • Customizing G Protein-coupled receptor models for structure-based virtual screening.

    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

    authors: de Graaf C,Rognan D

    更新日期:2009-01-01 00:00:00

  • Modulation of the intrinsic properties of motoneurons by serotonin.

    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

    authors: Perrier JF,Rasmussen HB,Christensen RK,Petersen AV

    更新日期:2013-01-01 00:00:00

  • Phosphodiesterase 5 inhibitors in the treatment of erectile dysfunction.

    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

    authors: Aversa A,Bruzziches R,Pili M,Spera G

    更新日期:2006-01-01 00:00:00

  • Gene Delivery with Organic Electronic Biomaterials.

    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

    authors: Clancy KFA,Hardy JG

    更新日期:2017-01-01 00:00:00

  • Method Development in Forensic Toxicology.

    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

    authors: Peters FT,Wissenbach DK,Busardo FP,Marchei E,Pichini S

    更新日期:2017-01-01 00:00:00

  • Mitochondrial drug targets in cell death and cancer.

    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

    authors: Ferrín G,Linares CI,Muntané J

    更新日期:2011-01-01 00:00:00

  • Role of free radicals in sepsis: antioxidant therapy.

    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

    authors: Victor VM,Rocha M,Esplugues JV,De la Fuente M

    更新日期:2005-01-01 00:00:00

  • Neuroprotection with the Endozepine Octadecaneuropeptide, ODN.

    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

    authors: Masmoudi-Kouki O,Hamdi Y,Ghouili I,Bahdoudi S,Kaddour H,Leprince J,Castel H,Vaudry H,Amri M,Vaudry D,Tonon MC

    更新日期:2018-01-01 00:00:00

  • Provoking neuroprotection by peroxynitrite.

    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

    authors: Bolanos JP,García-Nogales P,Almeida A

    更新日期:2004-01-01 00:00:00

  • Nuclear Medicine Imaging in Fever of Unknown Origin: The New Paradigm.

    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

    authors: Palestro CJ,Love C

    更新日期:2018-01-01 00:00:00

  • Clopidogrel, aspirin and proton pump inhibition after percutaneous valve implants: an update.

    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

    authors: Fusari M

    更新日期:2013-01-01 00:00:00

  • An Updated Review of Disulfiram: Molecular Targets and Strategies for Cancer Treatment.

    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

    authors: Yang Q,Yao Y,Li K,Jiao L,Zhu J,Ni C,Li M,Dou QP,Yang H

    更新日期:2019-01-01 00:00:00

  • Carbon Nanotubes as A High-Performance Platform for Target Delivery of Anticancer Quinones.

    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

    authors: Grushevskaya HV,Krylova NG

    更新日期:2018-01-01 00:00:00

  • Toll-like receptors in human infectious diseases.

    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

    authors: de la Barrera S,Alemán M,Sasiain Mdel C

    更新日期:2006-01-01 00:00:00

  • The role of mast cells in the structural alterations of the airways as a potential mechanism in the pathogenesis of severe asthma.

    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

    authors: Carter RJ,Bradding P

    更新日期:2011-01-01 00:00:00