Melanin-concentrating hormone receptor 1 antagonists: a new perspective for the pharmacologic treatment of obesity.

Abstract:

:Obesity is a chronic disease characterized by the accumulation of excess adipose tissue associated with an increased risk of multiple morbidities and mortality. At the present time, only three drugs have been approved by the Food and Drug Administration (FDA) for the treatment of obesity. Agonists and antagonists of some of the substances implicated in the regulation of energy homeostasis represent opportunities for anti-obesity drug development. The most promising targets are alpha-melanocyte stimulating hormone (alpha-MSH) receptors, cannabinoid receptors, the 5-hydroxytryptamine (5-HT) receptors and melanin-concentrating hormone (MCH) receptors. MCH receptors could be major potential targets for the treatment of obesity. Many pharmaceutical companies have described MCH-R1 antagonists that have appeared over the past year. Recently, two compounds went into phase I clinical trials that evaluate MCH receptor antagonists as a new perspective for the pharmacologic treatment of obesity. In this review, structure-activity relationships (SAR) in the development of MCH-R1 antagonists are provided.

journal_name

Curr Med Chem

authors

Rivera G,Bocanegra-García V,Galiano S,Cirauqui N,Ceras J,Pérez S,Aldana I,Monge A

doi

10.2174/092986708784049621

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

1025-43

issue

10

eissn

0929-8673

issn

1875-533X

journal_volume

15

pub_type

杂志文章,评审
  • The atherosclerotic plaque vulnerability: focus on the oxidative and endoplasmic reticulum stress in orchestrating the macrophage apoptosis in the formation of the necrotic core.

    abstract::Although the understanding the pathophysiology of atherogenesis and atherosclerosis progression has been one of the major goals of cardiovascular research during the last decades, the precise mechanisms underlying plaque destabilization are still unknown. The disruption of the plaque and the thrombosis in the lumen th...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867322666150311150829

    authors: Cominacini L,Garbin U,Mozzini C,Stranieri C,Pasini A,Solani E,Tinelli IA,Pasini AF

    更新日期:2015-01-01 00:00:00

  • Multi-aspect candidates for repositioning: data fusion methods using heterogeneous information sources.

    abstract::Drug repositioning, an innovative therapeutic application of an old drug, has received much attention as a particularly costeffective strategy in drug R&D Recent work has indicated that repositioning can be promoted by utilizing a wide range of information sources, including medicinal chemical, target, mechanism, main...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章

    doi:

    authors: Arany Á,Bolgár B,Balogh B,Antal P,Mátyus P

    更新日期:2013-01-01 00:00:00

  • On the physiological role of cytosolic 5'-nucleotidase II (cN-II): pathological and therapeutical implications.

    abstract::Among the members of the 5'-nucleotidase family, there is only one membrane-bound ectosolic isoenzyme. This esterase prefers AMP as substrate but can hydrolyze a number of purine and pyrimidine phosphorylated compounds, indicating that no evolutive pressure to develop a more restricted specificity was exerted on this ...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867311320340007

    authors: Tozzi MG,Pesi R,Allegrini S

    更新日期:2013-01-01 00:00:00

  • Molecular Design and Medicinal Applications of Nano-Nitric Oxide Delivery Systems.

    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

    pub_type: 杂志文章,评审

    doi:10.2174/0929867324666170407141222

    authors: Nguyen KT,Wu Z,Huang T,Tay CY

    更新日期:2018-01-01 00:00:00

  • Bio-inspired algorithms applied to molecular docking simulations.

    abstract::Nature as a source of inspiration has been shown to have a great beneficial impact on the development of new computational methodologies. In this scenario, analyses of the interactions between a protein target and a ligand can be simulated by biologically inspired algorithms (BIAs). These algorithms mimic biological s...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986711795029573

    authors: Heberlé G,de Azevedo WF Jr

    更新日期:2011-01-01 00:00:00

  • Synthesis and biological activity of phosphonated nucleosides: part 1. Furanose, carbocyclic and heterocyclic analogues.

    abstract::Phosphonated nucleosides represent a promising alternative in the improvement of the biological activity of nucleoside analogues in antiviral and anticancer chemotherapy. The basic concept, the chemistry, the different structural modifications and their effects on the antiviral potency will be discussed in this review...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986706779026110

    authors: Piperno A,Chiacchio MA,Iannazzo D,Romeo R

    更新日期:2006-01-01 00:00:00

  • Development and application of Fourier-transform infrared chemical imaging of tumour in human tissue.

    abstract::Fourier-transform infrared (FT-IR) based mapping and imaging is a fast emerging technology which is being increasingly applied to investigate tissues in the high-throughput mode. The high resolution close to the cellular level, the possibility to determine the bio-distribution of molecules of interest (proteins, pepti...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986709787002664

    authors: Petter CH,Heigl N,Rainer M,Bakry R,Pallua J,Bonn GK,Huck CW

    更新日期:2009-01-01 00:00:00

  • Structural approaches to explain the selectivity of COX-2 inhibitors: is there a common pharmacophore?

    abstract::The identification and characterisation of the isoenzyme cyclooxygenase 2 (COX-2) stimulated investigations to develop efficient non-steroidal anti-inflammatory drugs with reduced side effects compared to standard NSAIDs. This review will focus on the structural features needed to achieve COX-2 selectivity. Five struc...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867003374237

    authors: Dannhardt G,Laufer S

    更新日期:2000-11-01 00:00:00

  • Progress in COX-2 inhibitors: a journey so far.

    abstract::The non-steroidal anti-inflammatory drugs (NSAIDs) are diverse group of compounds used for the treatment of inflammation, since the introduction of acetylsalicylic acid in 1899. Traditional (first generation) NSAIDs exert antiinflammatory, analgesic, and antipyretic effects through the blockade of prostaglandin synthe...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986710790979980

    authors: Chakraborti AK,Garg SK,Kumar R,Motiwala HF,Jadhavar PS

    更新日期:2010-01-01 00:00:00

  • Thrombomodulin--a new target for treating stroke at the crossroad of coagulation and inflammation.

    abstract::Thrombomodulin (TM) is a membrane protein mainly expressed by endothelial cells. It is part of the anticoagulant protein C system but recently several effects were discovered which occur independently of protein C activation. TM binds thrombin and promotes the cleavage of protein C and the thrombin activatable fibrino...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867321666131228204839

    authors: Wenzel J,Assmann JC,Schwaninger M

    更新日期:2014-01-01 00:00:00

  • Toxins from Physalia physalis (Cnidaria) raise the intracellular Ca(2+) of beta-cells and promote insulin secretion.

    abstract::Physalia physalis is a marine cnidarian from which high molecular weight toxins with hemolytic and neurotoxic effects have been isolated. In the present work, two novel toxins, PpV9.4 and PpV19.3 were purified from P. physalis by bioactive guideline isolation. It involved two steps of column chromatography, gel filtra...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章

    doi:10.2174/092986712803833308

    authors: Diaz-Garcia CM,Fuentes-Silva D,Sanchez-Soto C,Domínguez-Pérez D,García-Delgado N,Varela C,Mendoza-Hernández G,Rodriguez-Romero A,Castaneda O,Hiriart M

    更新日期:2012-01-01 00:00:00

  • Recent chemical and enzymatic approaches to the synthesis of glycosaminoglycan oligosaccharides.

    abstract::Glycosaminoglycans, highly charged polycarboxylated, polysulfated polysaccharides, are an important class of therapeutic agents and investigational drug candidates. Heparin has been widely used as a clinical anticoagulant for over 60 years. Low molecular weight heparins have begun to displace heparin and recently a sy...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867033456891

    authors: Karst NA,Linhardt RJ

    更新日期:2003-10-01 00:00:00

  • Myeloperoxidase as a Target for the Treatment of Inflammatory Syndromes: Mechanisms and Structure Activity Relationships of Inhibitors.

    abstract::Inflammation is an initial response of the body to a harmful stimuli and it is achieved by the increased movement of leukocytes (especially granulocytes) from blood into injured tissues. It is required for healing wounds and infections. Despite their indispensable role in microbial killing, the inflammation reactions ...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867323666160607111806

    authors: Soubhye J,Aldib I,Delporte C,Prévost M,Dufrasne F,Antwerpen PV

    更新日期:2016-01-01 00:00:00

  • Aptamers as therapeutics in cardiovascular diseases.

    abstract::With many advantages over other therapeutic agents such as monoclonal antibodies, aptamers have recently emerged as a novel and powerful class of ligands with excellent potential for diagnostic and therapeutic applications. Typically generated through Systematic Evolution of Ligands by EXponential enrichment (SELEX), ...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986711797189673

    authors: Wang P,Yang Y,Hong H,Zhang Y,Cai W,Fang D

    更新日期:2011-01-01 00:00:00

  • Molecular and biochemical features of the mitochondrial enzyme ornithine transcarbamylase: a possible new role as a signaling factor.

    abstract::Ornithine transcarbamylase (OTC; EC 2.1.3.3) is a one-carbon-unit transferring enzyme that synthesizes citrulline using ornithine and carbamoylphosphate as substrates. It is involved in the metabolic transformation of arginine and proline, and it participates in the urea cycle in vertebrates and in the formation of pu...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986710791331031

    authors: Díaz-Muñoz M,Hernández-Muñoz R

    更新日期:2010-01-01 00:00:00

  • Stimuli-responsive Carriers for Controlled Intracellular Drug Release.

    abstract:BACKGROUND:Stimuli-responsive carriers are a class of drug delivery systems which can change their physicochemical properties and/or structural conformations in response to specific stimuli. Although passive and active drug targeting has proved to reduce the side effects to normal cells, controlled intracellular drug r...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867324666170830102409

    authors: Sheng Y,Hu J,Shi J,Lee LJ

    更新日期:2019-01-01 00:00:00

  • Advances in parallel screening of drug candidates.

    abstract::In the hit to lead process, a drug candidate is selected from a set of potential leads by screening its binding with potential targets. This review focuses on the lead identification assays that employ a bio-chemical or bio-physical test to detect molecular recognition events between proteins and small molecules in a ...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986708784872366

    authors: Bergese P,Cretich M,Oldani C,Oliviero G,Di Carlo G,Depero LE,Chiari M

    更新日期:2008-01-01 00:00:00

  • Advances in metal-based probes for MR molecular imaging applications.

    abstract::The role of MRI in the armory of diagnostic modalities for the medicine of the forthcoming years largely depends on how chemistry will provide advanced tools to meet the medical needs. This review aims at outlining the most innovative approaches that have been undertaken in the recent history of MRI contrast agents fo...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986710793213823

    authors: Terreno E,Dastrù W,Delli Castelli D,Gianolio E,Geninatti Crich S,Longo D,Aime S

    更新日期:2010-01-01 00:00:00

  • Mechanism of organophosphates (nerve gases and pesticides) and antidotes: electron transfer and oxidative stress.

    abstract::Evidence indicates that nerve gas toxins operate in ways in addition to inhibition of acetylcholine esterase. Alternative bioactivities are discussed with focus on electron transfer. The main class, including pralidoxime (2-PAM), incorporates conjugated iminium and oxime moieties that are electron affinic. Various phy...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867033456314

    authors: Kovacic P

    更新日期:2003-12-01 00:00:00

  • High Resolution Nuclear Magnetic Resonance Spectroscopy on Biological Tissue and Metabolomics.

    abstract::High-resolution nuclear magnetic resonance (NMR) spectroscopy is a universal analytical tool. It can provide detailed information on chemical shifts, J coupling constants, multiplet patterns, and relative peak areas. It plays an important role in the fields of chemistry, biology, medicine, and pharmacy. A highly homog...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867326666190312130155

    authors: Lin Y,Zeng Q,Lin L,Chen Z

    更新日期:2019-01-01 00:00:00

  • The palmitoylethanolamide and oleamide enigmas : are these two fatty acid amides cannabimimetic?

    abstract::Palmitoylethanolamide (PEA) and oleamide are two fatty acid amides which 1) share some cannabimimetic actions with delta9-tetrahydrocannabinol, anandamide and 2-arachidonoylglycerol, and 2) may interact with proteins involved in the biosynthesis, action and inactivation of endocannabinoids. Due to its pharmacological ...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:

    authors: Lambert DM,Di Marzo V

    更新日期:1999-08-01 00:00:00

  • Antipsychotic and antiepileptic drugs in bipolar disorder: the importance of therapeutic drug monitoring.

    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

    pub_type: 杂志文章,评审

    doi:10.2174/092986709787909604

    authors: Musenga A,Saracino MA,Sani G,Raggi MA

    更新日期:2009-01-01 00:00:00

  • Monoclonal antibody "gold rush".

    abstract::The market, sales and regulatory approval of new human medicines, during the past few years, indicates increasing number and share of new biologics and emergence of new multibillion dollar molecules. The global sale of monoclonal antibodies in 2006 were $20.6 billion. Remicade had annual sales gain of $1 billion durin...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986707781368504

    authors: Maggon K

    更新日期:2007-01-01 00:00:00

  • Therapeutic Macromolecular Iron Chelators.

    abstract::Iron is a key element for every single living process. On a fundamental level, targeting iron is a valuable approach for the treatment of disorders caused by iron overload. Utilizing iron chelators as therapeutic agents has received expanding consideration in chelation therapy. Approved low molecular weight (MW) iron ...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章

    doi:10.2174/0929867325666180904104318

    authors: Bulbake U,Singh A,Domb AJ,Khan W

    更新日期:2019-01-01 00:00:00

  • Mechanisms of resistance to photodynamic therapy.

    abstract::Photodynamic therapy (PDT) involves the administration of a photosensitizer (PS) followed by illumination with visible light, leading to generation of reactive oxygen species. The mechanisms of resistance to PDT ascribed to the PS may be shared with the general mechanisms of drug resistance, and are related to altered...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986711795843272

    authors: Casas A,Di Venosa G,Hasan T,Al Batlle

    更新日期:2011-01-01 00:00:00

  • Functional, genetic and biochemical biomarkers of peripheral arterial disease.

    abstract::Patients with peripheral arterial disease (PAD) suffer from increased cardiovascular morbidity and mortality. The ankle brachial index has been widely used as an easy tool to identify and stratify patients with PAD, however its predictive value remains limited. Higher levels of inflammatory and prothrombotic biomarker...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/092986712800492959

    authors: Charakida M,Masi S,Tousoulis D

    更新日期:2012-01-01 00:00:00

  • Biological and chemical diversity of coral-derived microorganisms.

    abstract::Coral-derived microorganisms have been a major focus of many research efforts on marine ecology in recent decades. Importantly, research on bioactive compounds from these diverse microorganisms, which include fungi and bacteria, has experienced an explosive growth during the past five years. This has unveiled the ecol...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867322666151006093755

    authors: Hou XM,Xu RF,Gu YC,Wang CY,Shao CL

    更新日期:2015-01-01 00:00:00

  • Convolutional Neural Network Based Virtual Screening.

    abstract::Virtual screening is an important means for lead compound discovery. The scoring function is the key to selecting hit compounds. Many scoring functions are currently available; however, there are no all-purpose scoring functions because different scoring functions tend to have conflicting results. Recently, neural net...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章

    doi:10.2174/0929867327666200526142958

    authors: Shan W,Li X,Yao H,Lin K

    更新日期:2020-05-26 00:00:00

  • Possible Molecular Mechanisms by which Vitamin D Prevents Inflammatory Bowel Disease and Colitis-associated Colorectal Cancer.

    abstract::It is well accepted that inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is one of high risk factors for colorectal cancer (CRC). This supports the notion that inflammation plays a key role in cancer development. Epidemiologic studies have shown that vitamin D (Vit D) deficiency is ...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章

    doi:10.2174/0929867323666161202153028

    authors: Luan Z,Ma Y,Xin Y,Qian J,Wang H

    更新日期:2017-01-01 00:00:00

  • Torsadogenic cardiotoxicity of antipsychotic drugs: a structural feature, potentially involved in the interaction with cardiac HERG potassium channels.

    abstract::Many non-cardiovascular drugs of common clinical use cause, as an unwanted accessory property, the prolongation of the cardiac repolarisation process, due to the block of the HERG (Human Ether-a-go-go Related Gene) potassium channel, responsible for the repolarising I(Kr) current. This delayed cardiac repolarisation p...

    journal_title:Current medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.2174/0929867043364351

    authors: Testai L,Bianucci AM,Massarelli I,Breschi MC,Martinotti E,Calderone V

    更新日期:2004-10-01 00:00:00