Abstract:
:The hypothesis that the interaction of agouti-related protein (AGRP) and the melanocortin-4 receptor (MC4R) modulates feeding behavior in humans has stimulated the synthesis of conformationally constrained peptides, peptoids and small molecules in efforts to identify novel compounds that can potentially be used in the clinical treatment of obesity and related eating disorders. In addition, the availability of a high-resolution NMR structure for the MC4R-binding domain of AGRP, and studies employing site-specific murine MC4R mutants have identified key intermolecular AGRP/MC4R interactions. It is therefore surprising that only one, relatively unsophisticated, computer-based study has been reported to obtain a model for the AGRP/mMC4R complex. In this review we outline computer-based strategies for building models of the AGRP/mMC4R and related peptide/mMC4R complexes, and illustrate the strengths and limitations of sophisticated molecular dynamics methods in obtaining information that might form the basis of rational efforts to discover novel drugs that selectively interact with melanocortin receptors.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Wang X,Richards NGdoi
10.2174/1381612053382188subject
Has Abstractpub_date
2005-01-01 00:00:00pages
345-56issue
3eissn
1381-6128issn
1873-4286journal_volume
11pub_type
杂志文章,评审abstract::In the third millennium preventive medicine is becoming a corner stone in our concept of health. Colorectal cancer (CRC) fits the criteria of a disease suitable for prevention interventions. It is a prevalent disease that is associated with considerable mortality and morbidity rates, with more than 1,000,000 new cases...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207781368783
更新日期:2007-01-01 00:00:00
abstract::Monoclonal antibodies have undergone a radical evolutionary journey over the last 25 years, with advances in molecular biology, process development and drug formulation underpinning their rise to becoming one of the most efficacious and economically important class of drug today. The success of antibodies for the trea...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150310142202
更新日期:2015-01-01 00:00:00
abstract::We have synthesized a novel series of N-substituted sarcosines, analogues of NFPS (N-[3-(biphenyl-4- yloxy)-3-(4-fluorophenyl)propyl]-N-methylglycine), as type-1 glycine transporter (GlyT-1) inhibitors. Several compounds incorporated a diazine ring inhibited recombinant hGlyT-1b expressed permanently in CHO cells and ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612821666150109125623
更新日期:2015-01-01 00:00:00
abstract::We illustrate the use of quantitative proteomics, namely isotope-coded affinity tag labelling and tandem mass spectrometry, to assess the targets and effects of the blockade of matrix metalloproteinases by an inhibitor drug in a breast cancer cell culture system. Treatment of MT1-MMP-transfected MDA-MB-231 cells with ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207779313524
更新日期:2007-01-01 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::Cathepsin K, a cysteine protease of the papain family, was identified by sequencing complementary DNA libraries derived from osteoclasts. Cathepsin K can cleave bone proteins such as Type I collagen, osteopontin, and osteonectin. The localization and maturation of cathepsin K in activated osteoclasts have been charact...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003401569
更新日期:2000-01-01 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::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: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::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::Telomerase is a specialized enzymatic complex responsible for the synthesis of telomeric repeats 5'-TTAGGG-3' localized at the ends of eukaryotic chromosomes. This mechanism prevents shortening of telomeres after each cell division. The enzyme is detected in about 85% of human tumors, but it is not expressed in normal...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140630092721
更新日期:2014-01-01 00:00:00
abstract::The formation of liposomes, nanoparticle micelles, and related systems by mixtures of drugs and/or surfactants is of major relevance for the design of drug delivery systems. We can design new systems using different compounds. Traditionally these systems are created by trial and error using experimental data. However,...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160513150054
更新日期:2016-01-01 00:00:00
abstract::Over the last 15 years, the use of various biological therapies has largely improved the way we manage patients with Inflammatory Bowel Diseases (IBDs). Blockade of cytokine synthesis and/or activity is at the forefront of this new era with the success of inhibitors of tumor necrosis factor (TNF)-α. These therapies ar...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210794079164
更新日期:2010-01-01 00:00:00
abstract::The snake is the symbol of medicine due to its association with Asclepius, the Greek God of medicine, and so with good reasons. More than 725 species of venomous snakes have toxins specifically evolved to exert potent bioactivity in prey or victims, and snakebites constitute a public health hazard of high impact in As...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160623073438
更新日期:2016-01-01 00:00:00
abstract::Parkinson's disease (PD) is a movement disorder caused by degeneration of the nigrostriatal dopamine (DA) neurons in the substantia nigra pars compacta and the resultant deficiency in the neurotransmitter DA at the nerve terminals in the striatum. We and other investigators found increased levels of pro-inflammatory c...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053381620
更新日期:2005-01-01 00:00:00
abstract::The pharmacophore concept is central to the rational drug design and discovery process. Traditionally, a pharmacophore is defined as a specific three-dimensional (3D) arrangement of chemical functional groups found in active molecules, which are characteristic of a certain pharmacological class of compounds. Herein, b...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612013397834
更新日期:2001-05-01 00:00:00
abstract:BACKGROUND:A substantial part of literature has been centered on sex differences in the clinical aspects of ischemic heart disease (IHD). Many reports have documented differences in the presentation and risk profile between women and men. Such differences drive sex-related inequalities in the referral and treatment of ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160311115344
更新日期:2016-01-01 00:00:00
abstract::The rapid advancement of computer architectures and development of mathematical algorithms offer a unique opportunity to leverage the simulation of macromolecular systems at physiologically relevant timescales. Herein, we discuss the impact of diverse structure-based and ligand-based molecular modeling techniques in d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190304123545
更新日期:2019-01-01 00:00:00
abstract::Human serum albumin (HSA) is one of the major carrier proteins in the body and constitutes approximately half of the protein found in blood plasma. It plays an important role in lipid metabolism, and its ability to reversibly bind a large variety of pharmaceutical compounds makes it a crucial determinant of drug pharm...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150304163447
更新日期:2015-01-01 00:00:00
abstract::Rapid increase in the emergence and spread of microbes resistant to conventionally used antibiotics has become a major threat to global health care. Antimicrobial peptides (AMPs) are considered as a potential source of novel antibiotics because of their numerous advantages such as broad-spectrum activity, lower tenden...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990003
更新日期:2013-01-01 00:00:00
abstract::The diatomic molecule of oxygen contains two uncoupled electrons and can therefore undergo reduction, yielding several different oxygen metabolites, which are collectively called Reactive Oxygen Species or ROS. They are invariably produced in aerobic environments through a variety of mechanisms, which include electron...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384664
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Coronavirus Disease-2019 belongs to the family of viruses which cause a serious pneumonia along with fever, breathing issues and infection of lungs for the first time in China and later spread worldwide. OBJECTIVE:Several studies and clinical trials have been conducted to identify potential drugs and vaccin...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201118103416
更新日期:2020-11-17 00:00:00
abstract::Inhaled glucocorticoids, also know as corticosteroids (ICS), revolutionized the treatment of asthma by suppressing airways inflammation and ICS therapy now forms the basis of treatment of asthma of all severities. More recently and usually in combination with a long-acting β-agonist (LABA), ICS use has been establishe...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161210793797889
更新日期:2010-01-01 00:00:00
abstract::Depression is one of the leading causes of disability in the world. Current pharmaceutical treatment for depression remains unsatisfactory due to its limited therapeutic efficacy and undesirable side effects. There is increasing interest in looking for alternative strategies from diet for the treatment of depressive d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180803113106
更新日期:2018-01-01 00:00:00
abstract::The antimicrobial agents used in the treatment of mycobacterial infections have remained largely unchanged for several decades. Primary treatment of tuberculosis relies on four drugs, isoniazid, a rifamycin, pyrazinamide, and ethambutol (or streptomycin), and generally results in >95% cure in uncomplicated tuberculosi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043383296
更新日期:2004-01-01 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::Fibrate derivatives have a 40-year history in the management of dyslipidemia. Although this class of drugs is generally well tolerated, several safety issues have arisen from their use. In the present article we review the literature describing side effects associated with the use of fibrates except for those that are...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208783885362
更新日期:2008-01-01 00:00:00
abstract::The prevalence of type 2 diabetes is rising at an alarming rate worldwide. Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the diabetic population. Future CAD risk should be routinely assessed in patients with diabetes as specific subgroups might benefit from information derived from c...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786071272
更新日期:2008-01-01 00:00:00
abstract::Obesity, a chronic low-grade inflammation disorder characterized by an expansion in adipose tissue mass, is rapidly expanding worldwide leading to an increase in the incidence of comorbidities such as insulin resistance, type 2 diabetes and cardiovascular diseases. This has led to a renewed interest in the adipose tis...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151109111958
更新日期:2016-01-01 00:00:00
abstract::Reverse transcriptase (RT) is one of the most important targets for HIV drug discovery. However, the emergence of resistant mutants has become one of the biggest challenges in HIV-1 RT drug discovery/development and attracted great research interests worldwide. It is particularly important to develop novel anti-HIV-1 ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161282005140214163439
更新日期:2014-01-01 00:00:00