Abstract:
:Aberrant expression of chemokines and their receptors play causative roles in the pathophysiology of numerous autoimmune and inflammatory disease processes. Moreover, an integral step in HIV infection involves binding to chemokine receptors, and hence chemokines are intimately linked to HIV-related diseases. Therefore, chemokines and their receptors are excellent targets for developing drugs that are more specific and may be of benefit in the management of disease. Knowledge of the chemokine and chemokine receptor structures, and an understanding of the structural basis of their function are essential for structure-aided design of receptor decoys. Chemokine ligands bind their receptors with nanomolar (nM) affinity, and successful design of a small molecule antagonist should bind the receptor with similar high affinity and specificity. Chemokines bind receptors that belong to the 7-transmembrane class on leukocytes, and highly negatively charged proteoglycans that are present on the cell surface. Structure-function studies have identified regions in both the ligand and the receptor that mediate binding and activation. Structures of numerous chemokines have been solved though very little is known regarding receptor structures. This review will summarize the current knowledge on the structures, structure-function, and the efficacy of chemokine derivatives and functional domain peptides as antagonists, and discuss strategies for exploiting this information for designing decoys for inflammatory, autoimmune, and HIV-related diseases.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Rajarathnam Kdoi
10.2174/1381612023393233subject
Has Abstractpub_date
2002-01-01 00:00:00pages
2159-69issue
24eissn
1381-6128issn
1873-4286journal_volume
8pub_type
杂志文章,评审abstract::Senescence is defined as an irreversible growth arrest that is characterised by a changed morphology, gene expression pattern and chromatin structure as well as an activated DNA damage response. Senescence has a dual role for tumour development-it acts as a tumour suppressor to prevent the proliferation of seriously d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210789941874
更新日期:2010-01-01 00:00:00
abstract::Oxidative processes exert a fundamental regulatory function during pregnancy. It depends on the influence of oxygen, nitric oxide, reactive oxygen species and reactive nitrogen species metabolic pathways upon the vascular changes in the maternal organism, as well as on the regulation of uterine and cervical tone throu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054065747
更新日期:2005-01-01 00:00:00
abstract::Cardiovascular diseases remain the leading cause of morbidity and mortality among postmenopausal women in western societies. There are still no specific and highly efficient methods of preservation of women's vascular health in modern preventive medicine. For many years physicians have assumed that hormone replacement...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151112150520
更新日期:2016-01-01 00:00:00
abstract::Somatostatin is a tetradeca peptide hormone produced by many different endocrine cells throughout the body. It is also present in both the central and peripheral nervous system. The peptide has many different moods of action including inhibition of hormone secretion and influence on gastrointestinal motility. Somatost...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:1999-09-01 00:00:00
abstract::The essential nature of rapid radiotracer synthesis very early in drug discovery programs has driven the need for better and more varied tritium incorporation methods. This review presents a summary of recent advances for tritium introduction via tritiated water, tritium gas, complex tritides, and a range of recently ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003399969
更新日期:2000-07-01 00:00:00
abstract::The involvement of the central nervous system (CNS) is one of the major causes of morbidity and mortality in systemic lupus erythematosus (SLE) patients and the less understood aspect of the disease. Its recognition and treatment continue to represent a major diagnostic and therapeutic challenge. Due to the lack of co...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208799316401
更新日期:2008-01-01 00:00:00
abstract::Reducing sugars can react non-enzymatically with amino groups of proteins and lipids to form irreversibly cross-linked macroprotein derivatives called as advanced glycation end products (AGEs). Cross-linking modification of extracellular matrix proteins by AGEs deteriorate their tertiary structural integrity and funct...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161021155502
更新日期:2017-01-01 00:00:00
abstract::Asthma is an allergic disease that affects approximately 300 million people worldwide. Two of its phenotypes routinely assessed at the clinic include airway hyperresponsiveness and IgE production. They can be measured in a non-invasive manner and have been used for genetic studies. The genetic complexity of asthma and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160829141708
更新日期:2016-01-01 00:00:00
abstract::Thrombotic events occurring in either arteries or veins are the primary causes of fatal perioperative cardiovascular events. Risk factors for deep vein thrombosis, several of which are evidently associated with specific surgical procedures, are quite different from those for arterial thrombosis (e.g., aging or atheros...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140204102044
更新日期:2014-01-01 00:00:00
abstract::Inflammatory Bowel Diseases (IBD) are now widely receiving attention. There are many reasons why people get IBD; for example, environment, smoking, family heredity, intestinal microbiota and so on. Antibiotics have not been proven effective and those suffering from IBD have begun to look for other effective drugs to t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180829103945
更新日期:2018-01-01 00:00:00
abstract::Psychoneuroimmunology is a relatively young field of research that investigates interactions between central nervous and immune system. The brain modulates the immune system by the endocrine and autonomic nervous system. Vice versa, the immune system modulates brain activity including sleep and body temperature. Based...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212802502305
更新日期:2012-01-01 00:00:00
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::Pulmonary arterial hypertension (PAH) is a severe vascular complication of connective tissue diseases. In the context of systemic sclerosis (SSc), PAH is a devastating disease with a dramatic impact on prognosis and survival. Despite advances in early diagnosis and the development of new targeted treatments, SSc-relat...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212799504704
更新日期:2012-01-01 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::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::This review is based on carriers of natural origin such as polysaccharides, proteins, and cell derived entities which have been used for delivery of siRNA. To realize the therapeutic potential of a delivery system, the role of the carrier is of utmost importance. Historical aspects of viral vectors, the first carriers...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161282131151013185528
更新日期:2015-01-01 00:00:00
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 ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113196660743
更新日期:2014-01-01 00:00:00
abstract::Curcumin is a natural polyphenol product derived from the rhizome of the Curcuma longa. In vivo and in vitro studies have uncovered many important bioactivities of curcumin, such as antioxidant activity, inducing cell apoptosis, inhibiting cell proliferation, anti-cell adhesion and motility, anti-angiogenesis and anti...
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::Metal ions that leach into biotherapeutic drug product solution during manufacturing and storage, result in contamination that can cause physico-chemical degradation of the active molecule. In this review, we describe various mechanisms by which metal ion leachates can interact with therapeutic proteins and antibodies...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990063
更新日期:2014-01-01 00:00:00
abstract::Macrophages are professional scavengers of apoptotic and necrotic cells, and hence constantly take up self antigens. Paradoxically, macrophages are also professional antigen-presenting cells, which would seem to invite autoimmune disorders. Moreover, macrophages are effector cells in the tissue-destruction phase of au...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033392026
更新日期:2003-01-01 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::Hypericin is a naturally occurring substance found in the common St. John's Wort (Hypericum species) and can also be synthesized from the anthraquinone derivative emodin. As the main component of Hypericum perforatum, it has traditionally been used throughout the history of folk medicine. In the last three decades, hy...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053382287
更新日期:2005-01-01 00:00:00
abstract::The liver acts as a host to many functions hence raising the possibility that any one may be compromised by a single gene defect. Inherited or de novo mutations in these genes may result in relatively mild diseases or be so devastating that death within the first weeks or months of life is inevitable. Some diseases ca...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211797247541
更新日期:2011-01-01 00:00:00
abstract::Topiramate is one of the currently most promising compounds in the field of addiction medicine. This paper discusses its potential utility related to a phase model of addiction development, focusing on the assumption that addiction is a continuous process involving different neurobiological pathways, depending on the ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161211796150864
更新日期:2011-01-01 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 signal transducer and activator of transcription 3 (STAT3) transduces stress signals from the plasma membrane to the nucleus but has recently also been identified in mitochondria. Inhibition of cardiomyocyte mitochondrial STAT3 with the STAT3-specific inhibitor Stattic decreases ADP-stimulated respiration and enha...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161281939131127115940
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Polycystic ovary syndrome (PCOS) is a frequent female reproductive endocrine disease. It has been associated with a number of severe reproductive and metabolic abnormalities. However, there are still open questions especially regarding the best long-term management. METHODS:We summarized the literature focu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190130104922
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is a global epidemic involving 20-40% of the general population. NAFLD is rapidly becoming the leading cause of hepatocellular carcinoma (HCC) worldwide. Knowledge about NAFLD-HCC peculiar features is needed to understand this emerging disease better. OBJECTIVE:To r...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200429093648
更新日期:2020-01-01 00:00:00
abstract::The review describes key aspects of the synthesis and biological activities of conjugates of oligonucleotides and their analogues with synthetic peptides, in particular aimed towards gene silencing applications. The common methods of synthesis of oligonucleotide-peptide conjugates (OPCs) and PNA-peptide conjugates (PP...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161205774580769
更新日期:2005-01-01 00:00:00
abstract::The development of targeted therapy drugs acting on tumor growth and progression is greatly expanding these last years. Among them kinase inhibitors have a prominent position and have demonstrated efficacy and clinical benefits in solid and hematologic malignancies. Compared to conventional systemic cytotoxic chemothe...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160226132630
更新日期:2016-01-01 00:00:00