Abstract：
:Tumor necrosis factor (TNF, TNF-α, cachectin) is a pleiotropic, proinflammatory cytokine with multiple biological effects, many of which are not yet fully understood. Although TNF was initially described as an anti-tumor agent more than three decades ago, current knowledge places it central to immune system homeostasis. TNF plays a critical role in host defense against infection, as well as an inhibitory role in autoimmune disease. However, TNF overproduction generates deleterious effects by inducing the transcription of genes involved in acute and chronic inflammatory responses including asthma, rheumatoid arthritis, Crohn's disease, and psoriasis. Direct inhibition of TNF by biologics, such as monoclonal antibodies and circulating TNF receptor constructs, has produced effective treatments for these disorders and validated the inhibition of this proinflammatory cytokine as an effective therapy. Unfortunately, these biological therapies suffer from several drawbacks, including high cost and the induction of autoantibody production. Thus, the development of small molecules able to modulate TNF production or signaling pathways remains a central challenge in Medicinal Chemistry. Considerable efforts have been made over the past two decades to develop such inhibitors, which could potentially be administered orally and would presumably be cheaper. This review is focused on the recent development of compounds that modulate the activity of this cytokine by acting at different levels, such as TNF expression, processing, binding to its receptors and direct inhibition. These approaches will be compared and discussed.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Richmond V,Michelini FM,Bueno CA,Alché LE,Ramírez JAdoi
10.2174/0929867322666150729115553subject
Has Abstractpub_date
2015-01-01 00:00:00pages
2920-42issue
25eissn
0929-8673issn
1875-533Xpii
CMC-EPUB-69152journal_volume
22pub_type
杂志文章,评审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
更新日期：2016-01-01 00:00:00
abstract：:Vitamin D has been known for a long time as a major factor involved in the calcium- phosphate balance and homeostasis, along with parathyroid hormone (PTH). While vitamin D effects on calcium and phosphate are fully known, recent studies attempted to link vitamin D status and cardiovascular diseases. The involvement o...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/0929867323666160405112019
更新日期：2016-01-01 00:00:00
abstract：:Cardiovascular pathologies in the French are not prevalent despite high dietary saturated fat consumption. This is commonly referred to as the "French Paradox" attributing its anti-lipidemic effects to moderate consumption of red wine. Resveratrol, a phytoalexin found in red wine, is currently the focus of intense res...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/092986708784638861
更新日期：2008-01-01 00:00:00
abstract：:In their structural multiplicity and in the extent to which they occur in nature the derivatives of benzofuran are significantly lesser than the isoelectronic analogue indoles. However, these heterocyclic compounds show a variety of pharmacological properties, and change of their structure offers a high degree of dive...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/092986709787002826
更新日期：2009-01-01 00:00:00
abstract：:Thalidomide (N-alpha-phthalimidoglutarimide) was used widely as a hypnotic/sedative agent in the late 1950s and the early 1960s, but had to be withdrawn from the market because of its severe teratogenicity. In spite of this, there has been a resurgence of interest in the drug in recent years due to its potential usefu...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：
更新日期：1998-06-01 00:00:00
abstract：: ...
journal_title：Current medicinal chemistry
pub_type： 社论
doi：10.2174/092986732533181024105316
更新日期：2018-01-01 00:00:00
abstract：BACKGROUND:Antimicrobial resistance is found in all microorganisms and has become one of the biggest threats to global health. New antimicrobials with different action mechanisms are effective weapons to fight against antibiotic-resistance. OBJECTIVE:This review aims to find potential drugs which can be further develo...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/0929867324666171106160326
更新日期：2019-01-01 00:00:00
abstract：:Transglutaminases (TGases) are enzymes which catalyze the cross linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate with the formation of an N-gamma-(epsilon-L-glutamyl)-L-lysine [GGEL] cross link (isopeptidic bond) and the concomitant release of ammonia....
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/092986706777585068
更新日期：2006-01-01 00:00:00
abstract：:The oxime formation reaction of therapeutical progestogen (levonorgestrel, levonorgestrel acetate, norethisterone), androgen (methyltestosterone, testosterone phenylpropionate) and anabolic (nortestosterone phenylpropionate) Delta(4)-3-ketosteroids has been investigated. The ketosteroid-hydroxylamine reaction was moni...
journal_title：Current medicinal chemistry
pub_type： 杂志文章
doi：10.2174/0929867013372238
更新日期：2001-09-01 00:00:00
abstract：:Alzheimer's disease (AD) is a highly complex and rapidly progressive neurodegenerative disorder characterized by the systemic collapse of cognitive function and formation of dense amyloid plaques and neurofibrillary tangles. AD pathology is derived from the cholinergic, amyloid and tau hypotheses, respectively. Curren...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/092986711797200435
更新日期：2011-01-01 00:00:00
abstract：:Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), the rate-limiting enzyme of cholesterol synthesis. In recent years, statins have become the major choice of treatment for hypercholesterolemia. Emerging evidence from both animal and human studies indicates that mechanisms i...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/0929867033457205
更新日期：2003-08-01 00:00:00
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
更新日期：2006-01-01 00:00:00
abstract：:Rubus species (family Rosaceae) have been cultivated for centuries for their fruits. These and other parts of the plants have been used traditionally for therapeutic purposes. This article highlights these and the potential they can offer. The constituents reported in the various species and those demonstrated to exhi...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/0929867043365143
更新日期：2004-06-01 00:00:00
abstract：:Neural differentiation of embryonic stem cells (ESC) is considered a promising model to perform in vitro testing for neuroactive and neurotoxic compounds. We studied the potential of a dual reporter murine ESC line to identify bioactive and/or toxic compounds. This line expressed firefly luciferase under the control o...
journal_title：Current medicinal chemistry
pub_type： 杂志文章
doi：10.2174/092986713804999330
更新日期：2013-01-01 00:00:00
abstract：:The focus of this review is the cellular internalisation mechanism of nanostructured systems (NSs) and their endosomal escape for targeted drug delivery. Endocytosis is a cellular process of internalisation of different molecules and foreign microorganisms. It is currently being studied for drug delivery through nanos...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/0929867324666170214111205
更新日期：2017-01-01 00:00:00
abstract：:Bile formation is an osmotic process driven by the vectorial transport of actively transferred biliary components across the basolateral (sinusoidal) and apical (canalicular) hepatocyte membranes, the latter being the rate-limiting step of the overall blood-to-bile transfer. The ATP-binding cassette (ABC) superfamily ...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/0929867043455918
更新日期：2004-02-01 00:00:00
abstract：:Analytical chemists have increasingly turned their attention to drug discovery and drug analysis and to solve fundamental questions of biological significance in physiology and genetics. New technologies have been developed, and a variety of instruments have been redesigned for biomedical applications. The development...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/0929867310504050501
更新日期：2005-01-01 00:00:00
abstract：:The term Lewy body diseases (LBDs) refers to a subset of neurodegenerative disorders that share the accumulation of the so-called Lewy bodies (LB) including: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and PD later characterized by the occurrence of dementia (PDD). Moreover, multiple system atrophy (MSA...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/0929867324666170609080000
更新日期：2018-01-01 00:00:00
abstract：:Obesity and metabolic syndrome represent major public health problems, and are the biggest preventable causes of death worldwide. Obesity is the leading risk factor for type 2 diabetes mellitus (T2DM), cardiovascular diseases and non-alcoholic fatty liver disease. Obesity-associated insulin resistance, which is charac...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/0929867311320210001
更新日期：2013-01-01 00:00:00
abstract：:Trypanosomatids are a group of flagellated unicellular eukaryotes, causing serious human diseases including Chagas disease (Trypanosoma cruzi), sleeping sickness (Trypanosoma brucei spp.) and Leishmaniasis (Leishmania spp.). The second messenger cAMP is involved in numerous and fundamental processes in these parasites...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/0929867326666190620093029
更新日期：2019-01-01 00:00:00
abstract：:Inosine monophosphate dehydrogenase (IMPDH) catalyzes the conversion of IMP to XMP with the concomitant reduction of NAD to NADH. This reaction is the rate-limiting step in guanine nucleotide biosynthesis. IMPDH is a proven target for immunosuppressive, anticancer and antiviral chemotherapy, and may also be a target f...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：
更新日期：1999-07-01 00:00:00
abstract：:Dimerization and oligomerization of G protein-coupled receptors (GPCRs), proposed almost 30 years ago, have crucial relevance for drug design. Indeed, formation of GPCR oligomers may affect the diversity and performance by which extracellular signals are transferred to G proteins in the process of receptor transductio...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/092986711797379285
更新日期：2011-01-01 00:00:00
abstract：:Matrix metalloproteinase-9 (MMP-9) plays an important role in the onset and prognosis of myocardial infarction. Targets of angiotensin converting enzyme (ACE) inhibitors might include not only ACE but also MMP-9, and ACE seems to be closely associated with complications of hypertension such as cardiovascular remodelin...
journal_title：Current medicinal chemistry
pub_type： 杂志文章
doi：10.2174/092986709787846514
更新日期：2009-01-01 00:00:00
abstract：:Neonatal brain hemorrhage (NBH) of prematurity is an unfortunate consequence of preterm birth. Complications result in shunt dependence and long-term structural changes such as posthemorrhagic hydrocephalus, periventricular leukomalacia, gliosis, and neurological dysfunction. Several animal models are available to stu...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/0929867322666150114152421
更新日期：2015-01-01 00:00:00
abstract：:Diabetic patients have a two- to four-fold increased risk for the development of microvascular (renal, neuronal and retinal) and macrovascular complications. Unfortunately, these complications may develop in both Type 1 and Type 2 diabetic patients even with careful glycaemic, blood pressure and lipid control. With th...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/092986706777452515
更新日期：2006-01-01 00:00:00
abstract：:Balance between excitatory glutamate and inhibitory GABA neurotransmitter is essential and critical for proper development and functioning of brain. GABAergic (gamma aminobutyric acid) and glutamatergic interneurons maintain excitability, integrity and synaptic plasticity. Several evidences implicated relative loss of...
journal_title：Current medicinal chemistry
pub_type： 杂志文章
doi：10.2174/0929867322666150209152712
更新日期：2015-05-04 00:00:00
abstract：:Molecules in biological systems often can perform more than one function. In particular, many molecules have the ability to chemically scavenge free radicals and thus act in the test tube as antioxidant, but their main biological function is by acting as hormones, ligands for transcription factors, modulators of enzym...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/0929867043365332
更新日期：2004-05-01 00:00:00
abstract：:The reductive conversion of ribonucleotides to deoxyribonucleotides by ribonucleotide reductase (RR) is a crucial and rate-controlling step in the pathway leading to the biosynthesis of DNA, since deoxyribonucleotides are present in extremely low levels in mammalian cells. Mammalian ribonucleotide reductase (RR) is co...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/0929867013373741
更新日期：2001-02-01 00:00:00
abstract：:Synthetic compounds with a tri- and tetra-substituted imidazole scaffold are known as selective inhibitors of the p38 mitogen-activated protein (MAP) kinase responsible for proinflammatory cytokine release. The scope is to review the literature describing their design, synthesis and activity studies. To date a great p...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/092986711795328409
更新日期：2011-01-01 00:00:00
abstract：:Fungal phytotoxins are natural secondary metabolites produced by plant pathogenic fungi during host-pathogen interactions. They have received considerable particular attention for elucidating disease etiology, and consequently to design strategies for disease control. Due to wide differences in their chemical structur...
journal_title：Current medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/0929867324666170426152331
更新日期：2018-01-01 00:00:00
