Abstract:
:The therapeutic advantage of reducing the activity of interleukin 1 (IL-1) resides in preventing its deleterious biological effects without interfering with homeostasis. As such, methods attempting to block the production or activity of IL-1 have now entered clinical trials. For example, IL-1 induction of prostaglandins is one target in treating disease, and drugs preventing the production of inhibiting cyclooxygenase have well-known toxicities because they block the normal synthesis of prostaglandins in many tissues. IL-1 blockading agents, in contrast, affect only that portion of prostaglandin synthesis due to elevated IL-1, sparing the synthesis of these molecules for homeostasis. Charles Dinarello reviews the unique pharmacological advantages of manipulating IL-1.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Dinarello CAdoi
10.1016/0165-6147(93)90200-4subject
Has Abstractpub_date
1993-05-01 00:00:00pages
155-9issue
5eissn
0165-6147issn
1873-3735pii
0165-6147(93)90200-4journal_volume
14pub_type
杂志文章,评审abstract::A critical unmet need for treatment of drug-resistant tuberculosis (TB) is to find novel therapies that are efficacious, safe, and shorten the duration of treatment. Drug discovery approaches for TB primarily target essential genes of the pathogen Mycobacterium tuberculosis (Mtb) but novel strategies such as host-dire...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2015.05.005
更新日期:2015-08-01 00:00:00
abstract::14-3-3 Proteins enact a range of cellular functions through protein-protein interactions (PPIs) with client proteins. Kaplan and colleagues recently demonstrated that a semisynthetic compound was able to selectively stabilize or disrupt specific interactions, depending on the binding partner. This finding presents an ...
journal_title:Trends in pharmacological sciences
pub_type: 评论,杂志文章
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abstract::K(+) channels are macromolecules embedded in biological membranes, where they play a key role in cellular excitability and signal transduction pathways. Knowledge of their structure should help improve our understanding of their function and lead to the design of therapeutic compounds. Most pharmacological and structu...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/S0165-6147(03)00080-4
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abstract::The vascular endothelium is a remarkably heterogeneous organ. In addition to well-characterized anatomical diversity in situ, specific differences are increasingly being recognized between surface antigens on endothelial cells from different tissues, including absence of the classic endothelial marker factor VIII-rela...
journal_title:Trends in pharmacological sciences
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doi:10.1016/0165-6147(91)90637-8
更新日期:1991-12-01 00:00:00
abstract::In 1964, the psychoactive ingredient of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC), was isolated. Nearly 30 years later the endogenous counterparts of THC, collectively termed endocannabinoids (eCBs), were discovered: N-arachidonoylethanolamine (anandamide) (AEA) in 1992 and 2-arachidonoylglycerol (2-AG) in 1995...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2015.02.008
更新日期:2015-05-01 00:00:00
abstract::From the deep part of the main ligand-binding crevice, a minor, often shallower pocket extends between the extracellular ends of transmembrane domains (TM)-I, II, III and VII of 7TM receptors. This minor binding pocket is defined by a highly conserved kink in TM-II that is induced by a proline residue located in one o...
journal_title:Trends in pharmacological sciences
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abstract::Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing conserved motifs predominantly found in microorganisms. Increasing evidence supports a role for TLRs in sterile inflammation as observed in neurodegenerative disorders. This includes work suggesting a contribution for these receptors to t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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abstract::The use of genetically-engineered mice has identified alpha2- and alpha3-subunit containing GABA(A) receptors as principal contributors to the spinal disinhibition that occurs after inflammation and neuropathic injury. Pharmacological comparison of subtype selective allosteric modulators such as NS11394 and L838417 wi...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2009.06.004
更新日期:2009-09-01 00:00:00
abstract::It has been suggested that G protein-coupled receptors can act as proton transporters, with the activated G protein-coupled receptor transporting H+ across the membrane from the extracellular side to the cytoplasm. In this article, Paul Nederkoorn, Henk Timmerman and Gabriëlle Donné-Op den Kelder summarize the various...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(00)89008-2
更新日期:1995-05-01 00:00:00
abstract::It has been over 50years since Sir James Black developed the first beta adrenergic receptor (βAR) blocker to treat heart disease. At that time, the concept of cell surface receptors was relatively new and not widely accepted, and most of the tools currently used to characterize plasma membrane receptors had not been d...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2011.02.005
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abstract::Neonatal Fc receptors (FcRns) recycle IgGs by preventing their lysosome degradation. As this process also enhances half-life of pathogenic auto-IgG, inspired from the mechanisms of intravenous immunoglobulin, several inhibitors of IgG-FcRn interface have been conceived for treating autoimmune diseases. Among them, the...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2018.08.004
更新日期:2018-11-01 00:00:00
abstract::Daily rhythms in behavior, physiology, and metabolism are an integral part of homeostasis. These rhythms emerge from interactions between endogenous circadian clocks and ambient light-dark cycles, sleep-activity cycles, and eating-fasting cycles. Nearly the entire primate genome shows daily rhythms in expression in ti...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2018.07.003
更新日期:2018-09-01 00:00:00
abstract::Ca2+ channels in the plasma membrane of T cells vitally influence Ca2+-dependent signals that lead ultimately to cytokine secretion, cellular proliferation and apoptosis. Conventional models depict the Ca2+ inrush across the T-cell membrane following T-cell receptor engagement as being due to Ca2+-release-activated Ca...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2006.05.007
更新日期:2006-07-01 00:00:00
abstract::Hormesis is a generalizable dose-response relationship characterized by low-dose stimulation and high-dose inhibition. Despite debate over this biphasic dose-response curve, hormesis is challenging central beliefs in the evaluation of chemicals or drugs and has influenced biological model selection, concentration rang...
journal_title:Trends in pharmacological sciences
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更新日期:2020-08-01 00:00:00
abstract::Antipsychotic drugs (APDs), and the 'atypical' APDs in particular, are commonly associated with metabolic side effects in humans. These include glucose dysregulation, insulin resistance, hyperlipidemia, weight gain and hypertension, which put patients at increased risk of cardiometabolic disorders. The underlying biol...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2010.07.002
更新日期:2010-10-01 00:00:00
abstract::Controversy over the meaning of pharmacological parameters often arises because of a lack of appreciation of different hierarchical levels of analysis. In a recent letter in Trends in Pharmacological Sciences, Zhang and Kavana [1] concluded that my two-state model for allosterism lacks cooperativity, even though Figur...
journal_title:Trends in pharmacological sciences
pub_type: 评论,信件
doi:10.1016/j.tips.2016.06.001
更新日期:2016-08-01 00:00:00
abstract::The NLRP3 inflammasome is an intracellular multimeric protein complex which plays an important role in the pathogenesis of various human inflammatory diseases, such as diabetes, Alzheimer's disease and atherosclerosis. Recently, various G protein-coupled receptors (GPCRs) have been reported to be involved in the activ...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2018.07.002
更新日期:2018-09-01 00:00:00
abstract::Molecular forms of acetylcholinesterase exhibit tissue-specific distribution, and each form is anchored to the cell surface via a particular post-translational modification of the catalytic subunit. Nibaldo Inestrosa and Alejandra Perelman review evidence that heparan sulphate proteoglycans are the extracellular matri...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/0165-6147(89)90067-9
更新日期:1989-08-01 00:00:00
abstract::Seven-transmembrane receptors are prototypic allosteric proteins with the ability to adopt numerous conformations, many of which interact with cellular partners to initiate cellular biochemical processes. Defining efficacy as the ability of ligands to stabilize some of these conformations (which, in turn, possess phys...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2007.06.009
更新日期:2007-08-01 00:00:00
abstract::Traditional African medicine (TAM) is a shorthand reference to indigenous forms of healing that are practiced all over Africa. Although TAM is based on the accumulated experience of ancient Africans, its mode of transmission by word-of-mouth has hindered emergence of a generally accepted theory and hence of the system...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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更新日期:1999-12-01 00:00:00
abstract::Clinical implementation of two recently approved antisense RNA therapeutics - Exondys51® to treat Duchenne muscular dystrophy (Duchenne MD) and Spinraza® as a treatment for spinal muscular atrophy (SMA) - highlights the therapeutic potential of antisense oligonucleotides (ASOs). As shown in the Duchenne and Becker cas...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2018.09.001
更新日期:2018-11-01 00:00:00
abstract::It is generally accepted that seven-transmembrane receptors have the capacity to regulate cellular signaling systems in the absence of occupancy by a ligand (i.e. the receptors display constitutive activity). Drugs can increase (agonists), decrease (inverse agonists) or not change (antagonists) receptor activity towar...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2005.10.008
更新日期:2005-12-01 00:00:00
abstract::The genotoxicity of the most potent carcinogen in cigarette smoke [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)] is dependent on the relationship between its activation by cytochrome P450 enzymes and its detoxification by carbonyl reduction to NNK alcohol (NNAL) followed by glucuronidation. Recently, '11 beta-...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/s0165-6147(97)01090-0
更新日期:1997-08-01 00:00:00
abstract::Cytochrome P450 3A (CYP3A) enzymes metabolize a wide variety of xenobiotics including many drugs. Because CYP3A is localized in both the liver and intestine, it can make a major contribution to the presystemic elimination of substrate drugs after oral administration ('first-pass metabolism'). However, assessments of t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章
doi:10.1016/j.tips.2009.02.003
更新日期:2009-05-01 00:00:00
abstract::Successful biologics must satisfy multiple properties including activity and particular physicochemical features that are globally defined as developability. These multiple properties must be simultaneously optimized in a very broad design space of protein sequences and buffer compositions. In this context, artificial...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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更新日期:2021-01-23 00:00:00
abstract::Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease and is an important cause of chronic disability. Numerous important advances have been made in our understanding of the aetiopathogenesis, pathology and clinical phenomenology of this disease, and these have underpi...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2008.10.005
更新日期:2009-01-01 00:00:00
abstract::The sialic-acid-binding immunoglobulin-like lectins (siglecs) comprise a family of receptors that are differentially expressed on leukocytes and other immune cells. The restricted expression of several siglecs to one or a few cell types makes them attractive targets for cell-directed therapies. The anti-CD33 (also kno...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
doi:10.1016/j.tips.2009.02.005
更新日期:2009-05-01 00:00:00
abstract::Current medicines for the clinical management of inflammatory diseases act by inhibiting specific enzymes or antagonising specific receptors or blocking their ligands. In the past decade, a new paradigm in our understanding of the inflammatory process has emerged with the appreciation of genetic, molecular, and cellul...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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更新日期:2015-11-01 00:00:00
abstract::As we have learnt from earlier articles in our series on the pharmacology of excitatory amino acids, neurons and glia express several subtypes of excitatory amino acid receptor, the activation of which increases intracellular free calcium ion concentration. In this sixth article, Mark Mayer and Richard Miller detail t...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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更新日期:1990-06-01 00:00:00
abstract::The potent pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin 1 (IL-1) are capable of triggering biologically similar effects through activation of the same set of transcription factors. Based on recent findings it is now becoming evident that certain members of the mitogen-activated p...
journal_title:Trends in pharmacological sciences
pub_type: 杂志文章,评审
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更新日期:1997-09-01 00:00:00