Off-target effects associated with long dsRNAs in Drosophila RNAi screens.

abstract：:Drug development consumes huge amounts of time and money and the search for novel analgesics, which are urgently required, is particularly difficult, having resulted in many setbacks in the past. Drug repurposing - the identification of new uses for existing drugs - is an alternative approach, which bypasses most of t...

journal_title：Trends in pharmacological sciences

authors： Sisignano M,Parnham MJ,Geisslinger G

更新日期：2016-03-01 00:00:00

abstract：:NMDA and non-NMDA (AMPA/kainate) antagonists have potential in the treatment of a diverse group of neurological disorders associated with excessive activation of excitatory amino acid receptors. Here Michael Rogawski reviews recent progress in the development of therapeutically useful NMDA receptor channel blockers an...

journal_title：Trends in pharmacological sciences

authors： Rogawski MA

更新日期：1993-09-01 00:00:00

abstract：:Chronic obstructive pulmonary disease (COPD) is caused mostly by cigarette smoking but its specific molecular mechanisms are obscure. Current theories suggest that the inflammation and oxidative stress induced by smoking lead to proteolytic imbalance and progressive lung structural derangement, with disease susceptibi...

journal_title：Trends in pharmacological sciences

authors： Anderson GP,Bozinovski S

更新日期：2003-02-01 00:00:00

abstract：:There is increasing awareness of the compartmentalization of cAMP signalling--the means by which cAMP levels change in discrete domains of the cell with discrete local consequences. Current developments in understanding the organization of adenylyl cyclases in the plasma membrane are illuminating how the earliest part...

journal_title：Trends in pharmacological sciences

authors： Cooper DM,Crossthwaite AJ

更新日期：2006-08-01 00:00:00

abstract：:Pharmacologists have studied receptors for more than a century but a molecular understanding of their properties has emerged only during the past 30-35 years. In this article, I provide a personal retrospective of how developments and discoveries primarily during the 1970s and 1980s led to current concepts about the l...

journal_title：Trends in pharmacological sciences

authors： Lefkowitz RJ

更新日期：2004-08-01 00:00:00

abstract：:Five subtypes of muscarinic acetylcholine receptors have been identified in mammalian tissues, but the selectivity of ligands that are active at these receptors is low. It is possible, however, that selective compounds may be developed by targeting their allosteric site(s). Important new insights into the mechanism of...

journal_title：Trends in pharmacological sciences

authors： Tucek S,Proska J

更新日期：1995-06-01 00:00:00

abstract：:The concept that receptors can exist in multiple conformational states is becoming a physical reality. A fundamental question is how many active states need to be proposed in order to account for pharmacological observations, in particular, the finding that the same receptor type can exhibit a different agonist pharma...

journal_title：Trends in pharmacological sciences

authors： Leff P,Scaramellini C,Law C,McKechnie K

更新日期：1997-10-01 00:00:00

abstract：:B7x (B7 homolog x, also known as B7-H4, B7S1, and VTCN1) was discovered by ourselves and others in 2003 as the seventh member of the B7 family. It is an inhibitory immune checkpoint of great significance to human disease. Tissue-expressed B7x minimizes autoimmune and inflammatory responses. It is overexpressed in a br...

journal_title：Trends in pharmacological sciences

authors： John P,Wei Y,Liu W,Du M,Guan F,Zang X

更新日期：2019-11-01 00:00:00

abstract：:The breast cancer resistance protein [BCRP (also known as ABCG2)] belongs to the ATP binding cassette (ABC) family of transmembrane drug transporters. BCRP has a broad substrate specificity and actively extrudes a wide variety of drugs, carcinogens and dietary toxins from cells. Situated in the apical plasma membrane ...

journal_title：Trends in pharmacological sciences

authors： van Herwaarden AE,Schinkel AH

更新日期：2006-01-01 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

authors： Schapira AH

更新日期：2009-01-01 00:00:00

abstract：:Carbonic anhydrase isoform IX (CA IX) is highly overexpressed in many types of cancer. Its expression, which is regulated by the HIF-1 transcription factor, is strongly induced by hypoxia and correlates with a poor response to classical chemo- and radiotherapies. CA IX contributes to acidification of the tumor environ...

journal_title：Trends in pharmacological sciences

authors： Thiry A,Dogné JM,Masereel B,Supuran CT

更新日期：2006-11-01 00:00:00

abstract：:The rise of multidrug-resistant pathogens and the dearth of new antibiotic development place an existential strain on successful infectious disease therapy. Breakthrough strategies that go beyond classical antibiotic mechanisms are needed to combat this looming public health catastrophe. Reconceptualizing antibiotic t...

journal_title：Trends in pharmacological sciences

authors： Munguia J,Nizet V

更新日期：2017-05-01 00:00:00

abstract：:Adenosine, when given by inhalation, initiates the narrowing of airways in subjects with asthma or chronic obstructive pulmonary disease (COPD). The underlying mechanism of this narrowing appears to involve the stimulation of specific mast cell surface adenosine receptors with the subsequent release of mediators and c...

journal_title：Trends in pharmacological sciences

authors： Spicuzza L,Bonfiglio C,Polosa R

更新日期：2003-08-01 00:00:00

abstract：:Influenza A viral infections claim millions of lives worldwide and continue to impose a major burden on healthcare systems. Current pharmacological strategies to control influenza A virus-induced lung disease are problematic owing to antiviral resistance and the requirement for strain-specific vaccination. The product...

journal_title：Trends in pharmacological sciences

authors： Vlahos R,Stambas J,Selemidis S

更新日期：2012-01-01 00:00:00

abstract：:G protein-coupled receptors (GPCRs) comprise a large and diverse class of signal-transducing receptors that undergo dynamic and isoform-specific membrane trafficking. GPCRs thus have an inherent potential to initiate or regulate signaling reactions from multiple membrane locations. This review discusses emerging insig...

journal_title：Trends in pharmacological sciences

authors： Eichel K,von Zastrow M

更新日期：2018-02-01 00:00:00

abstract：:Humans are exposed to mixtures of chemicals, rather than to individual chemicals. From a public health point of view, it is most relevant to answer the question of whether or not the components in a mixture interact in a way that results in an increase in their overall effect compared with the sum of the effects of th...

journal_title：Trends in pharmacological sciences

authors： Groten JP,Feron VJ,Sühnel J

更新日期：2001-06-01 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

authors： Maccarrone M,Bab I,Bíró T,Cabral GA,Dey SK,Di Marzo V,Konje JC,Kunos G,Mechoulam R,Pacher P,Sharkey KA,Zimmer A

更新日期：2015-05-01 00:00:00

abstract：:Pharmacology training in Canada was initiated at McGill University in Montréal in 1824, and there are now 17 pharmacology departments in Canada offering graduate training to more than 500 students. In this article, Gerald Marks reviews the growth of pharmacology in Canada since the early 19th century in both academic ...

journal_title：Trends in pharmacological sciences

authors： Marks GS

更新日期：1994-07-01 00:00:00

abstract：:For almost 70 years, children have received stimulants for the treatment of attention deficit hyperactivity disorder [ADHD (initially called hyperkinetic syndrome)], with little understanding of the long-term effects of these drugs on brain development. The maturation and refinement of the brain during childhood and a...

journal_title：Trends in pharmacological sciences

authors： Andersen SL

更新日期：2005-05-01 00:00:00

abstract：:cGMP inhibits hypertrophy, decreases fibrosis, and protects against cardiac ischemia-reperfusion (I/R) injury. Gene-targeting studies have not defined a clear role for its major downstream effector, cGMP-dependent protein kinase I (cGKI), in cardiac hypertrophy, but do implicate cGMP-cGKI signaling in fibrosis and I/R...

journal_title：Trends in pharmacological sciences

authors： Lukowski R,Krieg T,Rybalkin SD,Beavo J,Hofmann F

更新日期：2014-08-01 00:00:00

abstract：:Cys loop, glutamate, and P2X receptors are ligand-gated ion channels (LGICs) with 5, 4, and 3 protomers, respectively. There is now growing atomic level understanding of their gating mechanisms. Although each family is unique in the architecture of the ligand-binding pocket, the pathway for motions to propagate from l...

journal_title：Trends in pharmacological sciences

authors： Du J,Dong H,Zhou HX

更新日期：2012-09-01 00:00:00

abstract：:Nearly all molecules known to signal cells via G proteins have been assigned a cloned G-protein-coupled-receptor (GPCR) gene. This has been the result of a decade-long genetic search that has also identified some receptors for which ligands are unknown; these receptors are described as orphans (oGPCRs). More than 80 o...

journal_title：Trends in pharmacological sciences

authors： Marchese A,George SR,Kolakowski LF Jr,Lynch KR,O'Dowd BF

更新日期：1999-09-01 00:00:00

abstract：:During the past decade, translocator protein 18 kDa (TSPO), previously named peripheral benzodiazepine receptor, has gained a great deal of attention based on its use as a clinical biomarker of neuroinflammation with therapeutic potential. However, there is a paucity of knowledge on the function(s) of TSPO in glial ce...

journal_title：Trends in pharmacological sciences

authors： Guilarte TR,Loth MK,Guariglia SR

更新日期：2016-05-01 00:00:00

abstract：:Three 'alpha 1-adrenoceptors' and three 'alpha 2-adrenoceptors' have now been cloned. How closely do these receptors match the native receptors that have been identified pharmacologically? What are the properties of these receptors, and how do they relate to other members of the cationic amine receptor family? Kevin L...

journal_title：Trends in pharmacological sciences

authors： Harrison JK,Pearson WR,Lynch KR

更新日期：1991-02-01 00:00:00

abstract：:Plants have been the predominant source of medicines throughout the vast majority of human history, and remain so today outside of industrialized societies. One of the most versatile in terms of its phytochemistry is cannabis, whose investigation has led directly to the discovery of a unique and widespread homeostatic...

journal_title：Trends in pharmacological sciences

authors： Russo EB

更新日期：2016-07-01 00:00:00

abstract：:Transcription factors comprise just over 7% of the human proteome and serve as gatekeepers of cellular function, integrating external signal information into gene expression programs that reconfigure cellular physiology at the most basic levels. Surface-initiated cell signaling pathways converge on transcription facto...

journal_title：Trends in pharmacological sciences

authors： Filtz TM,Vogel WK,Leid M

更新日期：2014-02-01 00:00:00

abstract：:Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in developed nations. Therapeutic modulation of dyslipidemia by inhibiting 3'-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is standard practice throughout the world. However, based on findings from Mendelian ...

journal_title：Trends in pharmacological sciences

authors： Sathiyakumar V,Kapoor K,Jones SR,Banach M,Martin SS,Toth PP

更新日期：2018-08-01 00:00:00

abstract：:Docking is now routine in virtual screening or lead optimization for drug screening and design. The number of papers related to docking has dramatically increased over the past decade. However, there are many issues to consider when undertaking a docking study. Frequent problems or issues arise, such as the wrong bind...

journal_title：Trends in pharmacological sciences

authors： Chen YC

更新日期：2015-02-01 00:00:00

abstract：:Network and systems biology offer a novel way of approaching drug discovery by developing models that consider the global physiological environment of protein targets, and the effects of modifying them, without losing the key molecular details. Here we review some recent advances in network and systems biology applied...

journal_title：Trends in pharmacological sciences

authors： Pujol A,Mosca R,Farrés J,Aloy P

更新日期：2010-03-01 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

authors： Kenakin T

更新日期：2007-08-01 00:00:00