p53 Throws CRISPR a Curve.

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：: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：:The enzyme methylenetetrahydrofolate reductase (MTHFR) directs folate species either to DNA synthesis or to homocysteine (Hcy) remethylation. The common MTHFR C677T polymorphism affects the activity of the enzyme and hence folate distribution. Under conditions of impaired folate status, the homozygous TT genotype has ...

journal_title：Trends in pharmacological sciences

authors： Ueland PM,Hustad S,Schneede J,Refsum H,Vollset SE

更新日期：2001-04-01 00:00:00

abstract：:Lithium is the simplest therapeutic agent available for the treatment of depression and has been used for over 100 years, yet no definitive mechanism for its effect has been established. Among the proposed mechanisms, two lithium-sensitive signal transduction pathways are active in the brain; these are mediated by gly...

journal_title：Trends in pharmacological sciences

authors： Williams RS,Harwood AJ

更新日期：2000-02-01 00:00:00

abstract：:The vascular system is rich in G-protein-coupled receptors (GPCRs), particularly Class 1 GPCRs, which are activated by an eclectic range of chemical entities including peptides. These chemical messengers can function in blood vessels as directly acting vasoconstrictors, directly acting vasodilators or indirectly actin...

journal_title：Trends in pharmacological sciences

authors： Maguire JJ,Davenport AP

更新日期：2005-09-01 00:00:00

abstract：:The broad importance of receptor-activated phosphoinositide hydrolysis in the physiological action of hormones, neurotransmitters and growth factors has sparked interest in the study of transmembrane signalling events responsible for activation of phospholipase C. As with receptors involved in regulation of adenylyl c...

journal_title：Trends in pharmacological sciences

authors： Boyer JL,Hepler JR,Harden TK

更新日期：1989-09-01 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

authors： van Herwaarden AE,van Waterschoot RA,Schinkel AH

更新日期：2009-05-01 00:00:00

abstract：:Recruitment of leukocytes either during development or to the site of injury is crucial. The molecular regulation of cell trafficking is complex but well orchestrated by the temporal and spatial expression of a multitude of chemokines (chemoattractant cytokines) and chemokine receptors. The chemokines, classified prim...

journal_title：Trends in pharmacological sciences

authors： Devalaraja MN,Richmond A

更新日期：1999-04-01 00:00:00

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

authors： Bayry J,Kaveri SV

更新日期：2018-11-01 00:00:00

abstract：:Recent advances in schizophrenia (SZ) research indicate that the telencephalic gamma-aminobutyric acid (GABA)ergic neurotransmission deficit associated with this psychiatric disorder probably is mediated by the hypermethylation of the glutamic acid decarboxylase 67 (GAD(67)), reelin and other GABAergic promoters. A ph...

journal_title：Trends in pharmacological sciences

authors： Guidotti A,Dong E,Kundakovic M,Satta R,Grayson DR,Costa E

更新日期：2009-02-01 00:00:00

abstract：:Bioluminescence resonance energy transfer has developed in recent years as a new technique to study protein-protein interactions. Protein partners of interest are tagged with either luciferase or green fluorescent protein (GFP). Non-radiative energy transfer between the excited luciferase and the GFP permits the study...

journal_title：Trends in pharmacological sciences

authors： Boute N,Jockers R,Issad T

更新日期：2002-08-01 00:00:00

abstract：:Until recently, release studies have failed to indicate the existence of autoreceptors on motor nerves. Ignaz Wessler now reports on a refinement of the technique - the measurement of newly synthesized [3H]acetylcholine released from the phrenic nerve - which provides clear evidence in support of release-modulating au...

journal_title：Trends in pharmacological sciences

authors： Wessler I

更新日期：1989-03-01 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：: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：: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

abstract：:This year marks the 90th anniversary of the publication of Hans Horst Meyer's classic paper in which he proposed that the ability of a substance to produce narcosis or anesthesia is governed by its partition coefficient. In this article, Robert Lipnick describes the experiments carried out by Meyer and his colleagues ...

journal_title：Trends in pharmacological sciences

authors： Lipnick RL

更新日期：1989-07-01 00:00:00

abstract：:Data sets from recent large-scale projects can be integrated into one unified puzzle that can provide new insights into how drugs and genetic perturbations applied to human cells are linked to whole-organism phenotypes. Data that report how drugs affect the phenotype of human cell lines and how drugs induce changes in...

journal_title：Trends in pharmacological sciences

authors： Ma'ayan A,Rouillard AD,Clark NR,Wang Z,Duan Q,Kou Y

更新日期：2014-09-01 00:00:00

abstract：:Endothelial-dependent relaxation of vascular smooth muscle cells evoked by a number of agonists, including cholinomimetics and substance P, is often accompanied by an increase (repolarization and/or hyperpolarization) in the membrane potential. This change in membrane potential appears predominantly to reflect the act...

journal_title：Trends in pharmacological sciences

authors： Garland CJ,Plane F,Kemp BK,Cocks TM

更新日期：1995-01-01 00:00:00

abstract：:The injectisome type three secretion system (T3SS) is a major virulence factor in Pseudomonas aeruginosa. This bacterium is responsible for severe infections in immunosuppressed or cystic fibrosis patients and has become resistant to many antibiotics. Inhibitors of T3SS may therefore constitute an innovative therapeut...

journal_title：Trends in pharmacological sciences

authors： Anantharajah A,Mingeot-Leclercq MP,Van Bambeke F

更新日期：2016-09-01 00:00:00

abstract：:Muscarinic agonists open potassium-selective K(ACh) channels in cardiac myocytes of pacemaker or atrial origin. Receptor activation is coupled to channel opening by a membrane bound guanine nucleotide-binding protein (GK) through a process that does not require cytoplasmic intermediates. We have used the muscarinic po...

journal_title：Trends in pharmacological sciences

authors： Szabo G,Otero AS

更新日期：1989-12-01 00:00:00

abstract：:N-Methyl-D-aspartate (NMDA) receptors are tetrameric ion channels containing two of four possible GluN2 subunits. These receptors have been implicated for decades in neurological diseases such as stroke, traumatic brain injury, dementia and schizophrenia. The GluN2 subunits substantially contribute to functional diver...

journal_title：Trends in pharmacological sciences

authors： Ogden KK,Traynelis SF

更新日期：2011-12-01 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：:It has been hypothesized that anxiety disorders play an important role in the initiation and maintenance of alcohol drinking behaviors. However, the molecular mechanisms for the association between anxiety and alcohol abuse are not well understood. Structures of the extended amygdala, particularly the central nucleus ...

journal_title：Trends in pharmacological sciences

authors： Pandey SC

更新日期：2003-09-01 00:00:00

abstract：:The physiological roles of chemokine receptors have expanded beyond host defense and now represent important targets for intervention in several disease indications. Chemokine receptors have joined the ranks of other members of the G-protein-coupled receptor (GPCR) family in therapeutic potential as small-molecule che...

journal_title：Trends in pharmacological sciences

authors： Onuffer JJ,Horuk R

更新日期：2002-10-01 00:00:00

abstract：:The pursuit for drugs that inhibit cyclin-dependent kinases (CDKs) has been an intense area of research for more than 15 years. The first-generation inhibitors, Flavopiridol and CY-202, are in late-stage clinical trials, but so far have demonstrated only modest activity. Several second-generation inhibitors are now in...

journal_title：Trends in pharmacological sciences

authors： Malumbres M,Pevarello P,Barbacid M,Bischoff JR

更新日期：2008-01-01 00:00:00

abstract：:Central nervous system (CNS) drug development has been plagued by a failure to translate effective therapies from the lab to the clinic. There are many potential reasons for this, including poor understanding of brain pharmacokinetic (PK) and pharmacodynamic (PD) factors, preclinical study flaws, clinical trial design...

journal_title：Trends in pharmacological sciences

authors： Dragunow M

更新日期：2020-11-01 00:00:00

abstract：:Histamine-containing neurons and histamine H1 receptors are distributed within the brain and peripheral tissues. The results of physiological and pharmacological studies have revealed that brain histamine and H1 receptors are involved in the regulation of feeding and obesity in rodents. The adipocytokine leptin regula...

journal_title：Trends in pharmacological sciences

authors： Masaki T,Yoshimatsu H

更新日期：2006-05-01 00:00:00

abstract：:Elucidating plant-specialized biosynthetic pathways has always constituted a laborious task, notably for natural products with high pharmaceutical values. Here, we discuss emerging omics-based strategies that facilitate the identification of genes from these complex metabolic pathways, paving the way to engineered sup...

journal_title：Trends in pharmacological sciences

authors： Dugé de Bernonville T,Papon N,Clastre M,O'Connor SE,Courdavault V

更新日期：2020-03-01 00:00:00

abstract：:Behavioural pharmacology is an interdisciplinary field at the intersection of several research areas that ultimately lead to the development of drugs for clinical use and build understanding of how brain functions enable cognition and behaviour. In this article, the development of behavioural pharmacology in the UK is...

journal_title：Trends in pharmacological sciences

authors： Robbins TW,Murphy ER

更新日期：2006-03-01 00:00:00

abstract：:Intercellular transfer of proteins is a mode of communication between cells that is crucial for certain physiological processes. Chemotherapy is the treatment of choice for approximately 50% of all cancers. However, multidrug resistance mediated by drug-efflux pumps such as P-glycoprotein (Pgp) minimizes the effective...

journal_title：Trends in pharmacological sciences

authors： Ambudkar SV,Sauna ZE,Gottesman MM,Szakacs G

更新日期：2005-08-01 00:00:00