p53 Throws CRISPR a Curve.


:The efficacy of the powerful CRISPR-Cas9 genome-editing platform depends on DNA repair activities in the cells being targeted. Two new papers show that the low efficiency of targeting in some primary human cell lines is the result of p53-dependent cell arrest in response to the Cas9-induced break. This limitation must be overcome for some anticipated therapies.


Trends Pharmacol Sci


Carroll D




Has Abstract


2018-09-01 00:00:00














  • Frizzleds as GPCRs - More Conventional Than We Thought!

    abstract::For more than 30 years, WNT/β-catenin and planar cell polarity signaling has formed the basis for what we understand to be the primary output of the interaction between WNTs and their cognate receptors known as Frizzleds (FZDs). In the shadow of these pathways, evidence for the involvement of heterotrimeric G proteins...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Schulte G,Wright SC

    更新日期:2018-09-01 00:00:00

  • Eosinophil lysis and free granules: an in vivo paradigm for cell activation and drug development.

    abstract::Release of cytotoxic granule proteins from activated eosinophil granules is considered to be a key pathogenic mechanism in eosinophilic diseases. Degenerated eosinophils and extracellular eosinophil granules have been repeatedly depicted. The present overview describes evidence that eosinophil lysis and distribution o...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Persson CG,Erjefält JS

    更新日期:1997-04-01 00:00:00

  • Inflammation and neurodegeneration: the story 'retolled'.

    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


    authors: Drouin-Ouellet J,Cicchetti F

    更新日期:2012-10-01 00:00:00

  • Biological responses towards cationic peptides and drug carriers.

    abstract::In drug development, major resources are invested into the development of cellular delivery systems to increase the effectiveness of a large array of potential therapeutics, such as proteins and oligonucleotides. These carriers comprise cell-penetrating peptides (CPPs), cationic lipids and cationic polymers. In recent...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Verdurmen WP,Brock R

    更新日期:2011-02-01 00:00:00

  • Toxicology of simple and complex mixtures.

    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

    pub_type: 杂志文章,评审


    authors: Groten JP,Feron VJ,Sühnel J

    更新日期:2001-06-01 00:00:00

  • Preclinical models of antipsychotic drug-induced metabolic side effects.

    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


    authors: Boyda HN,Tse L,Procyshyn RM,Honer WG,Barr AM

    更新日期:2010-10-01 00:00:00

  • The pathophysiology and pharmacology of hepcidin.

    abstract::Inappropriate production of the iron-regulatory hormone hepcidin contributes to the pathogenesis of common iron disorders. Absolute or relative deficiency of hepcidin causes iron overload in hereditary hemochromatosis and iron-loading anemias. Elevated hepcidin causes iron restriction in inflammatory conditions includ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Ruchala P,Nemeth E

    更新日期:2014-03-01 00:00:00

  • GPCRs in NLRP3 Inflammasome Activation, Regulation, and Therapeutics.

    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


    authors: Tang T,Gong T,Jiang W,Zhou R

    更新日期:2018-09-01 00:00:00

  • Three-finger snake neurotoxins and Ly6 proteins targeting nicotinic acetylcholine receptors: pharmacological tools and endogenous modulators.

    abstract::Snake venom neurotoxins and lymphocyte antigen 6 (Ly6) proteins, most of the latter being membrane tethered by a glycosylphosphatidylinositol (GPI) anchor, have a variety of biological activities, but their three-finger (3F) folding combines them in one Ly6/neurotoxin family. Subsets of two groups, represented by α-ne...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Tsetlin VI

    更新日期:2015-02-01 00:00:00

  • Adenosine A2B receptors: a novel therapeutic target in asthma?

    abstract::Adenosine is an endogenous nucleoside that modulates many physiological processes. Its actions are mediated by interaction with specific cell membrane receptors. Four subtypes of adenosine receptor have been cloned: A1, A2A, A2B and A3. Significant advancement has been made in our understanding of the molecular pharma...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Feoktistov I,Polosa R,Holgate ST,Biaggioni I

    更新日期:1998-04-01 00:00:00

  • Balancing prostanoid activity in the human vascular system.

    abstract::The imbalance theory proposes that arterial thrombosis is dependent on a ratio or balance between the cyclooxygenase (COX)-1-dependent generation of thromboxane in platelets and the COX-2-dependent generation of prostacyclin in the endothelium. Accordingly, by reducing endothelium-derived prostacyclin levels, selectiv...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Flavahan NA

    更新日期:2007-03-01 00:00:00

  • The 'ABC' of GABA receptors.

    abstract::In the conventional view, GABA acts at either ionotropic GABAA or metabotropic GABAB receptors. Recently, novel ionotropic GABA receptors that are composed of rho-subunits have been identified in the vertebrate retina. These bicuculline- and baclofen-insensitive GABA receptors are frequently called GABAC, following an...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Bormann J

    更新日期:2000-01-01 00:00:00

  • Small molecule SIRT1 activators for the treatment of aging and age-related diseases.

    abstract::Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, potentially extending healthy years of life. In this review, we discuss recent advances, controversies, opportunities, and ch...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Hubbard BP,Sinclair DA

    更新日期:2014-03-01 00:00:00

  • The annexin 1 receptor(s): is the plot unravelling?

    abstract::Recent studies have proposed a functional link between annexin 1 (ANXA1), an endogenous anti-inflammatory mediator, and receptors of the formyl-peptide family. In particular, exogenous and endogenous ANXA1 and its peptidomimetics interact with one member of this family, the formyl-peptide-receptor-like 1. Further anal...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Perretti M

    更新日期:2003-11-01 00:00:00

  • NADPH oxidases: novel therapeutic targets for neurodegenerative diseases.

    abstract::Oxidative stress is a key pathologic factor in neurodegenerative diseases such as Alzheimer and Parkinson diseases (AD, PD). The failure of free-radical-scavenging antioxidants in clinical trials pinpoints an urgent need to identify and to block major sources of oxidative stress in neurodegenerative diseases. As a maj...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Gao HM,Zhou H,Hong JS

    更新日期:2012-06-01 00:00:00

  • Endothelium-dependent hyperpolarization: a role in the control of vascular tone.

    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

    pub_type: 杂志文章,评审


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

    更新日期:1995-01-01 00:00:00

  • Lean Big Data integration in systems biology and systems pharmacology.

    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

    pub_type: 杂志文章


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

    更新日期:2014-09-01 00:00:00

  • Computational Approaches to Anesthetic Drug Discovery.

    abstract::All currently available general anesthetics produce potentially deadly side effects. Unfortunately, few approaches have been developed to design safer ones, despite important advances in anesthetic mechanisms research. Cayla and colleagues recently showed that computational methods can be used to identify anesthetic l...

    journal_title:Trends in pharmacological sciences

    pub_type: 评论,杂志文章


    authors: McGrath M,Pence A,Raines DE

    更新日期:2019-11-01 00:00:00

  • Targeting PAR1: Now What?

    abstract::Protease-activated receptors (PARs) are a ubiquitously expressed class of G-protein-coupled receptors (GPCRs) that enable cells to respond to proteases in the extracellular environment in a nuanced and dynamic manner. PAR1 is the archetypal family member and has been the object of large-scale drug development programs...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Flaumenhaft R,De Ceunynck K

    更新日期:2017-08-01 00:00:00

  • Targets in ALS: designing multidrug therapies.

    abstract::Amyotrophic lateral sclerosis (ALS) is an incurable disease that arises from the progressive loss of motoneurons. Even when caused by a single gene defect, as in the case of mutations in the enzyme Cu-Zn superoxide dismutase (SOD1), ALS is the result of a complex cascade that involves crosstalk among motoneurons, glia...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Carrì MT,Grignaschi G,Bendotti C

    更新日期:2006-05-01 00:00:00

  • Pleiotropic functions of biliverdin reductase: cellular signaling and generation of cytoprotective and cytotoxic bilirubin.

    abstract::Degradation of heme requires its conversion to biliverdin (BV) by heme oxygenase, followed by reduction of BV to the free-radical quencher bilirubin (BR) by biliverdin reductase (BVR). It is now recognized that human BVR (hBVR) is a dual-specificity kinase (Ser/Thr and Tyr) upstream activator of the insulin/insulin gr...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Kapitulnik J,Maines MD

    更新日期:2009-03-01 00:00:00

  • GABA and its receptors in the spinal cord.

    abstract::The importance of the inhibitory neurotransmitter, GABA, within higher centres of the mammalian brain is unquestionable. However, its role within the spinal cord is of equal significance. There have been numerous studies over the past two decades that have established GABA as a neurotransmitter at both post- and presy...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Malcangio M,Bowery NG

    更新日期:1996-12-01 00:00:00

  • GPCR deorphanizations: the novel, the known and the unexpected transmitters.

    abstract::Pairing orphan G-protein-coupled receptors (GPCRs) to potential ligands found in tissue extracts or in libraries of synthetic compounds has identified an ever-increasing number of transmitters, some of which are novel, some of which were previously known and, more recently, some of which are unexpected. These discover...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Civelli O

    更新日期:2005-01-01 00:00:00

  • Neoceptors: reengineering GPCRs to recognize tailored ligands.

    abstract::Efforts to model and reengineer the putative binding sites of G-protein-coupled receptors (GPCRs) have led to an approach that combines small-molecule 'classical' medicinal chemistry and gene therapy. In this approach, complementary structural changes (e.g. based on novel ionic or H-bonds) are made in the receptor and...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Jacobson KA,Gao ZG,Liang BT

    更新日期:2007-03-01 00:00:00

  • Regulation of the expression and function of the M2 muscarinic receptor.

    abstract::Since the cloning and expression of many of the G protein-coupled receptors during the 1980s, there has been a massive increase in our understanding of many aspects of their function. The use of molecular biology to engineer and express mutant receptors has made it possible to determine key amino acids involved in rec...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Haddad el-B,Rousell J

    更新日期:1998-08-01 00:00:00

  • Similarities between the Yin/Yang Doctrine and Hormesis in Toxicology and Pharmacology.

    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

    pub_type: 杂志文章,评审


    authors: Sun H,Calabrese EJ,Lin Z,Lian B,Zhang X

    更新日期:2020-08-01 00:00:00

  • Discoidin Domains as Emerging Therapeutic Targets.

    abstract::Discoidin (DS) domains are found in eukaryotic and prokaryotic extracellular and transmembrane multidomain proteins. These small domains play different functional roles and can interact with phospholipids, glycans, and proteins, including collagens. DS domain-containing proteins are often involved in cellular adhesion...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Villoutreix BO,Miteva MA

    更新日期:2016-08-01 00:00:00

  • Siglecs as targets for therapy in immune-cell-mediated disease.

    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


    authors: O'Reilly MK,Paulson JC

    更新日期:2009-05-01 00:00:00

  • Size matters in activation/inhibition of ligand-gated ion channels.

    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

    pub_type: 杂志文章,评审


    authors: Du J,Dong H,Zhou HX

    更新日期:2012-09-01 00:00:00

  • Intracellular 5-HT 2C-receptor dephosphorylation: a new target for treating drug addiction.

    abstract::The 5-hydroxytryptamine (5-HT)(2C) receptor has received considerable attention as a target for treating drug addiction. 5-HT(2C)-receptor agonism, however, also induces side-effects. In this article, we review recent findings regarding the involvement of 5-HT(2C) receptors in behaviours related to drug addiction in a...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Müller CP,Carey RJ

    更新日期:2006-09-01 00:00:00