Discoidin Domains as Emerging Therapeutic Targets.


: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, migration, proliferation, and matrix-remodeling events, while some play a major role in blood coagulation. Mutations in DS domains have been associated with various disease conditions. This review provides an update on the structure, function, and modulation of the DS domains, with a special emphasis on two circulating blood coagulation cofactors, factor V and factor VIII, and the transmembrane neuropilin receptors that have been targeted for inhibition by biologics and small chemical compounds.


Trends Pharmacol Sci


Villoutreix BO,Miteva MA




Has Abstract


2016-08-01 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

  • P2 purinoceptors on vascular endothelial cells: physiological significance and transduction mechanisms.

    abstract::The characterization of P2 gamma purinoceptors on vascular endothelial cells has progressed rapidly since their existence was first demonstrated in 1983. They transduce the actions of extracellular ATP and ADP--endothelium-dependent relaxation, prostacyclin synthesis, endothelial cell mitogenesis--which play a vital r...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Boeynaems JM,Pearson JD

    更新日期:1990-01-01 00:00:00

  • Computational studies to predict or explain G protein coupled receptor polypharmacology.

    abstract::Since G protein-coupled receptors (GPCRs) belong to a very large superfamily of evolutionarily related receptors (>800 members in humans), and due to the rapid progress on their structural biology, they are ideal candidates for polypharmacology studies. Broad screening and bioinformatics/chemoinformatics have been app...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章


    authors: Jacobson KA,Costanzi S,Paoletta S

    更新日期:2014-12-01 00:00:00

  • Cancer and Microenvironment Plasticity: Double-Edged Swords in Metastasis.

    abstract::Cancer initiates at one site (primary tumor) and, in most cases, spreads to other distant organs (metastasis). During the multistep process of metastasis, primary tumor cells acquire cellular and phenotypic plasticity to survive and thrive in different environments. Moreover, cancer cells also utilize and educate micr...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Zhuang X,Zhang H,Hu G

    更新日期:2019-06-01 00:00:00

  • Feedback Activation of STAT3 as a Cancer Drug-Resistance Mechanism.

    abstract::Signal transducer and activator of transcription 3 (STAT3) plays crucial roles in several cellular processes such as cell proliferation and survival, and has been found to be aberrantly activated in many cancers. Much research has explored the leading mechanisms for regulating the STAT3 pathway and its role in promoti...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Zhao C,Li H,Lin HJ,Yang S,Lin J,Liang G

    更新日期:2016-01-01 00:00:00

  • Phospholipase A2 enzymes: regulation and inhibition.

    abstract::The phospholipase A2 enzymes are important components of the cellular machinery that responds to inflammatory stimuli and maintains cell homeostasis by membrane remodelling. Their role as the rate-limiting step in the production of pro-inflammatory lipid mediators makes these enzymes an important therapeutic target fo...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Glaser KB,Mobilio D,Chang JY,Senko N

    更新日期:1993-03-01 00:00:00

  • Newly discovered tachykinins raise new questions about their peripheral roles and the tachykinin nomenclature.

    abstract::The tachykinin family has recently been extended by the discovery of a third tachykinin gene encoding previously unknown mammalian tachykinins (hemokinin 1, endokinin A and endokinin B) that have a widespread peripheral distribution and a tachykinin NK(1) receptor selectivity. This and the identification of other tach...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Patacchini R,Lecci A,Holzer P,Maggi CA

    更新日期:2004-01-01 00:00:00

  • Exploring the potential of adjunct therapy in tuberculosis.

    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


    authors: Rayasam GV,Balganesh TS

    更新日期:2015-08-01 00:00:00

  • RGS9-2: probing an intracellular modulator of behavior as a drug target.

    abstract::Regulators of G-protein signaling (RGS proteins) comprise a large family of signal transduction molecules that modulate G-protein-coupled-receptor (GPCR) function. Among the RGS proteins expressed in the brain, RGS9-2 is very abundant in the striatum, a brain region involved in movement, motivation, mood and addiction...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章


    authors: Traynor JR,Terzi D,Caldarone BJ,Zachariou V

    更新日期:2009-03-01 00:00:00

  • Excitatory actions of adenosine on ventricular automaticity.

    abstract::Due to its negative chronotropic and inotropic effects, adenosine has to date been considered as a cardiodepressant agent. However, adenosine increases ventricular automaticity. This review by Jesus Hernández and Alexandre Ribeiro discusses the experimental and clinical evidence for the excitatory effects of adenosine...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Hernández J,Ribeiro JA

    更新日期:1996-04-01 00:00:00

  • Subcellular Organization of GPCR Signaling.

    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

    pub_type: 杂志文章,评审


    authors: Eichel K,von Zastrow M

    更新日期:2018-02-01 00:00:00

  • Rho kinase: a target for treating urinary bladder dysfunction?

    abstract::Urinary incontinence and other urinary storage symptoms are frequent in the general population but available treatments have limited efficacy and tolerability. Rho kinase (ROCK) has a central role in the regulation of smooth muscle contraction, including that of the urinary bladder. Recent experimental evidence indica...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Peters SL,Schmidt M,Michel MC

    更新日期:2006-09-01 00:00:00

  • An Emerging Circuit Pharmacology of GABAA Receptors.

    abstract::In the past 20 years we have learned a great deal about GABAA receptor (GABAAR) subtypes, and which behaviors are regulated or which drug effects are mediated by each subtype. However, the question of where GABAARs involved in specific drug effects and behaviors are located in the brain remains largely unanswered. We ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Engin E,Benham RS,Rudolph U

    更新日期:2018-08-01 00:00:00

  • The benzodiazepine binding site of GABAA receptors.

    abstract::The GABAA receptor belongs, along with the nicotinic acetylcholine receptor, the glycine receptor and the 5-HT3 receptor, to a family of homologous transmitter-gated ion channels mediating fast synaptic transmission. Many classes of drug interact with the GABAA receptor, which is the major inhibitory ion channel in th...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Sigel E,Buhr A

    更新日期:1997-11-01 00:00:00

  • Identifying Missing Biosynthesis Enzymes of Plant Natural Products.

    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

    pub_type: 杂志文章


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

    更新日期:2020-03-01 00:00:00

  • The sweet taste of true synergy: positive allosteric modulation of the human sweet taste receptor.

    abstract::A diet low in carbohydrates helps to reduce the amount of ingested calories and to maintain a healthy weight. With this in mind, food and beverage companies have reformulated a large number of their products, replacing sugar or high fructose corn syrup with several different types of zero-calorie sweeteners to decreas...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章


    authors: Servant G,Tachdjian C,Li X,Karanewsky DS

    更新日期:2011-11-01 00:00:00

  • Protein kinase Calpha: disease regulator and therapeutic target.

    abstract::Protein kinase Calpha (PKCalpha) is a member of the AGC (which includes PKD, PKG and PKC) family of serine/threonine protein kinases that is widely expressed in mammalian tissues. It is closely related in structure, function and regulation to other members of the protein kinase C family, but has specific functions wit...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Konopatskaya O,Poole AW

    更新日期:2010-01-01 00:00:00

  • Does the pharmacology of oxycodone justify its increasing use as an analgesic?

    abstract::Oxycodone is a semisynthetic opioid analgesic that is increasingly used for the treatment of acute, cancer, and chronic non-malignant pain. Oxycodone was synthesized in 1917 but its pharmacological properties were not thoroughly studied until recently. Oxycodone is a fairly selective μ-opioid receptor agonist, but the...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Olkkola KT,Kontinen VK,Saari TI,Kalso EA

    更新日期:2013-04-01 00:00:00

  • Biological and clinical implications of the MTHFR C677T polymorphism.

    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

    pub_type: 杂志文章,评审


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

    更新日期:2001-04-01 00:00:00

  • Kill 'Em All: Efgartigimod Immunotherapy for Autoimmune Diseases.

    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


    authors: Bayry J,Kaveri SV

    更新日期:2018-11-01 00:00:00

  • Suppressing production of reactive oxygen species (ROS) for influenza A virus therapy.

    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

    pub_type: 杂志文章,评审


    authors: Vlahos R,Stambas J,Selemidis S

    更新日期:2012-01-01 00:00:00

  • Characterization of the action of antipsychotic subtypes on valproate-induced chromatin remodeling.

    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

    pub_type: 杂志文章


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

    更新日期:2009-02-01 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

  • Diverse functions of muscarinic acetylcholine receptor subtypes.

    abstract::Muscarinic acetylcholine receptor subtypes m1, m3 and m5 couple strongly to phosphatidylinositol turnover and hence to intracellular Ca2+ concentration via pertussis toxin (PTX) sensitive and insensitive G proteins. The m2 and m4 muscarinic receptor subtypes strongly inhibit adenylyl cyclase production via PTX sensiti...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Lechleiter J,Peralta E,Clapham D

    更新日期:1989-12-01 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

  • Novel Therapeutic Targets for Managing Dyslipidemia.

    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

    pub_type: 杂志文章,评审


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

    更新日期:2018-08-01 00:00:00

  • New insights into activation of the steroid hormone receptor superfamily.

    abstract::For many years the prevailing view of how steroid hormone receptors exert their effects on gene transcription has been that these intracellular receptor proteins, upon association with their specific cognate ligands, undergo a transformation to a state where they are capable of interacting with chromatin and regulatin...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Power RF,Conneely OM,O'Malley BW

    更新日期:1992-08-01 00:00:00

  • Pilot the pulse: controlling the multiplicity of receptor dynamics.

    abstract::G protein-coupled receptors (GPCRs) are involved in almost every (patho)physiological process, which explains their importance as drug targets. GPCRs have long been regarded as on/off-switches, which is reflected by direct activation or blockade of these receptors through the majority of marketed GPCR drugs. In recent...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章


    authors: Bock A,Kostenis E,Tränkle C,Lohse MJ,Mohr K

    更新日期:2014-12-01 00:00:00

  • Protein engineering and the study of structure--function relationships in receptors.

    abstract::Protein engineering is a powerful tool for studying relationships between receptor structure and function--providing that it is used and interpreted appropriately. Site-directed mutagenesis, deletion mutagenesis and construction of chimaeric proteins have all been used to characterize receptors. In this review, Walter...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章,评审


    authors: Ward WH,Timms D,Fersht AR

    更新日期:1990-07-01 00:00:00

  • Phosphodiesterases reduce spontaneous sinoatrial beating but not the 'fight or flight' tachycardia elicited by agonists through Gs-protein-coupled receptors.

    abstract::Cyclic AMP (cAMP) steers the generation of basal heart beat in the sinoatrial node. It also induces sinoatrial tachycardia and increased cardiac force, elicited through activation of Gs-protein-coupled receptors (GsPCRs). Phosphodiesterases (PDEs) hydrolyse cAMP. In the heart mainly PDE3 and PDE4 would be expected to ...

    journal_title:Trends in pharmacological sciences

    pub_type: 杂志文章


    authors: Kaumann AJ

    更新日期:2011-07-01 00:00:00