当前位置： SCI文献检索 > MOLECULAR PHARMACOLOGY期刊下所有文献 > High-throughput screening reveals a small-molecule inhibitor of the renal outer medullary potassium channel and Kir7.1.

High-throughput screening reveals a small-molecule inhibitor of the renal outer medullary potassium channel and Kir7.1.

Abstract：

:The renal outer medullary potassium channel (ROMK) is expressed in the kidney tubule and critically regulates sodium and potassium balance. The physiological functions of other inward rectifying K(+) (Kir) channels expressed in the nephron, such as Kir7.1, are less well understood in part due to the lack of selective pharmacological probes targeting inward rectifiers. In an effort to identify Kir channel probes, we performed a fluorescence-based, high-throughput screen (HTS) of 126,009 small molecules for modulators of ROMK function. Several antagonists were identified in the screen. One compound, termed VU590, inhibits ROMK with submicromolar affinity, but has no effect on Kir2.1 or Kir4.1. Low micromolar concentrations inhibit Kir7.1, making VU590 the first small-molecule inhibitor of Kir7.1. Structure-activity relationships of VU590 were defined using small-scale parallel synthesis. Electrophysiological analysis indicates that VU590 is an intracellular pore blocker. VU590 and other compounds identified by HTS will be instrumental in defining Kir channel structure, physiology, and therapeutic potential.

journal_name

Mol Pharmacol

journal_title

Molecular pharmacology

authors

Lewis LM,Bhave G,Chauder BA,Banerjee S,Lornsen KA,Redha R,Fallen K,Lindsley CW,Weaver CD,Denton JS

doi

10.1124/mol.109.059840

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

1094-103

issue

5

eissn

0026-895X

issn

1521-0111

pii

mol.109.059840

journal_volume

76

pub_type

杂志文章

相关文献

MOLECULAR PHARMACOLOGY文献大全
  • Soluble guanylyl cyclase activator YC-1 protects white matter axons from nitric oxide toxicity and metabolic stress, probably through Na(+) channel inhibition.

    abstract：:In the rat isolated optic nerve, nitric oxide (NO) activates soluble guanylyl cyclase (sGC), resulting in a selective accumulation of cGMP in the axons. The axons are also selectively vulnerable to NO toxicity. The experiments initially aimed to determine any causative link between these two effects. It was shown, usi...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.61.1.97

    authors： Garthwaite G,Goodwin DA,Neale S,Riddall D,Garthwaite J

    更新日期：2002-01-01 00:00:00

  • A potent and selective inhibitor of cyclic AMP phosphodiesterase with potential cardiotonic and antithrombotic properties.

    abstract：:Some biochemical and pharmacological properties of a novel, potent inhibitor of cyclic AMP phosphodiesterase, N-cyclohexyl-N-methyl-4-(7-oxy-1,2,3,5-tetrahydroimidazo[2,1-b] quinazolin-2-one) butyramide (RS-82856), were investigated. RS-82856 selectively inhibits the high affinity form of cyclic AMP phosphodiesterase ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Alvarez R,Banerjee GL,Bruno JJ,Jones GL,Littschwager K,Strosberg AM,Venuti MC

    更新日期：1986-06-01 00:00:00

  • Inhibition of Brain Epidermal Growth Factor Receptor Activation: A Novel Target in Neurodegenerative Diseases and Brain Injuries.

    abstract：:Several reports have been published recently demonstrating a beneficial effect of epidermal growth factor receptor (EGFR) inhibitors in improving pathologic and behavioral conditions in neurodegenerative diseases (NDDs) such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS) as well as the brain and spinal...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章,评审

    doi：10.1124/mol.120.119909

    authors： Tavassoly O,Sato T,Tavassoly I

    更新日期：2020-07-01 00:00:00

  • Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1.

    abstract：:The small GTPase Rac1 has been widely implicated in mammary tumorigenesis and metastasis. Previous studies established that stimulation of ErbB receptors in breast cancer cells activates Rac1 and enhances motility via the Rac-guanine nucleotide exchange factor P-Rex1. As the Janus tyrosine kinase 2 (Jak2)/signal trans...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.112.084293

    authors： Lopez-Haber C,Kazanietz MG

    更新日期：2013-05-01 00:00:00

  • Chronic benzodiazepine agonist treatment produces functional uncoupling of the gamma-aminobutyric acid-benzodiazepine receptor ionophore complex in cortical neurons.

    abstract：:We have investigated the effect of chronic flurazepam HCl treatment on the gamma-aminobutyric acid (GABA)A receptor complex in cultured mammalian cortical neurons. Chronic flurazepam (1-5 microM, for 1-10 days) treatment did not produce any changes in the morphological appearance or the cell protein content of cortica...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Hu XJ,Ticku MK

    更新日期：1994-04-01 00:00:00

  • Glycoprotein nature of the A2-adenosine receptor binding subunit.

    abstract：:Mammalian A2-adenosine receptor binding subunits (A2AR) can be visualized by covalent labeling with the photoaffinity crosslinking ligand 125I-2-[4-[2-[2-[(4-aminophenyl)methylcarbonylamino] ethylaminocarbonyl]ethyl]phenyl]ethylamino-5'-N-ethylcarboxamidoad enosine or directly with the azide derivative described in th...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Barrington WW,Jacobson KA,Stiles GL

    更新日期：1990-08-01 00:00:00

  • Hormonal regulation of hepatic organic anion transporting polypeptides.

    abstract：:Organic anion transporting polypeptides (Oatp) mediate the transport of a wide variety of amphipathic organic substrates. Rat Oatp1b2 and human OATP1B3 are members of a liver-specific subfamily of Oatps/OATPs. We investigated whether prolactin (PRL) and growth hormone (GH) regulated Oatp1b2 and OATP1B3 gene expression...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.104.010371

    authors： Wood M,Ananthanarayanan M,Jones B,Wooton-Kee R,Hoffman T,Suchy FJ,Vore M

    更新日期：2005-07-01 00:00:00

  • Increased biliary GSSG efflux from rat livers perfused with thiocarbamide substrates for the flavin-containing monooxygenase.

    abstract：:Thiourea, phenylthiourea, and methimazole perfused into rat liver stimulated the biliary efflux of GSSG without affecting the excretion of GSH into either the bile or the caval perfusate. The thiocarbamide moiety appears essential, since perfusion with urea, phenylurea, or N-methylimidazole did not stimulate GSSG rele...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Krieter PA,Ziegler DM,Hill KE,Burk RF

    更新日期：1984-07-01 00:00:00

  • AMP Kinase Activation Alters Oxidant-Induced Stress Granule Assembly by Modulating Cell Signaling and Microtubule Organization.

    abstract：:Eukaryotic cells assemble stress granules (SGs) when translation initiation is inhibited. Different cell signaling pathways regulate SG production. Particularly relevant to this process is 5'-AMP-activated protein kinase (AMPK), which functions as a stress sensor and is transiently activated by adverse physiologic con...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.116.105494

    authors： Mahboubi H,Koromilas AE,Stochaj U

    更新日期：2016-10-01 00:00:00

  • Structural domains of chimeric dopamine-noradrenaline human transporters involved in the Na(+)- and Cl(-)-dependence of dopamine transport.

    abstract：:Catecholamine transporters constitute the biological targets for several important drugs, including antidepressants, cocaine, and related compounds. Some information exists about discrete domains of these transporters that are involved in substrate translocation and uptake blockade, but delineation of domains mediatin...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.58.6.1404

    authors： Syringas M,Janin F,Mezghanni S,Giros B,Costentin J,Bonnet JJ

    更新日期：2000-12-01 00:00:00

  • Insights into the gating mechanism of the ryanodine-modified human cardiac Ca2+-release channel (ryanodine receptor 2).

    abstract：:Ryanodine receptors (RyRs) are intracellular membrane channels playing key roles in many Ca(2+) signaling pathways and, as such, are emerging novel therapeutic and insecticidal targets. RyRs are so named because they bind the plant alkaloid ryanodine with high affinity and although it is established that ryanodine pro...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.114.093757

    authors： Mukherjee S,Thomas NL,Williams AJ

    更新日期：2014-09-01 00:00:00

  • Differential spatial approximation between cholecystokinin residue 30 and receptor residues in active and inactive conformations.

    abstract：:Understanding the structures of active and inactive agonist- and antagonist-bound receptor complexes is of great interest. In this work, we focus on position 30 of cholecystokinin (CCK) and its spatial approximation with the type A CCK receptor. For this, we developed two photoaffinity labeling probes, replacing the n...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.105.012179

    authors： Dong M,Hadac EM,Pinon DI,Miller LJ

    更新日期：2005-06-01 00:00:00

  • Nanomolar and micromolar effects of 15-deoxy-delta 12,14-prostaglandin J2 on amnion-derived WISH epithelial cells: differential roles of peroxisome proliferator-activated receptors gamma and delta and nuclear factor kappa B.

    abstract：:15-Deoxy delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), an activator of peroxisome proliferator-activated receptor (PPAR)-gamma and -delta, is a prostanoid metabolite with anti-inflammatory actions. In intrauterine tissues, proinflammatory cytokines and prostaglandins have been identified as playing key roles in the ma...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.104.009449

    authors： Berry EB,Keelan JA,Helliwell RJ,Gilmour RS,Mitchell MD

    更新日期：2005-07-01 00:00:00

  • S-nitrosylating agents: a novel class of compounds that increase cystic fibrosis transmembrane conductance regulator expression and maturation in epithelial cells.

    abstract：:The endogenous bronchodilator, S-nitrosoglutathione (GSNO), increases expression, maturation, and function of both the wild-type and the DeltaF508 mutant of the cystic fibrosis transmembrane conductance regulatory protein (CFTR). Though transcriptional mechanisms of action have been identified, GSNO seems also to have...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.106.023242

    authors： Zaman K,Carraro S,Doherty J,Henderson EM,Lendermon E,Liu L,Verghese G,Zigler M,Ross M,Park E,Palmer LA,Doctor A,Stamler JS,Gaston B

    更新日期：2006-10-01 00:00:00

  • Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor.

    abstract：:The cannabinoid analog abnormal cannabidiol [abn-cbd; (-)-4-(3-3,4-trans-p-menthadien-[1,8]-yl)-olivetol] does not bind to CB(1) or CB(2) receptors, yet it acts as a full agonist in relaxing rat isolated mesenteric artery segments. Vasorelaxation by abn-cbd is endothelium-dependent, pertussis toxin-sensitive, and is i...

    journal_title：Molecular pharmacology

    pub_type： 评论,杂志文章

    doi：10.1124/mol.63.3.699

    authors： Offertáler L,Mo FM,Bátkai S,Liu J,Begg M,Razdan RK,Martin BR,Bukoski RD,Kunos G

    更新日期：2003-03-01 00:00:00

  • Mutations within the cholecystokinin-B/gastrin receptor ligand 'pocket' interconvert the functions of nonpeptide agonists and antagonists.

    abstract：:We have reported previously that the transmembrane domains of the cholecystokinin-B/gastrin receptor (CCK-BR) comprise a putative ligand binding pocket. In the present study, we examined whether amino acid substitutions within the CCK-BR pocket altered the affinities and/or functional activities of L-365,260 (the prot...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.54.5.857

    authors： Bläker M,Ren Y,Gordon MC,Hsu JE,Beinborn M,Kopin AS

    更新日期：1998-11-01 00:00:00

  • Role for the regulator of G-protein signaling homology domain of G protein-coupled receptor kinases 5 and 6 in beta 2-adrenergic receptor and rhodopsin phosphorylation.

    abstract：:Phosphorylation of G protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) is a major mechanism of desensitization of these receptors. GPCR activation of GRKs involves an allosteric site on GRKs distinct from the catalytic site. Although recent studies have suggested an important role of the N- and C-termini and do...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.109.058115

    authors： Baameur F,Morgan DH,Yao H,Tran TM,Hammitt RA,Sabui S,McMurray JS,Lichtarge O,Clark RB

    更新日期：2010-03-01 00:00:00

  • Agonist-promoted Lys63-linked polyubiquitination of the human kappa-opioid receptor is involved in receptor down-regulation.

    abstract：:Ubiquitination of the human kappa opioid receptor (hKOR) expressed in Chinese hamster ovary (CHO) cells was observed in the presence of the proteasomal inhibitor N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG132) and enhanced by the agonists (-)(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidiny) cyclohexyl] benzeneaceta...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.107.042846

    authors： Li JG,Haines DS,Liu-Chen LY

    更新日期：2008-04-01 00:00:00

  • Characterization of variant neuroblastoma clones with missing or altered sodium channels.

    abstract：:Variant neuroblastoma cell clones were selected for resistance to the cytotoxic effects of neurotoxins that cause persistent activation of sodium channels. Three classes of variant clones were obtained: sodium channel-deficient clones, which have markedly reduced numbers of functional sodium channels; scorpion toxin-r...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Costa MR,Catterall WA

    更新日期：1982-07-01 00:00:00

  • The inhibitory potency and selectivity of arginine substrate site nitric-oxide synthase inhibitors is solely determined by their affinity toward the different isoenzymes.

    abstract：:We have investigated various nitric oxide (NO) synthase inhibitors for their affinity and selectivity toward the three human isoenzymes in radioligand binding experiments. Therefore, we developed the new radioligand [(3)H]2-amino-4-picoline to measure binding of these compounds to the three human NO synthase (NOS) iso...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Boer R,Ulrich WR,Klein T,Mirau B,Haas S,Baur I

    更新日期：2000-11-01 00:00:00

  • Identification of Peracetylated Quercetin as a Selective 12-Lipoxygenase Pathway Inhibitor in Human Platelets.

    abstract：:The inflammatory response is necessary for the host's defense against pathogens; however, uncontrolled or unregulated production of eicosanoids has been associated with several types of chronic inflammatory diseases. Thus, it is not surprising that enzymes implicated in the production of eicosanoids have been strategi...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.118.113480

    authors： Doucet MS,Jougleux JL,Poirier SJ,Cormier M,Léger JL,Surette ME,Pichaud N,Touaibia M,Boudreau LH

    更新日期：2019-01-01 00:00:00

  • Functional coupling of the beta 2-adrenoceptor to a pertussis toxin-sensitive G protein in cardiac myocytes.

    abstract：:Recently we demonstrated that the effects of beta 2-adrenoceptor (AR) stimulation to augment Ca2+ current (ICa), cytosolic Ca2+ (Cai) transients, and contractility in rat ventricular myocytes are largely dissociated from its effect to increase cellular cAMP levels. This result suggested that beta 2ARs might be coupled...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Xiao RP,Ji X,Lakatta EG

    更新日期：1995-02-01 00:00:00

  • Characterization and selective inhibition of cyclic nucleotide phosphodiesterase isozymes in canine tracheal smooth muscle.

    abstract：:Cyclic nucleotide phosphodiesterases (PDEs) from canine trachealis were characterized with respect to their kinetic properties, sensitivity to selective inhibitors, and subcellular distribution. Extracts from whole tissue homogenates were applied to DEAE-Sepharose anion exchange columns and eluted with a linear sodium...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Torphy TJ,Cieslinski LB

    更新日期：1990-02-01 00:00:00

  • The histone deacetylase inhibitor MGCD0103 has both deacetylase and microtubule inhibitory activity.

    abstract：:Histone deacetylase inhibitors (HDACis) are currently in trial or are in clinical use for the treatment of a number of tumor types. The clinical efficacy of HDACis can be partly attributed to the modulation of the cell cycle by the HDACis. Here, we have examined the effects of N-(2-aminophenyl)-4-((4-pyridin-3-ylpyrim...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.110.065169

    authors： Chia K,Beamish H,Jafferi K,Gabrielli B

    更新日期：2010-09-01 00:00:00

  • Cisplatin in Combination with MDM2 Inhibition Downregulates Rad51 Recombinase in a Bimodal Manner to Inhibit Homologous Recombination and Augment Tumor Cell Kill.

    abstract：:Dysfunction of p53 and resistance to cancer drugs can arise through mutually exclusive overexpression of MDM2 or MDM4. Cisplatin-resistant cells, however, can demonstrate increased binding of both MDM2 and MDM4 to p53 but in absence of cellular overexpression. Whether MDM2 inhibitors alone can activate p53 in these re...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.119.117564

    authors： Xie X,He G,Siddik ZH

    更新日期：2020-04-01 00:00:00

  • Repeated electroconvulsive shock: effect on sodium dependency and regional distribution of opioid-binding sites.

    abstract：:The effects of single and repeated electroconvulsive shock (ECS) on the binding of [3H]diprenorphine to rat brain membranes was studied. Repeated but not single ECS significantly increased the Bmax of [3H]diprenorphine binding when measured in the absence but not in the presence of NaCl. On a regional basis the effect...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Hitzemann RJ,Hitzemann BA,Blatt S,Meyerhoff JL,Tortella FC,Kenner JR,Belenky GL,Holaday JW

    更新日期：1987-05-01 00:00:00

  • P2Y2 receptor activation regulates the expression of acetylcholinesterase and acetylcholine receptor genes at vertebrate neuromuscular junctions.

    abstract：:At the vertebrate neuromuscular junction (nmj), ATP is known to be coreleased with acetylcholine from the synaptic vesicles. We have previously shown that the P2Y1 receptor is localized at the nmj. Here, we extend the findings to show that another nucleotide receptor, P2Y2, is also localized there and with P2Y1 jointl...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.104.003269

    authors： Tung EK,Choi RC,Siow NL,Jiang JX,Ling KK,Simon J,Barnard EA,Tsim KW

    更新日期：2004-10-01 00:00:00

  • Evidence for a PCN-P450 enzyme in chickens and comparison of its development with that of other phenobarbital-inducible forms.

    abstract：:Of four monoclonal antibodies to purified rat liver cytochrome P450s, including those from 3-methylcholanthrene-, phenobarbital-, ethanol-, and pregnenolone-16-alpha-carbonitrile-treated rats, only the monoclonal antibody against pregnenolone-16-alpha-carbonitrile-inducible P450 immunodetected proteins in chicken live...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Lorr NA,Bloom SE,Park SS,Gelboin HV,Miller H,Friedman FK

    更新日期：1989-05-01 00:00:00

  • UR-1505, a new salicylate, blocks T cell activation through nuclear factor of activated T cells.

    abstract：:2-Hydroxy-4(-2,2,3,3,3-pentafluoropropoxy)-benzoic acid (UR-1505), a new molecule chemically related to salicylic acid, has immunomodulator properties and is currently under clinical development for treatment of atopic dermatitis. The present work describes the immunomodulatory profile of UR-1505. UR-1505 targets T ce...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.107.035212

    authors： Román J,de Arriba AF,Barrón S,Michelena P,Giral M,Merlos M,Bailón E,Comalada M,Gálvez J,Zarzuelo A,Ramis I

    更新日期：2007-08-01 00:00:00

  • Fusion proteins with anticoagulant and fibrinolytic properties: functional studies and structural considerations.

    abstract：:In an effort to combine the benefits of fibrinolytics, such as staphylokinase, with those of thrombin inhibitors for the prevention of vessel reocclusion after vascular injury, we have produced several chimeric proteins with plasminogen-activating and thrombin-inhibiting properties. Fusion proteins were constructed co...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.62.2.203

    authors： Icke C,Schlott B,Ohlenschläger O,Hartmann M,Gührs KH,Glusa E

    更新日期：2002-08-01 00:00:00