Evidence map›Paper›PMID 24424130›Full record

ArticleBioorganic & medicinal chemistry letters2014

The development of benzo- and naphtho-fused quinoline-2,4-dicarboxylic acids as vesicular glutamate transporter (VGLUT) inhibitors reveals a possible role for neuroactive steroids.

Christina N Carrigan, Sarjubhai A Patel, Holly D Cox, Erin S Bolstad, John M Gerdes, Wesley E Smith, Richard J Bridges, Charles M Thompson

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 41% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. VGLUT substrates and inhibitors: A computational viewpoint.Biochimica et biophysica acta. Biomembranes · 2020
    Review
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Christina N CarriganCenter for Structural and Functional Neuroscience, Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, MT 59812, USA.
Sarjubhai A PatelCenter for Structural and Functional Neuroscience, Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, MT 59812, USA.
Holly D CoxCenter for Structural and Functional Neuroscience, Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, MT 59812, USA.
Erin S BolstadCenter for Structural and Functional Neuroscience, Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, MT 59812, USA.
John M GerdesCenter for Structural and Functional Neuroscience, Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, MT 59812, USA.
Wesley E SmithCenter for Structural and Functional Neuroscience, Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, MT 59812, USA.
Richard J BridgesCenter for Structural and Functional Neuroscience, Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, MT 59812, USA.
Charles M ThompsonCenter for Structural and Functional Neuroscience, Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, MT 59812, USA. Electronic address: charles.thompson@umontana.edu.
University of Montana · US

Funding

Understanding the molecular mechanism of pathogenesis of prion diseasesP20RR015583 · NCRR · UNIVERSITY OF MONTANA · PI KAVANAUGH, MICHAEL PATRICK · 2000 to 2009
$17.6M
Core Laboratory for Neuromolecular ProductionP30NS055022 · NINDS · UNIVERSITY OF MONTANA · PI THOMPSON, CHARLES MARK · 2008 to 2013
$4.2M
VESICULAR GLUTAMATE TRANSPORT--PHARMACOPHORE ELUCIDATIONR01NS038248 · NINDS · UNIVERSITY OF MONTANA · PI THOMPSON, CHARLES MARK · 1999 to 2006
$1.8M
Vesicular Glutamate Transport: Neurosteroid RegulationR21NS042077 · NINDS · UNIVERSITY OF MONTANA · PI BRIDGES, RICHARD J. · 2001 to 2002
$275k
NCRR NIH HHS P20 RR015583NCRR NIH HHS P20-RR15583NINDS NIH HHS P30 NS-055022NINDS NIH HHS P30 NS055022NINDS NIH HHS R01 NS038248NINDS NIH HHS R01-NS38248NINDS NIH HHS R21 NS042077NINDS NIH HHS R21-NS42077
6 · The paper itself

Abstract

Substituted quinoline-2,4-dicarboxylates (QDCs) are conformationally-restricted mimics of glutamate that were previously reported to selectively block the glutamate vesicular transporters (VGLUTs). We find that expanding the QDC scaffold to benzoquinoline dicarboxylic acids (BQDC) and naphthoquinoline dicarboxylic acids (NQDCs) improves inhibitory activity with the NQDCs showing IC50∼70 μM. Modeling overlay studies showed that the polycyclic QDCs resembled steroid structures and led to the identification and testing of estrone sulfate, pregnenolone sulfate and pregnanolone sulfate that blocked the uptake of l-Glu by 50%, 70% and 85% of control, respectively. Pregnanolone sulfate was further characterized by kinetic pharmacological determinations that demonstrated competitive inhibition and a Ki of ≈20 μM.

Indexed as

Binding, CompetitiveCyclizationDicarboxylic AcidsDose-Response Relationship, DrugInhibitory Concentration 50Models, MolecularMolecular StructureNaphtholsNeurotransmitter AgentsPregnanoloneQuinolinesReference StandardsVesicular Glutamate Transport ProteinsDicarboxylic AcidsNaphtholsNeurotransmitter AgentsPregnanoloneQuinolinesVesicular Glutamate Transport ProteinsGlutamateNeuroactive steroidsQuinoline 2,4-dicarboxylic acidSynaptic vesicleVGLUT

Identifiers

PMID24424130
PMCPMC3943356
OpenAlexW2088444896

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.