Evidence map›Paper›PMID 29205034›Full record

ArticleJournal of medicinal chemistry2017

Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N-Methyl-d-aspartate (NMDA) Receptor Antagonist.

Mikko Gynther, Ilaria Proietti Silvestri, Jacob C Hansen, Kasper B Hansen, Tarja Malm, Yevheniia Ishchenko, Younes Larsen, Liwei Han, Silke Kayser, Seppo Auriola and 4 more

Open access · greenAbstract read
In one paragraph

Article in Journal of medicinal chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.5field-weighted citation impact, top 15% 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

10 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Association ofInternational journal of molecular sciences · 2023
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  8. Stereoselective Synthesis of New (2ACS chemical neuroscience · 2020
    Article
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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

14 authors at 3 institutions in 3 countries.

Mikko GyntherSchool of Pharmacy, Faculty of Health Sciences, University of Eastern Finland , 70211 Kuopio, Finland.
Ilaria Proietti SilvestriDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen 2100, Denmark.
Jacob C HansenDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen 2100, Denmark.
Kasper B HansenDepartment of Biomedical and Pharmaceutical Sciences and Center for Biomolecular Structure and Dynamics, University of Montana , Missoula, Montana 59812, United States.ORCID 0000-0002-3303-4819
Tarja MalmDepartment of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland , 70211 Kuopio, Finland.
Yevheniia IshchenkoDepartment of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland , 70211 Kuopio, Finland.
Younes LarsenDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen 2100, Denmark.
Liwei HanDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen 2100, Denmark.
Silke KayserDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen 2100, Denmark.
Seppo AuriolaSchool of Pharmacy, Faculty of Health Sciences, University of Eastern Finland , 70211 Kuopio, Finland.
Aleksanteri PetsaloSchool of Pharmacy, Faculty of Health Sciences, University of Eastern Finland , 70211 Kuopio, Finland.
Birgitte NielsenDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen 2100, Denmark.
Darryl S PickeringDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen 2100, Denmark.ORCID 0000-0001-8687-6094
Lennart BunchDepartment of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen 2100, Denmark.ORCID 0000-0002-0180-4639
University of Copenhagen · DKUniversity of Eastern Finland · FIUniversity of Montana · US

Funding

Surveillance genome sequencing to detect SARS-CoV-2 virus variants in MontanaP20GM103546 · NIGMS · UNIVERSITY OF MONTANA · PI BOWLER, BRUCE E · 2012 to 2021
$19.2M
Structural and functional investigation of negative allosteric NMDA receptor modulationR01NS097536 · NINDS · UNIVERSITY OF MONTANA · PI Kasper Boe Hansen · 2016 to 2026
$3.4M
NIGMS NIH HHS P20 GM103546NINDS NIH HHS R01 NS097536
6 · The paper itself

Abstract

The most common solid tumors show intrinsic multidrug resistance (MDR) or inevitably acquire such when treated with anticancer drugs. In this work, we describe the discovery of a peripherally restricted, potent, competitive NMDA receptor antagonist 1l by a structure-activity study of the broad-acting ionotropic glutamate receptor antagonist 1a. Subsequently, we demonstrate that 1l augments the cytotoxic action of sorafenib in murine hepatocellular carcinoma cells. The underlying biological mechanism was shown to be interference with the lipid signaling pathway, leading to reduced expression of MDR transporters and thereby an increased accumulation of sorafenib in the cancer cells. Interference with lipid signaling pathways by NMDA receptor inhibition is a novel and promising strategy for reversing transporter-mediated chemoresistance in cancer cells.

Indexed as

AnimalsAntineoplastic AgentsCarcinoma, HepatocellularCell Line, TumorDrug DiscoveryDrug Resistance, MultipleHumansLiver NeoplasmsMiceNiacinamidePhenylurea CompoundsReceptors, N-Methyl-D-AspartateSorafenibAntineoplastic AgentsNiacinamidePhenylurea CompoundsReceptors, N-Methyl-D-AspartateSorafenib

Identifiers

PMID29205034
PMCPMC5788303
OpenAlexW2771774234

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.