Evidence map›Paper›PMID 24403123›Full record

ArticleCancer medicine2014

Identification of novel candidate compounds targeting TrkB to induce apoptosis in neuroblastoma.

Yohko Nakamura, Akiko Suganami, Mayu Fukuda, Md Kamrul Hasan, Tomoki Yokochi, Atsushi Takatori, Shunpei Satoh, Tyuji Hoshino, Yutaka Tamura, Akira Nakagawara

Open access · goldAbstract read
In one paragraph

Article in Cancer medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

15 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Frontiers in pharmacology · 2024
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Neuroblastoma treatment in the post-genomic era.Journal of biomedical science · 2017
    Review
  14. Article
  15. Article
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

10 authors at 2 institutions in 1 country.

Yohko NakamuraDivision of Biochemistry and Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Chiba, 260-8717, Japan.
Akiko Suganami
Mayu Fukuda
Md Kamrul Hasan
Tomoki Yokochi
Atsushi Takatori
Shunpei Satoh
Tyuji Hoshino
Yutaka Tamura
Akira Nakagawara
Chiba Cancer Center · JPChiba University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neuroblastoma (NB) is one of the most frequent solid tumors in children and its prognosis is still poor. The neurotrophin receptor TrkB and its ligand brain-derived neurotrophic factor (BDNF) are expressed at high levels in high-risk NBs and are involved in defining the poor prognosis of the patients. However, the TrkB targeting therapy has never been realized in the clinic. We performed an in silico screening procedure utilizing an AutoDock/grid computing technology in order to identify novel small chemical compounds targeting the BDNF-binding domain of TrkB. For the first screening, a library of three million synthetic compounds was screened in silico and was ranked according to the Docking energy. The top-ranked 37 compounds were further functionally screened for cytotoxicity by using NB cell lines. We have finally identified seven compounds that kill NB cells with the IC50 values of 0.07-4.6 μmol/L. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed that these molecules induce apoptosis accompanied by p53 activation in NB cell lines. The candidate compounds and BDNF demonstrated an antagonistic effect on cell growth, invasion, and colony formation, possibly suggesting competition at the BDNF-binding site of TrkB. The candidate compounds had tumor-suppressive activity in xenograft and in vivo toxicity tests (oral and intravenous administrations) using mice, and did not show any abnormal signs. Using in silico Docking screening we have found new candidate TrkB inhibitors against high-risk NBs, which could lead to new anti-cancer drugs.

Indexed as

AnimalsAntineoplastic AgentsApoptosisBrain-Derived Neurotrophic FactorCell Line, TumorGene Expression Regulation, NeoplasticHumansMembrane GlycoproteinsMiceMolecular Docking SimulationNeuroblastomaProtein KinasesProtein-Tyrosine KinasesReceptor, trkBSignal TransductionSmall Molecule LibrariesAntineoplastic AgentsBDNF protein, humanBrain-Derived Neurotrophic FactorMembrane GlycoproteinsProtein KinasesProtein-Tyrosine KinasesReceptor, trkBSmall Molecule Librariestropomyosin-related kinase-B, humanBDNFdrug discoveryin silico simulationsneuroblastomaTrkB

Identifiers

PMID24403123
PMCPMC3930387
OpenAlexW2140493919

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.