Evidence map›Paper›PMID 33167327›Full record

ArticleInternational journal of molecular sciences2020

Dual-Inhibitors of N-Myc and AURKA as Potential Therapy for Neuroendocrine Prostate Cancer.

Anh-Tien Ton, Kriti Singh, Hélène Morin, Fuqiang Ban, Eric Leblanc, Joseph Lee, Nada Lallous, Artem Cherkasov

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

Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.6field-weighted citation impact, top 19% 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

14 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Targeting Key Players of Neuroendocrine Differentiation in Prostate Cancer.International journal of molecular sciences · 2023
    Review
  6. Review
  7. Article
  8. The Essential Oil fromPharmaceuticals (Basel, Switzerland) · 2022
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. 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

8 authors at 1 institution in 2 countries.

Anh-Tien TonVancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada.ORCID 0000-0001-7418-6563
Kriti SinghVancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada.
Hélène MorinVancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada.
Fuqiang BanVancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada.
Eric LeblancVancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada.ORCID 0000-0003-1838-7277
Joseph LeeVancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada.
Nada LallousVancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada.ORCID 0000-0002-8665-8641
Artem CherkasovVancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, BC V6H 3Z6, Canada.
University of British Columbia · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Resistance to androgen-receptor (AR) directed therapies is, among other factors, associated with Myc transcription factors that are involved in development and progression of many cancers. Overexpression of N-Myc protein in prostate cancer (PCa) leads to its transformation to advanced neuroendocrine prostate cancer (NEPC) that currently has no approved treatments. N-Myc has a short half-life but acts as an NEPC stimulator when it is stabilized by forming a protective complex with Aurora A kinase (AURKA). Therefore, dual-inhibition of N-Myc and AURKA would be an attractive therapeutic avenue for NEPC. Following our computer-aided drug discovery approach, compounds exhibiting potent N-Myc specific inhibition and strong anti-proliferative activity against several N-Myc driven cell lines, were identified. Thereafter, we have developed dual inhibitors of N-Myc and AURKA through structure-based drug design approach by merging our novel N-Myc specific chemical scaffolds with fragments of known AURKA inhibitors. Favorable binding modes of the designed compounds to both N-Myc and AURKA target sites have been predicted by docking. A promising lead compound, 70812, demonstrated low-micromolar potency against both N-Myc and AURKA in vitro assays and effectively suppressed NEPC cell growth.

Indexed as

Antineoplastic AgentsAurora Kinase ACarcinoma, NeuroendocrineCell Line, TumorCells, CulturedDrug DiscoveryDrug Screening Assays, AntitumorDrugs, InvestigationalHumansMaleModels, MolecularMolecular Docking SimulationMolecular Targeted TherapyN-Myc Proto-Oncogene ProteinProstatic NeoplasmsProtein Kinase InhibitorsAntineoplastic AgentsAR protein, humanAURKA protein, humanAurora Kinase ADrugs, InvestigationalMYCN protein, humanN-Myc Proto-Oncogene ProteinProtein Kinase InhibitorsReceptors, Androgenaurora a kinasedrug discoverydual inhibitorMycpolypharmacologyprostate cancer

Identifiers

PMID33167327
PMCPMC7663809
OpenAlexW3095801526

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.