Evidence map›Paper›PMID 30718665›Full record

ArticleScientific reports2019

Oxo-aglaiastatin-Mediated Inhibition of Translation Initiation.

Rayelle Itoua Maïga, Regina Cencic, Jennifer Chu, Daniel D Waller, Lauren E Brown, William G Devine, Wenhan Zhang, Michael Sebag, John A Porco, Jerry Pelletier

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 32% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Comparative phytochemistry of flavaglines (= rocaglamides), a group of highly bioactive flavolignans fromPhytochemistry reviews : proceedings of the Phytochemical Society of Europe · 2022
    Review
  3. Article
  4. Review
  5. MYC inhibitors in multiple myeloma.Cancer drug resistance (Alhambra, Calif.) · 2021
    Review
  6. 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 3 institutions in 2 countries.

Rayelle Itoua MaïgaDepartment of Biochemistry, McGill University, Montreal, Québec, H3G 1Y6, Canada.
Regina CencicDepartment of Biochemistry, McGill University, Montreal, Québec, H3G 1Y6, Canada.
Jennifer ChuDepartment of Biochemistry, McGill University, Montreal, Québec, H3G 1Y6, Canada.
Daniel D WallerDepartment of Medicine, McGill University, Montreal, Québec, H3G 1Y6, Canada.
Lauren E BrownDepartment of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University, Boston, MA, 02215, USA.ORCID 0000-0001-9489-484X
William G DevineDepartment of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University, Boston, MA, 02215, USA.
Wenhan ZhangDepartment of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University, Boston, MA, 02215, USA.
Michael SebagDepartment of Medicine, McGill University, Montreal, Québec, H3G 1Y6, Canada.
John A PorcoDepartment of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University, Boston, MA, 02215, USA.
Jerry PelletierDepartment of Biochemistry, McGill University, Montreal, Québec, H3G 1Y6, Canada. jerry.pelletier@mcgill.ca.
McGill University · CABoston University · USMcGill University Health Centre · CA

Funding

Chemical Synthesis of Complex Natural Products for Translational ScienceR35GM118173 · NIGMS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI JOHN A. PORCO · 2016 to 2026
$8.2M
Center for Molecular Discovery (CMD): A Small Molecule Resource for Biomedical ResearchR24GM111625 · NIGMS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI PORCO, JOHN A. · 2015 to 2017
$1.5M
CIHR FDN-148366NIGMS NIH HHS R24 GM111625NIGMS NIH HHS R35 GM118173
6 · The paper itself

Abstract

Translation is a highly regulated process that is perturbed in human cancers, often through activation of the PI3K/mTOR pathway which impacts directly on the ribosome recruitment phase of translation initiation. While significant research has focused on "drugging" components of the PI3K/mTOR network, efforts have also been directed towards inhibiting eukaryotic initiation factor (eIF) 4F-dependent translation. Small molecule inhibitors of this complex have been identified, characterized, and used to validate the rationale of targeting this step to curtail tumor cell growth and modulate chemotherapy response. One such class of compounds are the rocaglates, secondary metabolites from the plant genus Aglaia, which target the RNA helicase subunit of eIF4F, eIF4A. Here we explore the ability of synthetic derivatives of aglaiastatins and an aglaroxin derivative to target the translation process in vitro and in vivo and find the synthetic derivative oxo-aglaiastatin to possess such activity. Oxo-aglaiastatin inhibited translation in vitro and in vivo and synergized with doxorubicin, ABT-199 (a Bcl-2 antagonist), and dexamethasone when tested on hematological cancer cells. The biological activity of oxo-aglaiastatin was shown to be a consequence of inhibiting eIF4A1 activity.

Indexed as

AglaiaAnimalsAntineoplastic AgentsAntineoplastic Agents, PhytogenicBridged Bicyclo Compounds, HeterocyclicCell Line, TumorDoxorubicinDrug SynergismEukaryotic Initiation Factor-4AFemaleHumansLymphomaMice, Inbred C57BLNeoplasmsPeptide Chain Initiation, TranslationalSulfonamidesAntineoplastic AgentsAntineoplastic Agents, PhytogenicBridged Bicyclo Compounds, HeterocyclicDoxorubicinEIF4A1 protein, humanEukaryotic Initiation Factor-4ASulfonamidesvenetoclax

Identifiers

PMID30718665
PMCPMC6361980
OpenAlexW2914614874

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.