Evidence map›Paper›PMID 24675136›Full record

ArticleEuropean journal of medicinal chemistry2014

Structure-activity relationship study of 4EGI-1, small molecule eIF4E/eIF4G protein-protein interaction inhibitors.

Khuloud Takrouri, Ting Chen, Evangelos Papadopoulos, Rupam Sahoo, Eihab Kabha, Han Chen, Sonia Cantel, Gerhard Wagner, Jose A Halperin, Bertal H Aktas and 1 more

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

Article in European journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

9 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Signalling to eIF4E in cancer.Biochemical Society transactions · 2015
    Review
  8. Article
  9. 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

11 authors at 2 institutions in 2 countries.

Khuloud TakrouriLaboratory for Translational Research, Hematology, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Thorn 7, Boston, MA 02115, USA.
Ting ChenLaboratory for Translational Research, Hematology, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Thorn 7, Boston, MA 02115, USA.
Evangelos PapadopoulosDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Rupam SahooLaboratory for Translational Research, Hematology, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Thorn 7, Boston, MA 02115, USA.
Eihab KabhaLaboratory for Translational Research, Harvard Medical School, USA.
Han ChenLaboratory for Translational Research, Harvard Medical School, USA.
Sonia CantelLaboratory for Translational Research, Harvard Medical School, USA.
Gerhard WagnerDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Jose A HalperinLaboratory for Translational Research, Hematology, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Thorn 7, Boston, MA 02115, USA.
Bertal H AktasLaboratory for Translational Research, Hematology, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Thorn 7, Boston, MA 02115, USA.
Michael ChorevLaboratory for Translational Research, Hematology, Brigham and Women's Hospital, Harvard Medical School, 20 Shattuck Street, Thorn 7, Boston, MA 02115, USA. Electronic address: michael_chorev@hms.harvard.edu.
Harvard University · USInstitut des Biomolécules Max Mousseron · FR

Funding

Development of Translation Initiation Inhibitors and their Anti-Cancer ActivityR01CA121357 · NCI · HARVARD MEDICAL SCHOOL · PI CHOREV, MICHAEL · 2008 to 2012
$1.7M
NCI NIH HHS R01 CA121357NCI NIH HHS R01CA121357
6 · The paper itself

Abstract

Protein-protein interactions are critical for regulating the activity of translation initiation factors and multitude of other cellular process, and form the largest block of untapped albeit most challenging targets for drug development. 4EGI-1, (E/Z)-2-(2-(4-(3,4-dichlorophenyl)thiazol-2-yl)hydrazono)-3-(2-nitrophenyl)propanoic acid, is a hit compound discovered in a screening campaign of small molecule libraries as an inhibitor of translation initiation factors eIF4E and eIF4G protein-protein interaction; it inhibits translation initiation in vitro and in vivo. A series of 4EGI-1-derived thiazol-2-yl hydrazones have been designed and synthesized in order to delineate the structural latitude and improve its binding affinity to eIF4E, and increase its potency in inhibiting the eIF4E/eIF4G interaction. Probing a wide range of substituents on both phenyl rings comprising the 3-phenylpropionic acid and 4-phenylthiazolidine moieties in the context of both E- and Z-isomers of 4EGI-1 led to analogs with enhanced binding affinity and translation initiation inhibitory activities.

Indexed as

Cell Line, TumorDose-Response Relationship, DrugEukaryotic Initiation Factor-4GHumansHydrazonesMolecular StructureNucleocytoplasmic Transport ProteinsProtein BindingStructure-Activity RelationshipThiazoles4EGI-1 compoundEIF4ENIF1 protein, humanEIF4G1 protein, humanEukaryotic Initiation Factor-4GHydrazonesNucleocytoplasmic Transport ProteinsThiazoles4EGI-1eIF4FE/Z-isomerizationFlorescence polarization assayHydrazonesInhibitors of protein–protein interactionThiazol-2-yl hydrazonesTranslation initiation

Identifiers

PMID24675136
PMCPMC4128255
OpenAlexW2068809549

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.