Evidence map›Paper›PMID 29989546›Full record

ArticleeLife2018

BRET-based RAS biosensors that show a novel small molecule is an inhibitor of RAS-effector protein-protein interactions.

Nicolas Bery, Abimael Cruz-Migoni, Carole Jr Bataille, Camilo E Quevedo, Hanna Tulmin, Ami Miller, Angela Russell, Simon Ev Phillips, Stephen B Carr, Terence H Rabbitts

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

44 citing papers in PubMed, 60 citations in OpenAlex.

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  16. Fluorescent Biosensor for Measuring Ras Activity in Living Cells.Journal of the American Chemical Society · 2022
    Article
  17. Article
  18. Antibody-Based Approaches to Target Pancreatic Tumours.Antibodies (Basel, Switzerland) · 2022
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Nicolas BeryMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.ORCID http://orcid.org/0000-0002-2643-3897
Abimael Cruz-MigoniMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
Carole Jr BatailleChemistry Research Laboratory, Oxford, United Kingdom.
Camilo E QuevedoMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
Hanna TulminMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
Ami MillerMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
Angela RussellChemistry Research Laboratory, Oxford, United Kingdom.
Simon Ev PhillipsDepartment of Biochemistry, University of Oxford, Oxford, United Kingdom.
Stephen B CarrResearch Complex at Harwell, Rutherford Appleton Laboratory, Didcot, United Kingdom.
Terence H RabbittsMRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.ORCID http://orcid.org/0000-0002-4982-2609
University of Oxford · GBRutherford Appleton Laboratory · GBCentre for Human Genetics · GB

Funding

Bloodwise 12051Medical Research Council MR/J000612/1Wellcome TrustWellcome Trust 099246/Z/12/ZWellcome Trust 100842/Z/12/Z
6 · The paper itself

Abstract

The RAS family of proteins is amongst the most highly mutated in human cancers and has so far eluded drug therapy. Currently, much effort is being made to discover mutant RAS inhibitors and in vitro screening for RAS-binding drugs must be followed by cell-based assays. Here, we have developed a robust set of bioluminescence resonance energy transfer (BRET)-based RAS biosensors that enable monitoring of RAS-effector interaction inhibition in living cells. These include KRAS, HRAS and NRAS and a variety of different mutations that mirror those found in human cancers with the major RAS effectors such as CRAF, PI3K and RALGDS. We highlighted the utility of these RAS biosensors by showing a RAS-binding compound is a potent pan-RAS-effector interactions inhibitor in cells. The RAS biosensors represent a useful tool to investigate and characterize the potency of anti-RAS inhibitors in cells and more generally any RAS protein-protein interaction (PPI) in cells.

Indexed as

MutationProtein Interaction Domains and MotifsBioluminescence Resonance Energy Transfer TechniquesBiosensing TechniquesEnergy TransferHEK293 CellsHumansProtein BindingProto-Oncogene Proteins p21(ras)Signal TransductionSmall Molecule LibrariesProto-Oncogene Proteins p21(ras)Small Molecule LibrariesbiosensorsBRETcancercancer biologycell-based assaysdrug developmenthumanintracellular antibodymouseprotein-protein interaction inhibitionRASsmall molecule inhibitors

Identifiers

PMID29989546
PMCPMC6039175
OpenAlexW2844895840

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.