Evidence map›Paper›PMID 40274952›Full record

ArticleCommunications biology2025

The identification of functional regions of MEK1 using CRISPR tiling screens.

Zhiqiang Zhang, Barbara Abreu, Jessica L Brothwood, John Alexander, Martin J Sims, John F Lyons, Joanne M Munck, Christopher J Hindley

Abstract read
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In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Zhiqiang ZhangAstex Pharmaceuticals, Cambridge, UK. zz5@sanger.ac.uk.ORCID http://orcid.org/0000-0002-3855-8101
Barbara AbreuAstex Pharmaceuticals, Cambridge, UK.
Jessica L BrothwoodAstex Pharmaceuticals, Cambridge, UK.
John AlexanderAstex Pharmaceuticals, Cambridge, UK.
Martin J SimsAstex Pharmaceuticals, Cambridge, UK.ORCID http://orcid.org/0009-0001-8684-6095
John F LyonsAstex Pharmaceuticals, Cambridge, UK.
Joanne M MunckAstex Pharmaceuticals, Cambridge, UK.
Christopher J HindleyAstex Pharmaceuticals, Cambridge, UK.ORCID http://orcid.org/0000-0002-5294-1270

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CRISPR tiling screen is a powerful tool to identify protein regions relevant to its biological function. Understanding the functional relevance of the regions of target protein is of great help for structure-based drug discovery. Studying the drug resistance mechanisms of small-molecule inhibitors is important for the development and clinical application of the compounds. Using MEK1 and MEK inhibitors as example here, we demonstrate the utility of CRISPR tiling to identify regions essential for cancer cell viability and regions where mutations are resistant to MEK inhibitors. We study the drug resistance mechanisms of the regions and discussed the potential, as well as limitations, of applying the technology to drug development. Our findings demonstrate the value and prompt the utilization of CRISPR tiling technology in structure-based drug discovery.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsMAP Kinase Kinase 1Cell Line, TumorCell SurvivalDrug DiscoveryDrug Resistance, NeoplasmHumansMutationProtein Kinase InhibitorsMAP2K1 protein, humanMAP Kinase Kinase 1Protein Kinase Inhibitors

Identifiers

PMID40274952
PMCPMC12022096

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Registered trials

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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.