2. Academic Validation
  3. The identification of functional regions of MEK1 using CRISPR tiling screens

The identification of functional regions of MEK1 using CRISPR tiling screens

  • Commun Biol. 2025 Apr 24;8(1):656. doi: 10.1038/s42003-025-07966-4.
Zhiqiang Zhang 1 2,  Barbara Abreu 3 4,  Jessica L Brothwood 3,  John Alexander 3,  Martin J Sims 3,  John F Lyons 3,  Joanne M Munck 3,  Christopher J Hindley 3 5
Affiliations

Affiliations

  • 1 Astex Pharmaceuticals, Cambridge, UK. zz5@sanger.ac.uk.
  • 2 Wellcome Sanger Institute, Hinxton, UK. zz5@sanger.ac.uk.
  • 3 Astex Pharmaceuticals, Cambridge, UK.
  • 4 School of Life Sciences, University of Warwick, Coventry, UK.
  • 5 Insmed Innovation UK Ltd, Cambridge, UK.
PMID: 40274952 DOI: 10.1038/s42003-025-07966-4
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.

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