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田邊 賢司
Department Research Institutes and Facilities, Research Institutes and Facilities Position Associate Professor |
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| Article types | Original article |
| Language | English |
| Peer review | Non peer reviewed |
| Title | Image-based phenotypic profiling of a chemogenomic screening library identifies novel druggable targets in the EGFR pathway |
| Journal | Formal name：BioRxiv |
| Domestic / Foregin | Foregin |
| Volume, Issue, Page | pp.440090 |
| Author and coauthor | Kenji Tanabe |
| Authorship | Lead author,Corresponding author |
| Publication date | 2021/04/17 |
| Summary | The gene encoding epidermal growth factor receptor (EGFR) is a major driver gene in cancer. Many drugs targeting EGFR-associated molecules have been developed, yet many have failed in clinical trials due to a lack of efficacy and/or unexpected side effects. In this study, I used image-based phenotypic profiling to screen a pharmacologically active compound library with the aim of identifying new druggable targets in the EGFR pathway. As anticipated, the phenotypic screen identified compounds that produce phenotypes resulting from targeting a known specific molecule or pathway. The assay also showed that compounds with diverse known mechanisms of action produced similar, EGFR-related cellular phenotypes. Biochemical assays revealed that those compounds share a previously unappreciated common target/pathway, showing that the image-based assay can identify new target molecules that are independent of the compound's known target. Further experiments showed that ROCK1 and PSMD2 are novel druggable targets within the EGFR pathway. |
| DOI | https://doi.org/10.1101/2021.04.16.440090 |