| Autor: |
Duncan Holbrook‐Smith, Stephan Durot, Uwe Sauer |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Molecular Systems Biology, Vol 18, Iss 2, Pp 1-16 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1744-4292 |
| DOI: |
10.15252/msb.202110767 |
| Popis: |
Abstract Chemical probes are important tools for understanding biological systems. However, because of the huge combinatorial space of targets and potential compounds, traditional chemical screens cannot be applied systematically to find probes for all possible druggable targets. Here, we demonstrate a novel concept for overcoming this challenge by leveraging high‐throughput metabolomics and overexpression to predict drug–target interactions. The metabolome profiles of yeast treated with 1,280 compounds from a chemical library were collected and compared with those of inducible yeast membrane protein overexpression strains. By matching metabolome profiles, we predicted which small molecules targeted which signaling systems and recovered known interactions. Drug–target predictions were generated across the 86 genes studied, including for difficult to study membrane proteins. A subset of those predictions were tested and validated, including the novel targeting of GPR1 signaling by ibuprofen. These results demonstrate the feasibility of predicting drug–target relationships for eukaryotic proteins using high‐throughput metabolomics. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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