Identification and selectivity profiling of small-molecule degraders via multi-omics approaches.
| Autor: | Scholes NS; CeMM - Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria., Mayor-Ruiz C; CeMM - Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria; IRB Barcelona - Institute for Research in Biomedicine, 08028 Barcelona, Spain., Winter GE; CeMM - Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria. Electronic address: gwinter@cemm.oeaw.ac.at. |
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| Jazyk: | angličtina |
| Zdroj: | Cell chemical biology [Cell Chem Biol] 2021 Jul 15; Vol. 28 (7), pp. 1048-1060. Date of Electronic Publication: 2021 Apr 02. |
| DOI: | 10.1016/j.chembiol.2021.03.007 |
| Abstrakt: | The therapeutic modality of targeted protein degradation promises to overcome limitations of traditional pharmacology. Small-molecule degraders recruit disease-causing proteins to E3 ubiquitin ligases, prompting their ubiquitination and degradation by the proteasome. The discovery, mechanistic elucidation, and selectivity profiling of novel degraders are often conducted in cellular systems. This highlights the need for unbiased multi-omics strategies that inform on the functionally involved components. Here, we review how proteomics and functional genomics can be integrated to identify and mechanistically understand degraders, their target selectivity as well as putative resistance mechanisms. Competing Interests: Declaration of interests G.E.W. is a founder and shareholder of Proxygen and Solgate Therapeutics and coordinates a research collaboration between CeMM and Pfizer. The other authors declare no competing interests. (Copyright © 2021 Elsevier Ltd. All rights reserved.) |
| Databáze: | MEDLINE |
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