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Drug Discovery Approaches to Target E3 Ligases
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Targeting E3 ligases is a challenging area in drug discovery. Despite the human genome encoding for more than 600 E3 ubiquitin ligases, only a handful of E3 ligases have been pharmacologically modulated or exploited for targeted protein degradation (TPD) strategies. The main obstacle for hijacking these E3 ligases is the lack of small-molecule ligands. As research into this field advances, the identification of new small molecules capable of binding to E3 ligases has become an essential pursuit. These ligases not only expand the repertoire of druggable targets but also offer the potential for increased specificity and selectivity in protein degradation. The synergy between academia and industry is key, as it combines academic expertise in fundamental research with the industrial capabilities of translating these findings into novel therapeutics. In this review, we provide an overview of the different strategies employed in academia and industry to the discovery of new E3 ligases ligands, showing them with illustrative cases.
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RODRÍGUEZ GIMENO, Alejandra and GALDEANO CANTADOR, Carloss. Drug Discovery Approaches to Target E3 Ligases. ChemBioChem. 2024. Vol. 26, num. 1, pags. e202400656. ISSN 1439-4227. [consulted: 6 of October of 2026]. Available at: https://hdl.handle.net/2445/229518