Polycomb Repressive Complex 2 Modulation through the Development of EZH2-EED Interaction Inhibitors and EED Binders
| Autor: | Stefano Tomassi, Annalisa Romanelli, Sergio Valente, Antonello Mai, Clemens Zwergel |
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| Přispěvatelé: | Tomassi, S., Romanelli, A., Zwergel, C., Valente, S., Mai, A. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Tazemetostat
Antineoplastic Agents macromolecular substances Computational biology epigenetics polycomb repressive complex 2 EZH2−EED interaction inhibitors EED binders Antineoplastic Agent Neoplasms Cell Line Tumor Drug Discovery Animals Humans Enzyme Inhibitor Enhancer of Zeste Homolog 2 Protein Epigenetics PRC2 complex Enzyme Inhibitors biology Chemistry Animal EZH2 Polycomb Repressive Complex 2 Perspective biology.protein Molecular Medicine Neoplasm PRC2 Human Protein Binding |
| Zdroj: | Journal of Medicinal Chemistry |
| Popis: | Epigenetics is nowadays a well-accepted area of research. In the last years, tremendous progress was made regarding molecules targeting EZH2, directly or indirectly. Recently tazemetostat hit the market after FDA-approval for the treatment of lymphoma. However, the impairment of EZH2 activity by orthosteric intervention has proven to be effective only in a limited subset of cancers. Considering the multiproteic nature of the PRC2 complex and the marked dependence of EZH2 functions on the other core subunits such as EED, in recent years, a new targeting approach ascended to prominence. The possibility to cripple the function of the PRC2 complex by interfering with its multimeric integrity fueled the interest in developing EZH2-EED protein-protein interaction and EED inhibitors as indirect modulators of PRC2-dependent methyltransferase activity. In this Perspective, we aim to summarize the latest findings regarding the development and the biological activity of these emerging classes of PRC2 modulators from a medicinal chemist's viewpoint. |
| Databáze: | OpenAIRE |
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