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Anticancer Small-Molecule Agents Targeting Eukaryotic Elongation Factor 1A: State of the Art
Eukaryotic elongation factor 1A (eEF1A) canonically delivers amino acyl tRNA to the ribosomal A site during the elongation stage of protein biosynthesis. Yet paradoxically, the oncogenic nature of this instrumental protein has long been recognized. Consistently, eEF1A has proven to be targeted by a...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10049629/ https://www.ncbi.nlm.nih.gov/pubmed/36982256 http://dx.doi.org/10.3390/ijms24065184 |
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author | Zhang, Han Cai, Jiayou Yu, Siqi Sun, Bin Zhang, Weicheng |
author_facet | Zhang, Han Cai, Jiayou Yu, Siqi Sun, Bin Zhang, Weicheng |
author_sort | Zhang, Han |
collection | PubMed |
description | Eukaryotic elongation factor 1A (eEF1A) canonically delivers amino acyl tRNA to the ribosomal A site during the elongation stage of protein biosynthesis. Yet paradoxically, the oncogenic nature of this instrumental protein has long been recognized. Consistently, eEF1A has proven to be targeted by a wide assortment of small molecules with excellent anticancer activity, among which plitidepsin has been granted approval for the treatment of multiple myeloma. Meanwhile, metarrestin is currently under clinical development for metastatic cancers. Bearing these exciting advances in mind, it would be desirable to present a systematic up-to-date account of the title topic, which, to the best of our knowledge, has thus far been unavailable in the literature. The present review summarizes recent advances in eEF1A-targeting anticancer agents, both naturally occurring and synthetically crafted, with regard to their discovery or design, target identification, structure–activity relationship, and mode of action. Their structural diversity and differential eEF1A-targeting mechanisms warrant continuing research in pursuit of curing eEF1A-driven malignancy. |
format | Online Article Text |
id | pubmed-10049629 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100496292023-03-29 Anticancer Small-Molecule Agents Targeting Eukaryotic Elongation Factor 1A: State of the Art Zhang, Han Cai, Jiayou Yu, Siqi Sun, Bin Zhang, Weicheng Int J Mol Sci Review Eukaryotic elongation factor 1A (eEF1A) canonically delivers amino acyl tRNA to the ribosomal A site during the elongation stage of protein biosynthesis. Yet paradoxically, the oncogenic nature of this instrumental protein has long been recognized. Consistently, eEF1A has proven to be targeted by a wide assortment of small molecules with excellent anticancer activity, among which plitidepsin has been granted approval for the treatment of multiple myeloma. Meanwhile, metarrestin is currently under clinical development for metastatic cancers. Bearing these exciting advances in mind, it would be desirable to present a systematic up-to-date account of the title topic, which, to the best of our knowledge, has thus far been unavailable in the literature. The present review summarizes recent advances in eEF1A-targeting anticancer agents, both naturally occurring and synthetically crafted, with regard to their discovery or design, target identification, structure–activity relationship, and mode of action. Their structural diversity and differential eEF1A-targeting mechanisms warrant continuing research in pursuit of curing eEF1A-driven malignancy. MDPI 2023-03-08 /pmc/articles/PMC10049629/ /pubmed/36982256 http://dx.doi.org/10.3390/ijms24065184 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Zhang, Han Cai, Jiayou Yu, Siqi Sun, Bin Zhang, Weicheng Anticancer Small-Molecule Agents Targeting Eukaryotic Elongation Factor 1A: State of the Art |
title | Anticancer Small-Molecule Agents Targeting Eukaryotic Elongation Factor 1A: State of the Art |
title_full | Anticancer Small-Molecule Agents Targeting Eukaryotic Elongation Factor 1A: State of the Art |
title_fullStr | Anticancer Small-Molecule Agents Targeting Eukaryotic Elongation Factor 1A: State of the Art |
title_full_unstemmed | Anticancer Small-Molecule Agents Targeting Eukaryotic Elongation Factor 1A: State of the Art |
title_short | Anticancer Small-Molecule Agents Targeting Eukaryotic Elongation Factor 1A: State of the Art |
title_sort | anticancer small-molecule agents targeting eukaryotic elongation factor 1a: state of the art |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10049629/ https://www.ncbi.nlm.nih.gov/pubmed/36982256 http://dx.doi.org/10.3390/ijms24065184 |
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