Design, Synthesis, and Biological Evaluation of Proteolysis Targeting Chimeras (PROTACs) for the Dual Degradation of IGF-1R and Src

A focused PROTAC library was developed to degrade both IGF-1R and Src proteins, which are associated with various cancers. PROTACs with IGF-1R and Src degradation potentials were synthesized by tethering different inhibitor warhead units and the E3 ligase (CRBN) recruiting-pomalidomide with various...

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Autores principales: Manda, Sudhakar, Lee, Na Keum, Oh, Dong-Chan, Lee, Jeeyeon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221895/
https://www.ncbi.nlm.nih.gov/pubmed/32340152
http://dx.doi.org/10.3390/molecules25081948
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author Manda, Sudhakar
Lee, Na Keum
Oh, Dong-Chan
Lee, Jeeyeon
author_facet Manda, Sudhakar
Lee, Na Keum
Oh, Dong-Chan
Lee, Jeeyeon
author_sort Manda, Sudhakar
collection PubMed
description A focused PROTAC library was developed to degrade both IGF-1R and Src proteins, which are associated with various cancers. PROTACs with IGF-1R and Src degradation potentials were synthesized by tethering different inhibitor warhead units and the E3 ligase (CRBN) recruiting-pomalidomide with various linkers. The designed PROTACs 12a–b inhibited the proliferation and migration of MCF7 and A549 cancer cells with low micromolar potency (1–5 μM) in various cellular assays.
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spelling pubmed-72218952020-05-22 Design, Synthesis, and Biological Evaluation of Proteolysis Targeting Chimeras (PROTACs) for the Dual Degradation of IGF-1R and Src Manda, Sudhakar Lee, Na Keum Oh, Dong-Chan Lee, Jeeyeon Molecules Article A focused PROTAC library was developed to degrade both IGF-1R and Src proteins, which are associated with various cancers. PROTACs with IGF-1R and Src degradation potentials were synthesized by tethering different inhibitor warhead units and the E3 ligase (CRBN) recruiting-pomalidomide with various linkers. The designed PROTACs 12a–b inhibited the proliferation and migration of MCF7 and A549 cancer cells with low micromolar potency (1–5 μM) in various cellular assays. MDPI 2020-04-23 /pmc/articles/PMC7221895/ /pubmed/32340152 http://dx.doi.org/10.3390/molecules25081948 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Manda, Sudhakar
Lee, Na Keum
Oh, Dong-Chan
Lee, Jeeyeon
Design, Synthesis, and Biological Evaluation of Proteolysis Targeting Chimeras (PROTACs) for the Dual Degradation of IGF-1R and Src
title Design, Synthesis, and Biological Evaluation of Proteolysis Targeting Chimeras (PROTACs) for the Dual Degradation of IGF-1R and Src
title_full Design, Synthesis, and Biological Evaluation of Proteolysis Targeting Chimeras (PROTACs) for the Dual Degradation of IGF-1R and Src
title_fullStr Design, Synthesis, and Biological Evaluation of Proteolysis Targeting Chimeras (PROTACs) for the Dual Degradation of IGF-1R and Src
title_full_unstemmed Design, Synthesis, and Biological Evaluation of Proteolysis Targeting Chimeras (PROTACs) for the Dual Degradation of IGF-1R and Src
title_short Design, Synthesis, and Biological Evaluation of Proteolysis Targeting Chimeras (PROTACs) for the Dual Degradation of IGF-1R and Src
title_sort design, synthesis, and biological evaluation of proteolysis targeting chimeras (protacs) for the dual degradation of igf-1r and src
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221895/
https://www.ncbi.nlm.nih.gov/pubmed/32340152
http://dx.doi.org/10.3390/molecules25081948
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