Emerging Strategies in Proteolysis-Targeting Chimeras (PROTACs): Highlights from 2022
Targeted protein degradation (TPD) is a promising therapeutic modality that has garnered attention in academic, industrial, and pharmaceutical research for treating diseases such as cancer, neurodegenerative disorders, inflammation, and viral infections. In this context, proteolysis-targeting chimer...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5190 |
| _version_ | 1797611328380076032 |
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| author | Rekha Tamatam Dongyun Shin |
| author_facet | Rekha Tamatam Dongyun Shin |
| author_sort | Rekha Tamatam |
| collection | DOAJ |
| description | Targeted protein degradation (TPD) is a promising therapeutic modality that has garnered attention in academic, industrial, and pharmaceutical research for treating diseases such as cancer, neurodegenerative disorders, inflammation, and viral infections. In this context, proteolysis-targeting chimeras (PROTACs) present a reliable technology for degrading disease-causing proteins. PROTACs complement small-molecule inhibitors, which primarily rely on direct protein regulation. From concept-to-clinic, PROTACs have evolved from cell impermeable peptide molecules to orally bioavailable drugs. Despite their potential in medicinal chemistry, certain aspects regarding PROTACs remain unclear. The clinical significance of PROTACs is primarily limited owing to their lack of selectivity and drug-like properties. This review focused on recently reported PROTAC strategies, particularly in 2022. It aimed to address and overcome the challenges posed by classical PROTACs by correlating them with emerging approaches with improved selectivity and controllability, cell permeability, linker flexibility, druggability, and PROTAC-based approaches, developed in 2022. Furthermore, recently reported PROTAC-based approaches are discussed, highlighting each of their advantages and limitations. We predict that several improved PROTAC molecules will be accessible for treating patients exhibiting various conditions, including cancer, neurodegenerative disorders, inflammation, and viral infections. |
| first_indexed | 2024-03-11T06:27:20Z |
| format | Article |
| id | doaj.art-ae90745684f54dfab8a33aa24163f359 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:27:20Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ae90745684f54dfab8a33aa24163f3592023-11-17T11:30:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246519010.3390/ijms24065190Emerging Strategies in Proteolysis-Targeting Chimeras (PROTACs): Highlights from 2022Rekha Tamatam0Dongyun Shin1College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Republic of KoreaCollege of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Republic of KoreaTargeted protein degradation (TPD) is a promising therapeutic modality that has garnered attention in academic, industrial, and pharmaceutical research for treating diseases such as cancer, neurodegenerative disorders, inflammation, and viral infections. In this context, proteolysis-targeting chimeras (PROTACs) present a reliable technology for degrading disease-causing proteins. PROTACs complement small-molecule inhibitors, which primarily rely on direct protein regulation. From concept-to-clinic, PROTACs have evolved from cell impermeable peptide molecules to orally bioavailable drugs. Despite their potential in medicinal chemistry, certain aspects regarding PROTACs remain unclear. The clinical significance of PROTACs is primarily limited owing to their lack of selectivity and drug-like properties. This review focused on recently reported PROTAC strategies, particularly in 2022. It aimed to address and overcome the challenges posed by classical PROTACs by correlating them with emerging approaches with improved selectivity and controllability, cell permeability, linker flexibility, druggability, and PROTAC-based approaches, developed in 2022. Furthermore, recently reported PROTAC-based approaches are discussed, highlighting each of their advantages and limitations. We predict that several improved PROTAC molecules will be accessible for treating patients exhibiting various conditions, including cancer, neurodegenerative disorders, inflammation, and viral infections.https://www.mdpi.com/1422-0067/24/6/5190targeted protein degradationproteolysis-targeting chimerasselectivitypermeabilitylinker flexibility |
| spellingShingle | Rekha Tamatam Dongyun Shin Emerging Strategies in Proteolysis-Targeting Chimeras (PROTACs): Highlights from 2022 International Journal of Molecular Sciences targeted protein degradation proteolysis-targeting chimeras selectivity permeability linker flexibility |
| title | Emerging Strategies in Proteolysis-Targeting Chimeras (PROTACs): Highlights from 2022 |
| title_full | Emerging Strategies in Proteolysis-Targeting Chimeras (PROTACs): Highlights from 2022 |
| title_fullStr | Emerging Strategies in Proteolysis-Targeting Chimeras (PROTACs): Highlights from 2022 |
| title_full_unstemmed | Emerging Strategies in Proteolysis-Targeting Chimeras (PROTACs): Highlights from 2022 |
| title_short | Emerging Strategies in Proteolysis-Targeting Chimeras (PROTACs): Highlights from 2022 |
| title_sort | emerging strategies in proteolysis targeting chimeras protacs highlights from 2022 |
| topic | targeted protein degradation proteolysis-targeting chimeras selectivity permeability linker flexibility |
| url | https://www.mdpi.com/1422-0067/24/6/5190 |
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