Revolutionizing Drug Targeting Strategies: Integrating Artificial Intelligence and Structure-Based Methods in PROTAC Development
PROteolysis TArgeting Chimera (PROTAC) is an emerging technology in chemical biology and drug discovery. This technique facilitates the complete removal of the target proteins that are “undruggable” or challenging to target through chemical molecules via the Ubiquitin–Proteasome System (UPS). PROTAC...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/12/1649 |
| _version_ | 1827573877216116736 |
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| author | Danishuddin Mohammad Sarwar Jamal Kyoung-Seob Song Keun-Woo Lee Jong-Joo Kim Yeong-Min Park |
| author_facet | Danishuddin Mohammad Sarwar Jamal Kyoung-Seob Song Keun-Woo Lee Jong-Joo Kim Yeong-Min Park |
| author_sort | Danishuddin |
| collection | DOAJ |
| description | PROteolysis TArgeting Chimera (PROTAC) is an emerging technology in chemical biology and drug discovery. This technique facilitates the complete removal of the target proteins that are “undruggable” or challenging to target through chemical molecules via the Ubiquitin–Proteasome System (UPS). PROTACs have been widely explored and outperformed not only in cancer but also in other diseases. During the past few decades, several academic institutes and pharma companies have poured more efforts into PROTAC-related technologies, setting the stage for several major degrader trial readouts in clinical phases. Despite their promising results, the formation of robust ternary orientation, off-target activity, poor permeability, and binding affinity are some of the limitations that hinder their development. Recent advancements in computational technologies have facilitated progress in the development of PROTACs. Researchers have been able to utilize these technologies to explore a wider range of E3 ligases and optimize linkers, thereby gaining a better understanding of the effectiveness and safety of PROTACs in clinical settings. In this review, we briefly explore the computational strategies reported to date for the formation of PROTAC components and discuss the key challenges and opportunities for further research in this area. |
| first_indexed | 2024-03-08T20:27:27Z |
| format | Article |
| id | doaj.art-d20ee12cf42c42189867c1966e602dff |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-08T20:27:27Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-d20ee12cf42c42189867c1966e602dff2023-12-22T14:31:18ZengMDPI AGPharmaceuticals1424-82472023-11-011612164910.3390/ph16121649Revolutionizing Drug Targeting Strategies: Integrating Artificial Intelligence and Structure-Based Methods in PROTAC DevelopmentDanishuddin0Mohammad Sarwar Jamal1Kyoung-Seob Song2Keun-Woo Lee3Jong-Joo Kim4Yeong-Min Park5Department of Biotechnology, Yeungnam University, Gyeongsan 38541, Republic of KoreaBioWiz Laboratories, Inc., Ste-466440 Burroughs St., Detroit, MI 48202, USADepartment of Medical Science, Kosin University College of Medicine, 194 Wachi-ro, Yeongdo-gu, Busan 49104, Republic of KoreaDivision of Life Science, Department of Bio & Medical Big-Data (BK4 Program), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju 52828, Republic of KoreaDepartment of Biotechnology, Yeungnam University, Gyeongsan 38541, Republic of KoreaDepartment of Integrative Biological Sciences and Industry, Sejong University, 209, Neugdong-ro, Gwangjin-gu, Seoul 05006, Republic of KoreaPROteolysis TArgeting Chimera (PROTAC) is an emerging technology in chemical biology and drug discovery. This technique facilitates the complete removal of the target proteins that are “undruggable” or challenging to target through chemical molecules via the Ubiquitin–Proteasome System (UPS). PROTACs have been widely explored and outperformed not only in cancer but also in other diseases. During the past few decades, several academic institutes and pharma companies have poured more efforts into PROTAC-related technologies, setting the stage for several major degrader trial readouts in clinical phases. Despite their promising results, the formation of robust ternary orientation, off-target activity, poor permeability, and binding affinity are some of the limitations that hinder their development. Recent advancements in computational technologies have facilitated progress in the development of PROTACs. Researchers have been able to utilize these technologies to explore a wider range of E3 ligases and optimize linkers, thereby gaining a better understanding of the effectiveness and safety of PROTACs in clinical settings. In this review, we briefly explore the computational strategies reported to date for the formation of PROTAC components and discuss the key challenges and opportunities for further research in this area.https://www.mdpi.com/1424-8247/16/12/1649PROTACsE3 ligaseslinkerartificial intelligence |
| spellingShingle | Danishuddin Mohammad Sarwar Jamal Kyoung-Seob Song Keun-Woo Lee Jong-Joo Kim Yeong-Min Park Revolutionizing Drug Targeting Strategies: Integrating Artificial Intelligence and Structure-Based Methods in PROTAC Development Pharmaceuticals PROTACs E3 ligases linker artificial intelligence |
| title | Revolutionizing Drug Targeting Strategies: Integrating Artificial Intelligence and Structure-Based Methods in PROTAC Development |
| title_full | Revolutionizing Drug Targeting Strategies: Integrating Artificial Intelligence and Structure-Based Methods in PROTAC Development |
| title_fullStr | Revolutionizing Drug Targeting Strategies: Integrating Artificial Intelligence and Structure-Based Methods in PROTAC Development |
| title_full_unstemmed | Revolutionizing Drug Targeting Strategies: Integrating Artificial Intelligence and Structure-Based Methods in PROTAC Development |
| title_short | Revolutionizing Drug Targeting Strategies: Integrating Artificial Intelligence and Structure-Based Methods in PROTAC Development |
| title_sort | revolutionizing drug targeting strategies integrating artificial intelligence and structure based methods in protac development |
| topic | PROTACs E3 ligases linker artificial intelligence |
| url | https://www.mdpi.com/1424-8247/16/12/1649 |
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