REVIEW ARTICLE
Strategies for designing proteolysis targeting chimaeras (PROTACs)
Shipeng He,
Guoqiang Dong,
Junfei Cheng,
Ying Wu,
Chunquan Sheng,
Shipeng He
Institute of Translational Medicine, Shanghai University, Shanghai, China
Search for more papers by this authorGuoqiang Dong
School of Pharmacy, Second Military Medical University, Shanghai, China
Search for more papers by this authorJunfei Cheng
School of Pharmacy, Second Military Medical University, Shanghai, China
Search for more papers by this authorYing Wu
School of Pharmacy, Second Military Medical University, Shanghai, China
Department of Pharmacy, 920th Hospital of Joint Logistics Support Force, Kunming, China
Search for more papers by this authorCorresponding Author
Chunquan Sheng
School of Pharmacy, Second Military Medical University, Shanghai, China
Correspondence Chunquan Sheng, School of Pharmacy, Second Military Medical University, 325 Guohe Rd, Shanghai 200433, China.
Email: [email protected]
Search for more papers by this authorShipeng He,
Guoqiang Dong,
Junfei Cheng,
Ying Wu,
Chunquan Sheng,
Shipeng He
Institute of Translational Medicine, Shanghai University, Shanghai, China
Search for more papers by this authorGuoqiang Dong
School of Pharmacy, Second Military Medical University, Shanghai, China
Search for more papers by this authorJunfei Cheng
School of Pharmacy, Second Military Medical University, Shanghai, China
Search for more papers by this authorYing Wu
School of Pharmacy, Second Military Medical University, Shanghai, China
Department of Pharmacy, 920th Hospital of Joint Logistics Support Force, Kunming, China
Search for more papers by this authorCorresponding Author
Chunquan Sheng
School of Pharmacy, Second Military Medical University, Shanghai, China
Correspondence Chunquan Sheng, School of Pharmacy, Second Military Medical University, 325 Guohe Rd, Shanghai 200433, China.
Email: [email protected]
Search for more papers by this authorShipeng He, Guoqiang Dong, Junfei Cheng, and Ying Wu contributed equally to this study.
Abstract
Proteolysis targeting chimaeras (PROTACs) is a cutting edge and rapidly growing technique for new drug discovery and development. Currently, the largest challenge in the molecular design and drug development of PROTACs is efficient identification of potent and drug-like degraders. This review aims to comprehensively summarize and analyse state-of-the-art methods and strategies in the design of PROTACs. We provide a detailed illustration of the general principles and tactics for designing potent PROTACs, highlight representative case studies, and discuss the advantages and limitations of these strategies. Particularly, structure-based rational PROTAC design and emerging new types of PROTACs (e.g., homo-PROTACs, multitargeting PROTACs, photo-control PROTACs and PROTAC-based conjugates) will be focused on.
CONFLICT OF INTERESTS
The authors declare that there are no conflict of interests.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon request.
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