From PROTAC to TPD: Advances and Opportunities in Targeted Protein Degradation

Author:

Wang Siqi1ORCID,He Fuchu12,Tian Chunyan1ORCID,Sun Aihua12

Affiliation:

1. State Key Laboratory of Medical Proteomics, National Center for Protein Sciences (Beijing), Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing 102206, China

2. Research Unit of Proteomics Dirven Cancer Precision Medicine, Chinese Academy of Medical Sciences, Beijing 100050, China

Abstract

PROTAC is a rapidly developing engineering technology for targeted protein degradation using the ubiquitin–proteasome system, which has promising applications for inflammatory diseases, neurodegenerative diseases, and malignant tumors. This paper gives a brief overview of the development and design principles of PROTAC, with a special focus on PROTAC-based explorations in recent years aimed at achieving controlled protein degradation and improving the bioavailability of PROTAC, as well as TPD technologies that use other pathways such as autophagy and lysosomes to achieve targeted protein degradation.

Funder

National Key R&D Program of China

National Natural Science Foundation of China

National Science Foundation for Young Scientists of China

Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences

The Specific Research Fund for TCM Science and Technology of Guangdong Provincial Hospital of Chinese Medicine

Publisher

MDPI AG

Subject

Drug Discovery,Pharmaceutical Science,Molecular Medicine

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