首页|Targeting the undruggables-the power of protein degraders
Targeting the undruggables-the power of protein degraders
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Undruggable targets typically refer to a class of therapeutic targets that are difficult to target through conventional methods or have not yet been targeted,but are of great clinical significance.According to statistics,over 80％of disease-related pathogenic proteins cannot be targeted by current conventional treatment methods.In recent years,with the advancement of basic research and new technologies,the development of various new technologies and mechanisms has brought new perspectives to overcome challenging drug targets.Among them,targeted protein degradation technology is a breakthrough drug development strategy for challenging drug targets.This technology can specifically identify target pro-teins and directly degrade pathogenic target proteins by utilizing the inherent protein degradation path-ways within cells.This new form of drug development includes various types such as proteolysis targeting chimera(PROTAC),molecular glue,lysosome-targeting Chimaera(LYTAC),autophagosome-tethering compound(ATTEC),autophagy-targeting chimera(AUTAC),autophagy-targeting chimera(AUTOTAC),degrader-antibody conjugate(DAC).This article systematically summarizes the application of targeted protein degradation technology in the development of degraders for challenging drug targets.Finally,the article looks forward to the future development direction and application prospects of tar-geted protein degradation technology.
UndruggablesTargeted protein degradationPROTACMolecule glueDACLYTAC
State Key Laboratory of Molecular Oncology,MOE Key Laboratory of Protein Sciences,MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology,School of Pharmaceutical Sciences,Tsinghua University,Beijing 100084,China
School of Pharmacy,Second Military Medical University,Shanghai 200433,China
State Key Laboratory of Chemical Biology,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032,China
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National Key R&D Program of ChinaNational Key R&D Program of ChinaNational Key R&D Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of China
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