Undruggable proteins are a class of proteins that are often characterized by large,complex structures or functions that are diffcult to interfere with using conventional drug design strategies.Targeting such undruggab...Undruggable proteins are a class of proteins that are often characterized by large,complex structures or functions that are diffcult to interfere with using conventional drug design strategies.Targeting such undruggable targets has been considered also a great opportunity for treatment of human diseases and has attracted substantial efforts in the field of medicine.Therefore,in this review,we focus on the recent development of drug discovery targeting"undruggable"proteins and their application in clinic.To make this review well organized,we discuss the design strategies targeting the undruggable proteins,including covalent regulation,allosteric inhibition,protein-protein/DNA interaction inhibition,targeted proteins regulation,nucleic acid-based approach,immunotherapy and others.展开更多
基金The study was supported by the Fundamental Research Funds for the National Natural Science Foundation of China(Nos.82104376,82073998,22177084,and 82104373)the Xinglin Scholar Research Premotion Project of Chengdu University of TCM,the Open Research Fund of Chengdu University of Traditional Chinese Medicine State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China,the Fundamental Research Funds of Science&Technology Department of Sichuan Province(Nos.2022NSFSC0626,2023NSFSC1108)the Postdoctoral Research Project of Sichuan Province.
文摘Undruggable proteins are a class of proteins that are often characterized by large,complex structures or functions that are diffcult to interfere with using conventional drug design strategies.Targeting such undruggable targets has been considered also a great opportunity for treatment of human diseases and has attracted substantial efforts in the field of medicine.Therefore,in this review,we focus on the recent development of drug discovery targeting"undruggable"proteins and their application in clinic.To make this review well organized,we discuss the design strategies targeting the undruggable proteins,including covalent regulation,allosteric inhibition,protein-protein/DNA interaction inhibition,targeted proteins regulation,nucleic acid-based approach,immunotherapy and others.
