2. Academic Validation
  3. Proteolysis-targeting chimeras in biotherapeutics: Current trends and future applications

Proteolysis-targeting chimeras in biotherapeutics: Current trends and future applications

  • Eur J Med Chem. 2023 Sep 5:257:115447. doi: 10.1016/j.ejmech.2023.115447.
Qiong Li 1,  Li Zhou 2,  Siyuan Qin 1,  Zhao Huang 1,  Bowen Li 1,  Ruolan Liu 3,  Mei Yang 1,  Edouard C Nice 4,  Huili Zhu 5,  Canhua Huang 6
Affiliations

Affiliations

  • 1 West China School of Basic Medical Sciences and Forensic Medicine, State Key Laboratory of Biotherapy and Cancer Center, and West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, PR China.
  • 2 Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, PR China.
  • 3 School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China.
  • 4 Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.
  • 5 Department of Reproductive Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital of Sichuan University, Chengdu, 610041, PR China. Electronic address: hlzhu78@139.com.
  • 6 West China School of Basic Medical Sciences and Forensic Medicine, State Key Laboratory of Biotherapy and Cancer Center, and West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, PR China; School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, PR China. Electronic address: hcanhua@scu.edu.cn.
PMID: 37229829 DOI: 10.1016/j.ejmech.2023.115447
Abstract

The success of inhibitor-based therapeutics is largely constrained by the acquisition of therapeutic resistance, which is partially driven by the undruggable proteome. The emergence of proteolysis targeting chimera (PROTAC) technology, designed for degrading proteins involved in specific biological processes, might provide a novel framework for solving the above constraint. A heterobifunctional PROTAC molecule could structurally connect an E3 ubiquitin Ligase ligand with a protein of interest (POI)-binding ligand by chemical linkers. Such technology would result in the degradation of the targeted protein via the ubiquitin-proteasome system (UPS), opening up a novel way of selectively inhibiting undruggable proteins. Herein, we will highlight the advantages of PROTAC technology and summarize the current understanding of the potential mechanisms involved in biotherapeutics, with a particular focus on its application and development where therapeutic benefits over classical small-molecule inhibitors have been achieved. Finally, we discuss how this technology can contribute to developing biotherapeutic drugs, such as antivirals against infectious diseases, for use in clinical practices.

Keywords

Biotherapeutics; Drug development; PROTACs; Protein degradation.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z