Encoding and display technologies for combinatorial libraries in drug discovery:The coming of age from biology to therapy

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外文摘要：Drug discovery is a sophisticated process that incorporates scientific innovations and cutting-edge technologies.Compared to traditional bioactivity-based screening methods,encoding and display technologies for combinatorial libraries have recently advanced from proof-of-principle experiments to promising tools for pharmaceutical hit discovery due to their high screening efficiency,throughput,and resource minimization.This review systematically summarizes the development history,typology,and prospective applications of encoding and displayed technologies,including phage display,ribosomal display,mRNA display,yeast cell display,one-bead one-compound,DNA-encoded,peptide nucleic acid-encoded,and new peptide-encoded technologies,and examples of preclinical and clinical translation.We discuss the progress of novel targeted therapeutic agents,covering a spectrum from small-molecule inhibitors and nonpeptidic macrocycles to linear,monocyclic,and bicyclic peptides,in addition to antibodies.We also address the pending challenges and future prospects of drug discovery,including the size of screening libraries,advantages and disadvantages of the technology,clinical translational potential,and market space.This review is intended to establish a comprehensive high-throughput drug discovery strategy for scientific researchers and clinical drug developers.

外文关键词：

Drug screeningPhage displayDNA-encoded chemical librariesPeptide-encoded chemical librariesClinical drugs

作者：

Yu Fan、Ruibing Feng、Xinya Zhang、Zhen-Liang Wang、Feng Xiong、Shuihua Zhang、Zhang-Feng Zhong、Hua Yu、Qing-Wen Zhang、Zhang Zhang、Yitao Wang、Guodong Li

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作者单位：

Macao Centre for Research and Development in Chinese Medicine,State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Macao SAR 999078,China

State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University,of Macau,Macao SAR 999078,China

Zhuhai UM Science and Technology Research Institute,Zhuhai 519031,China

Geriatric Medicine,First People's Hospital of XinXiang and the Fifth Affiliated Hospital of Xinxiang Medical College,Xinxiang 453100,China

Shenzhen Innovation Center for Small Molecule Drug Discovery Co.,Ltd.,Shenzhen 518000,China

International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development,Ministry of Education(MoE)of People's Republic of China,College of Pharmacy,Jinan University,Guangzhou 510632,China

Department of Pharmacy,Guangzhou Red Cross Hospital,Faculty of Medical Science,Jinan University,Guangzhou 510632,China

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基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaScience and Technology Development Fund,Macau SAR,ChinaScience and Technology Development Fund,Macau SAR,ChinaScience and Technology Development Fund,Macau SAR,ChinaScience and Technology Development Fund,Macau SAR,ChinaScience and Technology Development Fund,Macau SAR,ChinaGuangdong Basic and Applied Basic Research Foundation,ChinaNatural science Foundation of Guangdong Province,ChinaNatural science Foundation of Guangdong Province,ChinaShenzhen-Hong Kong-Macau S&T Program(Category C),ChinaResearch Fund of University of Macau,China

项目编号：

82304698323003170048/2023/ITP20150/2022/A3001/2023/ALC0006/2020/AKP005/2023/SKL2021A15151103382024A15150126592023B1515120023SGDX2020110309420200CPG2024-00038-ICMS

出版年：

2024

DOI：

10.1016/j.apsb.2024.04.006

药学学报(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.14(8)