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

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 

机构地区：[1]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 Macao,Macao SAR 999078,China [2]State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macao,Macao SAR 999078,China [3]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 [4]Zhuhai UM Science and Technology Research Institute,Zhuhai 519031,China [5]Department of Pharmacy,Guangzhou Red Cross Hospital,Faculty of Medical Science,Jinan University,Guangzhou 510632,China [6]Geriatric Medicine,First People’s Hospital of XinXiang and the Fifth Affiliated Hospital of Xinxiang Medical College,Xinxiang 453100,China [7]Shenzhen Innovation Center for Small Molecule Drug Discovery Co.,Ltd.,Shenzhen 518000,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第8期3362-3384,共23页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(82304698 and 32300317);Science and Technology Development Fund,Macao SAR(file nos.0048/2023/ITP2,0150/2022/A3,001/2023/ALC,0006/2020/AKP and 005/2023/SKL,China);Guangdong Basic and Applied Basic Research Foundation(grant nos 2021A1515110338,China);Natural Science Foundation of Guangdong Province(2024A1515012659 and 2023B1515120023,China);Shenzhen-Hong Kong-Macao S&T Program(Category C)(SGDX2020110309420200,China);the Research Fund of University of Macao(CPG2024-00038-ICMS,China).

摘　　要：Drug discovery is a sophisticated process that incorporates scientific innovations and cuttingedge 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 acidencoded,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.

关 键 词：Drug screening Phage display DNA-encoded chemical libraries Peptide-encoded chemical libraries Clinical drugs 

分 类 号：R979.1[医药卫生—药品]