Fragment-based drug discovery supports drugging 'undruggable' protein-protein interactions

被引：31

作者：

Wang, Zhi-Zheng ^{[1
]}

Shi, Xing-Xing ^{[1
]}

Huang, Guang-Yi ^{[1
]}

Hao, Ge-Fei ^{[1
,2
]}

Yang, Guang-Fu ^{[1
]}

机构：

[1] Cent China Normal Univ, Natl Key Lab Green Pesticide, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China

[2] Guizhou Univ, Ctr R&D Fine Chem, Natl Key Lab Green Pesticide, Key Lab Green Pesticide & Agr BioEngn,Minist Educ, Guiyang 550025, Peoples R China

来源：

TRENDS IN BIOCHEMICAL SCIENCES | 2023年 / 48卷 / 06期

基金：

中国国家自然科学基金;

关键词：

HOT-SPOT ANALYSIS; SMALL MOLECULES; AMG; 510; INHIBITOR; NMR; CHALLENGES; DESIGN; BIOINFORMATICS; LIBRARIES; AFFINITY;

D O I：

10.1016/j.tibs.2023.01.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Protein-protein interactions (PPIs) have important roles in various cellular pro-cesses, but are commonly described as 'undruggable' therapeutic targets due to their large, fiat, featureless interfaces. Fragment-based drug discovery (FBDD) has achieved great success in modulating PPIs, with more than ten compounds in clinical trials. Here, we highlight the progress of FBDD in modulating PPIs for therapeutic development. Targeting hot spots that have essential roles in both fragment binding and PPIs provides a shortcut for the development of PPI modulators via FBDD. We highlight successful cases of cracking the 'undruggable' problems of PPIs using fragment-based approaches. We also introduce new technologies and future trends. Thus, we hope that this review will provide useful guidance for drug discovery targeting PPIs.

引用

页码：539 / 552

页数：14

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