Concepts and Core Principles of Fragment-Based Drug Design

被引：139

作者：

Kirsch, Philine ^{[1
,2
]}

Hartman, Alwin M. ^{[1
,3
]}

Hirsch, Anna K. H. ^{[1
,3
]}

Empting, Martin ^{[1
,2
]}

机构：

[1] Helmholtz Ctr Infect Res HZI, Helmholtz Inst Pharmaceut Res Saarland HIPS, Dept Drug Design & Optimizat DDOP, Campus E8-1, D-66123 Saarbrucken, Germany

[2] Saarland Univ, Dept Pharm, Campus E8-1, D-66123 Saarbrucken, Germany

[3] Univ Groningen, Stratingh Inst Chem, Nijenborgh 7, NL-9747 AG Groningen, Netherlands

来源：

MOLECULES | 2019年 / 24卷 / 23期

关键词：

fragment-based drug design; biophysical screening; rule-of-three; ligand efficiency; fragment optimization; DIFFERENTIAL SCANNING FLUOROMETRY; DYNAMIC COMBINATORIAL CHEMISTRY; SURFACE-PLASMON RESONANCE; THERMAL SHIFT ASSAYS; MICROSCALE THERMOPHORESIS; HIGH-THROUGHPUT; PSEUDOMONAS-AERUGINOSA; LIGAND INTERACTIONS; HIT IDENTIFICATION; CHEMICAL SPACE;

D O I：

10.3390/molecules24234309

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：

In this review, a general introduction to fragment-based drug design and the underlying concepts is given. General considerations and methodologies ranging from library selection/construction over biophysical screening and evaluation methods to in-depth hit qualification and subsequent optimization strategies are discussed. These principles can be generally applied to most classes of drug targets. The examples given for fragment growing, merging, and linking strategies at the end of the review are set in the fields of enzyme-inhibitor design and macromolecule-macromolecule interaction inhibition. Building upon the foundation of fragment-based drug discovery (FBDD) and its methodologies, we also highlight a few new trends in FBDD.

引用

页数：22

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