Twenty years on: the impact of fragments on drug discovery

被引:653
作者
Erlanson, Daniel A. [1 ]
Fesik, Stephen W. [2 ]
Hubbard, Roderick E. [3 ,4 ]
Jahnke, Wolfgang [5 ]
Jhoti, Harren [6 ]
机构
[1] Carmot Therapeut Inc, 409 Illinois St, San Francisco, CA 94158 USA
[2] Vanderbilt Univ, Sch Med, Dept Biochem, 2215 Garland Ave,607 Light Hall, Nashville, TN 37232 USA
[3] Univ York, York Struct Biol Lab, Dept Chem, York YO10 5DD, N Yorkshire, England
[4] Vernalis Res, Granta Pk, Cambridge CB21 6GB, England
[5] Novartis Inst Biomed Res, Novartis Campus, CH-4002 Basel, Switzerland
[6] Astex Pharmaceut, 436 Cambridge Sci Pk,Milton Rd, Cambridge CB4 0QA, England
关键词
SMALL MOLECULES; LIGAND EFFICIENCY; CHEMICAL SPACE; LEAD DISCOVERY; BINDING-SITES; NMR; INHIBITORS; DESIGN; POTENT; IDENTIFICATION;
D O I
10.1038/nrd.2016.109
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
After 20 years of sometimes quiet growth, fragment-based drug discovery (FBDD) has become mainstream. More than 30 drug candidates derived from fragments have entered the clinic, with two approved and several more in advanced trials. FBDD has been widely applied in both academia and industry, as evidenced by the large number of papers from universities, non-profit research institutions, biotechnology companies and pharmaceutical companies. Moreover, FBDD draws on a diverse range of disciplines, from biochemistry and biophysics to computational and medicinal chemistry. As the promise of FBDD strategies becomes increasingly realized, now is an opportune time to draw lessons and point the way to the future. This Review briefly discusses how to design fragment libraries, how to select screening techniques and how to make the most of information gleaned from them. It also shows how concepts from FBDD have permeated and enhanced drug discovery efforts.
引用
收藏
页码:605 / 619
页数:15
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