Transforming fragments into candidates: small becomes big in medicinal chemistry

被引：138

作者：

de Kloe, Gerdien E. ^{[1
]}

Bailey, David ^{[2
]}

Leurs, Rob ^{[1
]}

de Esch, Iwan J. P. ^{[1
,2
]}

机构：

[1] Vrije Univ Amsterdam, LACDR, Div Med Chem, Dept Pharmacochem,Fac Exact Sci, NL-1081 HV Amsterdam, Netherlands

[2] IOTA Pharmaceut Ltd, St Johns Innovat Ctr, Cambridge CB4 0WS, England

来源：

DRUG DISCOVERY TODAY | 2009年 / 14卷 / 13-14期

关键词：

X-RAY CRYSTALLOGRAPHY; STRUCTURE-BASED DESIGN; SMALL-MOLECULE INHIBITORS; PROTEIN-KINASE-B; HIV-1; REVERSE-TRANSCRIPTASE; PHOSPHATASE 1B INHIBITOR; DNA GYRASE INHIBITORS; HIGH-AFFINITY LIGANDS; DRUG DISCOVERY; LEAD DISCOVERY;

D O I：

10.1016/j.drudis.2009.03.009

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Fragment-based drug discovery (FBDD) represents a logical and efficient approach to lead discovery and optimisation. It can draw on structural, biophysical and biochemical data, incorporating a wide range of inputs, from precise mode-of-binding information on specific fragments to wider ranging pharmacophoric screening surveys using traditional HTS approaches. It is truly an enabling technology for the imaginative medicinal chemist. In this review, we analyse a representative set of 23 published FBDD studies that describe how low molecular weight fragments are being identified and efficiently transformed into higher molecular weight drug candidates. FBDD is now becoming warmly endorsed by industry as well as academia and the focus on small interacting molecules is making a big scientific impact.

引用

页码：630 / 646

页数：17

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