Fragment-Based Approaches in Drug Discovery and Chemical Biology
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- 作者：Duncan E. Scott ; Anthony G. Coyne ; Sean A. Hudson ; Chris Abell
- 刊名：Biochemistry
- 出版年：2012
- 出版时间：June 26, 2012
- 年：2012
- 卷：51
- 期：25
- 页码：4990-5003
- 全文大小：615K
- 年卷期：v.51,no.25(June 26, 2012)
- ISSN：1520-4995
文摘
Fragment-based approaches to finding novel small molecules that bind to proteins are now firmly established in drug discovery and chemical biology. Initially developed primarily in a few centers in the biotech and pharma industry, this methodology has now been adopted widely in both the pharmaceutical industry and academia. After the initial success with kinase targets, the versatility of this approach has now expanded to a broad range of different protein classes. Herein we describe recent fragment-based approaches to a wide range of target types, including Hsp90, 尾-secretase, and allosteric sites in human immunodeficiency virus protease and fanesyl pyrophosphate synthase. The role of fragment-based approaches in an academic research environment is also examined with an emphasis on neglected diseases such as tuberculosis. The development of a fragment library, the fragment screening process, and the subsequent fragment hit elaboration will be discussed using examples from the literature.