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Network pharmacology: the next paradigm in drug discovery

hh1985 添加于 2009-12-7 02:51 | 1493 次阅读 | 0 个评论

作者
Hopkins AL
摘要
The dominant paradigm in drug discovery is the concept of designing maximally selective ligands to act on individual drug targets. However, many effective drugs act via modulation of multiple proteins rather than single targets. Advances in systems biology are revealing a phenotypic robustness and a network structure that strongly suggests that exquisitely selective compounds, compared with multitarget drugs, may exhibit lower than desired clinical efficacy. This new appreciation of the role of polypharmacology has significant implications for tackling the two major sources of attrition in drug development—efficacy and toxicity. Integrating network biology and polypharmacology holds the promise of expanding the current opportunity space for druggable targets. However, the rational design of polypharmacology faces considerable challenges in the need for new methods to validate target combinations and optimize multiple structure-activity relationships while maintaining drug-like properties. Advances in these areas are creating the foundation of the next paradigm in drug discovery: network pharmacology.
详细资料
- 文献种类:期刊
- 期刊名称: Nature Chemical Biology
- 期刊缩写: Nat Chem Biol
- 期卷页: 2008年第4卷第11期 682-690页
- ISBN: 1552-4450
标签

polypharmacology drug discovery network biology protein interaction
相关链接 DOI URL
附件
Network pharmacology: the next paradigm in drug discovery