Fragment-based drug discovery
10.3321/j.issn:1000-5048.2009.04.001
- VernacularTitle:基于分子片段的药物发现
- Author:
Xiaojian WANG
;
Qian YANG
;
Qidong YOU
- Publication Type:Journal Article
- Keywords:
fragments;
pharmacophore;
molecular framework;
new drug research;
drug discovery
- From:
Journal of China Pharmaceutical University
2009;40(4):289-296
- CountryChina
- Language:Chinese
-
Abstract:
A drug is composed of fragments with their functional and structural characteristics. Functional fragments contain structural elements known as pharmacophores which generate the bioactivity of the drugs, while structural fragments assemble the functional fragments into a specific skeleton also crucial for the activity. Although drug molecules possess structural diversity and complexity, the fragments usually have some similarity. They normally have simple texture, low molecular weight and log P. The aim of fragment-based drug discovery is to classify and screen the collections of fragments and subsequently expand, link, or merge them to obtain new chemical entities. This theory refines the traditional structure-based and the high throughput screen-based drug discovery strategy, and facilitates the reduction of molecular size and the improvement of drug-like properties, which will certainly increase the probability of developing new drugs. In this article, we reviewed the concept, methodology of fragment-based drug discovery and detailed a number of examples to illustrate the optimization strategies of this discovery method.
