Ren Jing, Li Jian, Shi Feng, Wang Xin, He Jian-Hua, Xu Ye-Chun, Zhang Nai-Xia, Xiong Bing, Shen Jing-Kang
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Yao Xue Xue Bao. 2013 Jan;48(1):14-24.
As an extension of the structure-based drug discovery, fragment-based drug discovery is matured increasingly, and plays an important role in drug development. Fragments in a small library, with lower molecular mass and high "ligand efficiency", are detected by SPR, MS, NMR, X-ray crystallography technologies and other biophysical methods. Then they are considered as starting points for chemical optimization with the guidance of structural biology methods to get good "drug-like" lead and candidate compounds. In this article, we reviewed the current progress of fragment-based drug discovery and detailed a number of examples to illustrate the novel strategies.
作为基于结构的药物发现的延伸,基于片段的药物发现日益成熟,并在药物开发中发挥着重要作用。通过表面等离子体共振(SPR)、质谱(MS)、核磁共振(NMR)、X射线晶体学技术及其他生物物理方法,从小型文库中检测出分子量较低且具有高“配体效率”的片段。然后,在结构生物学方法的指导下,将这些片段作为化学优化的起点,以获得具有良好“类药”性质的先导化合物和候选化合物。在本文中,我们综述了基于片段的药物发现的当前进展,并详细列举了一些实例以说明这些新策略。