Discovering Potent Small Molecule Inhibitors of Cyclophilin A Using de Novo Drug Design Approach

详细信息    查看全文

• 作者：Shuaishuai Ni ; Yaxia Yuan ; Jin Huang ; Xiaona Mao ; Maosheng Lv ; Jin Zhu ; Xu Shen ; Jianfeng Pei ; Luhua Lai ; Hualiang Jiang ; Jian Li
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：September 10, 2009
• 年：2009
• 卷：52
• 期：17
• 页码：5295-5298
• 全文大小：742K
• 年卷期：v.52,no.17(September 10, 2009)
• ISSN：1520-4804

文摘

This work describes an integrated approach of de novo drug design, chemical synthesis, and bioassay for quick identification of a series of novel small molecule cyclophilin A (CypA) inhibitors (1−3). The activities of the two most potent CypA inhibitors (3h and 3i) are 2.59 and 1.52 nM, respectively, which are about 16 and 27 times more potent than that of cyclosporin A. This study clearly demonstrates the power of our de novo drug design strategy and the related program LigBuilder 2.0 in drug discovery.