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利用药效团导向虚拟筛选鉴定新型丙型肝炎病毒RNA依赖性RNA聚合酶抑制剂

Identification of novel HCV RNA-dependent RNA polymerase inhibitors using pharmacophore-guided virtual screening.

作者信息

Kim Jinyoung, Kim Ki-sun, Kim Dong-Eun, Chong Youhoon

机构信息

Department of Bioscience and Biotechnology, Konkuk University, Seoul, Korea.

出版信息

Chem Biol Drug Des. 2008 Dec;72(6):585-91. doi: 10.1111/j.1747-0285.2008.00730.x.

DOI:10.1111/j.1747-0285.2008.00730.x
PMID:19090925
Abstract

We performed pharmacophore-guided virtual screening experiments using FlexX-Pharm to identify novel inhibitors of hepatitis C virus RNA-dependent RNA polymerase. Pharmacophore model generated from our previous analysis of the binding modes as well as structure-based three-dimensional quantitative structure-activity relationship studies of aryl diketoacid analogues was used. In pharmacophore-guided virtual screening study, among 37 447 compounds in LeadQuest chemical library, 40 compounds were selected as novel candidates of hepatitis C virus RNA-dependent RNA polymerase inhibitors, and their biological activities were evaluated. Especially, T29 was chosen for further development.

摘要

我们使用FlexX-Pharm进行了药效团导向的虚拟筛选实验，以鉴定丙型肝炎病毒RNA依赖性RNA聚合酶的新型抑制剂。使用了从我们之前对结合模式的分析以及芳基二酮酸类似物的基于结构的三维定量构效关系研究中生成的药效团模型。在药效团导向的虚拟筛选研究中，在LeadQuest化学库的37447种化合物中，选择了40种化合物作为丙型肝炎病毒RNA依赖性RNA聚合酶抑制剂的新型候选物，并对其生物活性进行了评估。特别是，选择了T29进行进一步开发。

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