文章基本信息

标题：Repurposing of FDA approved ring systems through bi-directional target-ring system dual screening
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作者：Surendra Kumar ; Cheongyun Jang ; Lalita Subedi 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2020
卷号：10
期号：1
页码：1-14
DOI：10.1038/s41598-020-78077-9
出版社：Springer Nature
摘要：In drug repurposing approaches, the chemically diverse and potentially safe molecules can be explored as therapeutic potential beyond those originally targeted indications. However, accessible information on a limited number of drug pipelines can lead to competitive over-heating issues, and intellectual property rights also restrict the free investigation in chemical space. As a complementary approach to the drawbacks, ring systems of approved drugs (instead of clinical drugs) can be optimized and used for repurposing purposes. In this study, bi-directional target (T) and ring system (R) dual screening (TR screening) was developed for the repurposing of their rarely used ring systems from FDA approved drugs. The TR screening suggested RAR β and cyproheptadine as the best pair of target and ring system to escape a saddle point. The selected ring system was virtually grown and elaborated with the defined criteria: synthesizability, drug-likeness, and docking pose showing the top scores. The achieved compounds were synthesized and biologically tested with an acceptable ADME/T profile.
其他摘要：Abstract In drug repurposing approaches, the chemically diverse and potentially safe molecules can be explored as therapeutic potential beyond those originally targeted indications. However, accessible information on a limited number of drug pipelines can lead to competitive over-heating issues, and intellectual property rights also restrict the free investigation in chemical space. As a complementary approach to the drawbacks, ring systems of approved drugs (instead of clinical drugs) can be optimized and used for repurposing purposes. In this study, bi-directional target (T) and ring system (R) dual screening (TR screening) was developed for the repurposing of their rarely used ring systems from FDA approved drugs. The TR screening suggested RAR β and cyproheptadine as the best pair of target and ring system to escape a saddle point. The selected ring system was virtually grown and elaborated with the defined criteria: synthesizability, drug-likeness, and docking pose showing the top scores. The achieved compounds were synthesized and biologically tested with an acceptable ADME/T profile.