Rosén Josefin, Gottfries Johan, Muresan Sorel, Backlund Anders, Oprea Tudor I
Department of Medicinal Chemistry, Division of Pharmacognosy, BMC, Uppsala University, Uppsala, Sweden.
J Med Chem. 2009 Apr 9;52(7):1953-62. doi: 10.1021/jm801514w.
Natural products (NPs) are a rich source of novel compound classes and new drugs. In the present study we have used the chemical space navigation tool ChemGPS-NP to evaluate the chemical space occupancy by NPs and bioactive medicinal chemistry compounds from the database WOMBAT. The two sets differ notably in coverage of chemical space, and tangible leadlike NPs were found to cover regions of chemical space that lack representation in WOMBAT. Property based similarity calculations were performed to identify NP neighbors of approved drugs. Several of the NPs revealed by this method were confirmed to exhibit the same activity as their drug neighbors. The identification of leads from a NP starting point may prove a useful strategy for drug discovery in the search for novel leads with unique properties.
天然产物(NPs)是新型化合物类别和新药的丰富来源。在本研究中,我们使用了化学空间导航工具ChemGPS-NP来评估天然产物以及来自WOMBAT数据库的生物活性药物化学化合物在化学空间中的占有率。这两组在化学空间覆盖方面存在显著差异,并且发现具有切实可行的类先导物特征的天然产物覆盖了WOMBAT中未涵盖的化学空间区域。进行了基于性质的相似性计算以识别已批准药物的天然产物类似物。通过该方法揭示的几种天然产物被证实与其药物类似物表现出相同的活性。从天然产物出发来识别先导物可能是药物发现中寻找具有独特性质的新型先导物的一种有用策略。