"Function-first" lead discovery: mode of action profiling of natural product libraries using image-based screening.
"Function-first" lead discovery: mode of action profiling of natural product libraries using image-based screening.
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DOI：
10.1016/j.chembiol.2012.12.007
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发表时间：
2013-02-21
影响因子：
--
通讯作者：
Linington RG
中科院分区：
文献类型：
--
作者：
Schulze CJ;Bray WM;Woerhmann MH;Stuart J;Lokey RS;Linington RG
Cytological profiling is a high-content image-based screening technology that provides insight into the mode of action (MOA) for test compounds by directly measuring hundreds of phenotypic cellular features. We have extended this recently reported technology to the mechanistic characterization of unknown natural products libraries for the direct prediction of compound MOAs at the primary screening stage. By analyzing a training set of commercial compounds of known mechanism and comparing these profiles to those obtained from natural product library members, we have successfully annotated extracts based on mode of action, dereplicated known compounds based on biological similarity to the training set, and identified and predicted the MOA of a family of new iron siderophores. Coupled with traditional analytical techniques, cytological profiling provides a new avenue for the creation of ‘function-first’ platforms for natural products discovery.
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