Fig. 2: Screens to identify inhibitors of RQ-dependent metabolism.
From: Identification of a family of species-selective complex I inhibitors as potential anthelmintics
a Overview of the screening strategy for RIKEN Pilot library. The Pilot library consists of 400 compounds, each representative of a cluster of related molecules and analogs from a diverse collection of ~25,000 natural products and derivatives. The initial 400 molecules were screened in two assays of C. elegans viability. Analogs, derivatives, and related molecules within the same structural cluster of each hit molecule were provided for additional screening—expanding individual hits into structural groups. Structural groups of molecules were tested in secondary assays to identify group members with the greatest bioactivity and/or selectivity. b RIKEN libraries of natural products (Authentic and Pilot) were screened at 50 µM in triplicate in two assays of C. elegans viability: KCN survival assay and liquid development/viability (see Methods). Each dot represents a single NPD and is the mean of three biological replicates in each respective assay. Data are presented as modified z-scores, calculated using the median and median absolute deviation (MAD) of each chemical plate. 8 NPDs were identified as hits in the KCN survival assay alone; 9 NPDs were identified as hits in the development and viability assay alone; and 2 NPDs were identified as hits in both assays (z-score < −3).
