Clustering Analysis.

<p>Active compounds were clustered based on structural similarity to identify common chemotypes using LeadScope (Leadscope Hosted Client, Leadscope Inc., Columbus, OH). The results show a diversity of structural clusters, with 22 distinct clusters with more than 5 members. (A) Representative compounds from each of the most prominent 7 clusters are shown. (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090766#pone.0090766.s015" target="_blank">Table S5</a>, Cluster Analysis Compounds with Link for a complete list of the 102 molecules in the 7 clusters, their structures, IC₅₀, and active link to the complete PubChem description). Their common structural scaffolds are highlighted in red. These scaffolds are highly polar, including thiazole, triazole, and hydrozide-based derivatives. Another common structural feature is that these small molecules share a linear molecular shape, which suggests that they might compete with GTP at the active site of the G protein. (B) Inhibition-concentration curves for 7 selected compounds, one from each cluster, together with the IC₅₀ for each compound are shown.