Figure 3. Substructure similarity range of Cgr2 enzyme susceptible compounds.

Substructure based clustering distinguishes experimentally characterized substrates from non-substrates of the Cgr2 enzyme. Digoxin clusters with other cardenolides that are experimentally characterized substrates (Koppel et al., 2018) for Cgr2 at substructure similarity values greater than 0.8. Compounds that are not substrates of Cgr2 have lower substructure similarity with digoxin; compounds with minimal reduction (Koppel et al., 2018) include progesterone and cortisone (substructure similarity <= 0.63). Color bar intensity increases with compound overlap with digoxin.