Figure 7

A 2D similarity method can sometimes correctly predict a target. Shown above are the 2D structures and 3D similarity overlays for the drug promethazine (a histamine H1 receptor antagonist) compared to two dopamine receptor antagonists, promazine and trifluoperazine. Although promethazine is prescribed as an antihistamine (Phenergan), it is a branched derivative of the antipsychotic phenothiazines and is known to have about 1/10^th the dopamine receptor antagonistic activity. Our 2D method alone was sufficient to identify the dopamine receptors as an off-target of promethazine. As shown above, the Log Odds predictions that promethazine is a dopamine D2 receptor ligand were 2D = 10, 3D = 15, and the combination of 2D and 3D = 22. Note that at a log-odds score of 10, just 20% of secondary targets are identified by 2D alone, with 50% and 60% identified by 3D and the combination of 2D+3D, respectively.