Issues

The structure of NVP-BEZ235 alone (top) or docked in the catalytic site of PI3Kα (bottom). The model was generated using the coordinates of known PI3Kγ crystal structures. All possible orientations were considered to determine which one was the most consistent with the available structure-activity relationship, in particular with regard to the importance of the hydrogen bond acceptor nitrogen atoms present in the chemical structure of the inhibitor for high potency. For details, see Maira et al., in this issue.