Fig. 8. Molecular basis for the selective CYP3A4 inhibition by SCM-1 analogs.

a SCM-1 analogs bind preferentially to the mostly hydrophobic surface 1 of CYP3A4 when region A groups (indicated as R in red) are hydrophobic of limited size. b Due to a wall created by the C-terminal loop in CYP3A5, SCM-1 analogs are forced to interact with the alternative surface 2, but the highly polar environment discourages interactions with analogs containing hydrophobic region A groups.