Computational prediction of new CYP17 inhibitors based on pharmacophore modeling, virtual screening and docking approach.

17α-Hydroxylase/C17-20-lyase (P450 17, CYP 17) is an important enzyme in the androgen biosynthesis and inhibitors of this enzyme can be used for the treatment of prostate cancer. With the aim of developing new inhibitors for the target enzyme, we generated a structure-based pharmacophore model to further explain the binding requirements for human CYP17 inhibitors. Seven common features of steroidal CYP17 inhibitors were determined using MOE software. This pharmacophore model was then used to search the Cambridge Structural Database (CSD) with the aim of developing more potent and selective CYP17 inhibitors by identifying new hits. We were able to identify 36 structures as possible active CYP17 inhibitors. Docking studies for the selected compounds from the database were also performed and the best three compounds were chosen as possible hits.