Pharmacophore modeling and in silico screening for new P450 19 (aromatase) inhibitors.
Cytochrome P450 19 (P450 19, aromatase) constitutes a successful target for the treatment of breast cancer. This study analyzes chemical features common to P450 19 inhibitors to develop ligand-based, selective pharmacophore models for this enzyme. The HipHop and HypoRefine algorithms implemented in the Catalyst software package were employed to create both common feature and quantitative models. The common feature model for P450 19 includes two ring aromatic features in its core and two hydrogen bond acceptors at the ends. The models were used as database search queries to identify active compounds from the NCI database.
Schuster
Daniela
D
Institute of Pharmacy, Department of Pharmaceutical Chemistry, University of Innsbruck, Innrain 52, A-6020 Innsbruck, Austria.
Laggner
Christian
C
Steindl
Theodora M
TM
Palusczak
Anja
A
Hartmann
Rolf W
RW
Langer
Thierry
T
D000465:Algorithms; D001141:Aromatase / Q000187:drug effects*; D047072:Aromatase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D008958:Models, Molecular
D047072:Aromatase Inhibitors; D001141:Aromatase