Pharmacophore modeling and in silico screening for new P450 19 (aromatase) inhibitors

Daniela Schuster; Christian Laggner; Theodora M Steindl; Anja Palusczak; Rolf W Hartmann; Thierry Langer

doi:10.1021/ci050237k

Pharmacophore modeling and in silico screening for new P450 19 (aromatase) inhibitors

J Chem Inf Model. 2006 May-Jun;46(3):1301-11. doi: 10.1021/ci050237k.

Authors

Daniela Schuster¹, Christian Laggner, Theodora M Steindl, Anja Palusczak, Rolf W Hartmann, Thierry Langer

Affiliation

¹ Institute of Pharmacy, Department of Pharmaceutical Chemistry, University of Innsbruck, Innrain 52, A-6020 Innsbruck, Austria.

PMID: 16711749
DOI: 10.1021/ci050237k

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Algorithms
Aromatase / drug effects*
Aromatase Inhibitors / chemistry*
Aromatase Inhibitors / pharmacology*
Crystallography, X-Ray
Models, Molecular

Substances

Aromatase Inhibitors
Aromatase