Future Medicinal Chemistry 2014-01-01

Pharmacophore modeling for COX-1 and -2 inhibitors with LigandScout in comparison to Discovery Studio.

Veronika Temml, Teresa Kaserer, Zsofia Kutil, Premysl Landa, Tomas Vanek, Daniela Schuster

Index: Future Med. Chem. 6(17) , 1869-81, (2014)

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Abstract

Pharmacophore modeling has become an integrated tool in drug discovery. However, no prospective study compares the performance of the available software.The two widely used pharmacophore modeling and screening software programs Discovery Studio and LigandScout were used to generate, validate, and prospectively apply COX-1 and -2 models. Selected virtual hits were tested in cell-free enzymatic assays. The correct retrieval of active compounds was compared.In the enzymatic testing, 10.5% of the tested hits for COX-2 and 6.6% of the predicted compounds for COX-1 were active. To directly compare the two models, both based on the same PDB entry, were selected for virtual screening. The two programs yielded vastly different hit lists, but both predicted active compounds.To obtain a comprehensive selection of active compounds, more than one program should be used for modeling.