Application of Pharmacophore Models in Virtual Screening

As shown in the previous section, there have been an impressive number of new approaches and tools appearing in the field of structure- and ligand-based pharmacophore modeling. All of them address slightly different issues and therefore a combination of several methods, as shown in different application examples, can significantly enhance the chances of success. 

Schuster et al developed ligand-based pharmacophore models for 11 (3-hydroxysteroid dehydrogenase (11(3-HSD) inhibitors.By VS they were able to identify inhibitors of this enzyme active in the nanomolar range. 

Some hits also revealed sufficient selectivity of type 1 inhibition versus the type 2 isoform, which is advantageous for the side-effect profile of these compounds. Comparison of the model for llp-HSDl inhibitors with the X-ray crystal structure (which was published shortly after model generation and VS) showed good correlation of the chemical features responsible for ligand binding. In another study, a combination of common feature-based qualitative and quantitative models was used as 3D pharmacophore search query to successfully detect novel endothelin-A antagonistic lead structures. 

The pharmacophore-based screening approach has recently been shown to be also very successful for the identification of bio-active natural products. Rollinger et derived a structure-based pharmacophore model on the 

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