Ligand-based Pharmacophore Modeling

In the ligand-based approach, a pharmacophore is deduced from the arranged key interactions of active ligands - having the same binding mode to the 

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In this chapter, we have tried to demonstrate the great diversity of software tools available to the researcher in the area of ligand-based pharmacophore modeling. With the expansion of combinatorial chemistry techniques and the need to manipulate very large amounts of real or virtual chemical data, pharmacophore-... 

A lot of effort has been invested over the past 20 years in the optimization of the different steps of pharmacophore generation molecular editing and 3D representation, combinatorial enumeration, conformational expansion and pharmacophore perception methodologies for small drug-like data sets. However, we note that today there are still some areas with potential for improvement in the field of ligand-based pharmacophore modeling ... 

Schmetzer et al. [27] performed a joint CoMFA and Yak study for 31 cannabi-noids acting on the CB1 receptor. Starting from a ligand-based pharmacophore model, a classical CoMFA investigation was accomplished yielding a correlation... 

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. 

The application of pharmacophore-based screening of chemical databases has led to the discovery of several synthetic leads for promising drug targets. The following two application examples represent a typical structure-based and ligand-based pharmacophore modeling study, respectively. 

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