Pharmacophore Generation and Validation

Comparative Molecular Field Analysis (CoMFA), 6 16 16 755-757 pharmacophore generation and validation, 6 12 Comparative Molecular Shape Indexes Analysis (CoMSIA), J0 327t,... 

Computing properties, defined, 76 729-730 CoMSIA, pharmacophore generation and validation, 6 12 Concavalin A (Con A), 9 66-67 Concave receptor, 76 774 Concentrate, defined, 76 127 Concentration... 

Another retrospective analysis of already known H DAC inhibitors was carried out by You et al. [68]. They generated a 3D chemical-feature-based pharmacophore model and compared the ligand-based model with the structural-functional requirements for the binding of the HDAC inhibitors. Using this model, the interactions between the benzamide MS-275 and HDAC were explored. The result showed that the type and spatial location of chemical features encoded in the pharmacophore are in full agreement with the enzyme-inhibitor interaction pattern identified from molecular docking. However, also in this study no experimental validation of the modeling results was provided. 

Ekins et al. (163) used the rat ortholog 2B6 to generate a pharmacophore model and compared these findings with a partial least squares (PLS) model using MS-WHIM descriptors. The model was constructed using 16 B-lymphoblastoids and yielded a good cross-validated r2 of 0.607. The analysis included molecular surface properties (size) together with positive elec-... 

It is possible that QSAR, an empirical correlation of the data, may provide a pharmacophoric model that will be useful in next-generation drug design within this class. In such an approach, it is hoped that many of the factors which define antimalarial potency can be correlated with the structures of the analogues, and the resulting model, if valid, could be used as a predictive tool. 

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