Drug-likeness ADME parameters

Calculation of drug-likeness parameters (like ADME parameters and Li-pinski s rule [43]). 

The SA protocol has also been successfully applied to optimize drug-like properties or ADME parameters while maximizing diversity and/or predicted... 

The process of drug discovery amounts to the search for optimality in a hyper-dimensional, multi-response surface area, and thus is a complex process. As discussed earlier, log P and the other R05 parameters, together with other properties such as PSA, and the number of flexible bonds, are significant contributors to a large number of models for different ADME/T properties. The open question is whether the use of such models provides an added value, compared to the simple and easily interpretable R05 criteria or the recent trends for the drug-likeness formulated by Gleeson. But can these models provide added value ... 

Importantly, the structural differences within the linker and surface recognition portion will have profound effects on subtype selectivity and physicochemical/ ADME properties of the compounds. Structural changes within these areas will hence allow for optimization and fine-tuning of the drug-like parameters that are required for a successful therapy. 

Computational methods are essential in processing the vast data streams from sequencing efforts, shuctural information, protein analysis and differential gene expression. Computational approaches serve to integrate the research, development and discovery phases. An example of such efforts is the study of drug-likeness with respect to ADME parameters, in particular BBB penetration. ... 

Appropriate characterization of drug substance and product Characterization of pharmacology and toxicology of each enantiomer with respect to potency, specificity, and maximum effect Basic understanding of stereoselectivity in ADME and PD (efficacy and safety parameters) in animal and human studies Attention to stereoselectivity in drug interactions, covariates like gender, age, ethnicity, and disease states... 

The output from the QikProp is obtained in four files, viz. qikpropameslOO. out, qikpropameslOO.mae, qikpropameslOO.qpsa and qikpropameslOO.csv. Apart from the usual physico-chemical properties, the comma-separated values (CSV) file shows the important descriptors like caco-2 and MDCK cell permeability, blood-brain barrier (logBB), HERG, CNS which are important ADME predicted parameters for a molecule to qualify as drug (Fig. 2.10). 

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