Abstract
Drug-target binding affinity and pharmacokinetics are equally important factors of drug design. Simple molecular properties such as molecular size have been used as pharmacokinetic and/or drug-likeness filters during chemical library design and also correlated with binding affinity. In the present study, current property filters are reviewed, a collection of their optimal values is provided, and a statistical framework is introduced allowing calibration of their selectivity and sensitivity for drugs. The role of ligand efficiency indices in drug design is also described. It is concluded that the usefulness of property filters of molecular size and lipophilicity is limited as predictors of general drug-likeness. However, they demonstrate increased performance in specific cases, e.g. in central nervous system diseases, emphasizing their future importance in specific, disease-focused library design instead of general drug-likeness filtering.
Keywords: Binding site, entropy, free energy, molecule, pocket, protein, structure, target, logP, Wiener index
Current Medicinal Chemistry
Title:Molecular Property Filters Describing Pharmacokinetics and Drug Binding
Volume: 19 Issue: 11
Author(s): A. T. Garcia-Sosa, U. Maran and C. Hetenyi
Affiliation:
Keywords: Binding site, entropy, free energy, molecule, pocket, protein, structure, target, logP, Wiener index
Abstract: Drug-target binding affinity and pharmacokinetics are equally important factors of drug design. Simple molecular properties such as molecular size have been used as pharmacokinetic and/or drug-likeness filters during chemical library design and also correlated with binding affinity. In the present study, current property filters are reviewed, a collection of their optimal values is provided, and a statistical framework is introduced allowing calibration of their selectivity and sensitivity for drugs. The role of ligand efficiency indices in drug design is also described. It is concluded that the usefulness of property filters of molecular size and lipophilicity is limited as predictors of general drug-likeness. However, they demonstrate increased performance in specific cases, e.g. in central nervous system diseases, emphasizing their future importance in specific, disease-focused library design instead of general drug-likeness filtering.
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Cite this article as:
T. Garcia-Sosa A., Maran U. and Hetenyi C., Molecular Property Filters Describing Pharmacokinetics and Drug Binding, Current Medicinal Chemistry 2012; 19 (11) . https://dx.doi.org/10.2174/092986712799945021
DOI https://dx.doi.org/10.2174/092986712799945021 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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