jm0512185_si_001.pdf (56.1 kB)
The Influence of Target Family and Functional Activity on the Physicochemical Properties of Pre-Clinical Compounds
journal contribution
posted on 2006-05-18, 00:00 authored by Richard MorphyThe target families of greatest interest in drug discovery can be differentiated on the basis of the
physicochemical properties of their pre-clinical ligands. The ligands for peptidergic targets, such as peptide
GPCRs and integrin receptors, possess significantly higher median property values than those for aminergic
targets, such as monoamine transporters and GPCRs. The ligands for peptide GPCRs were found to be less
efficient, in terms of their binding energy per unit of molecular weight or lipophilicity, than ligands for
monoamine GPCRs. The changes in the property values during the optimization process were found to vary
only slightly across the target families, with the main determinant of the drug-likeness of the optimized
compounds being the profile of the starting compounds. Agonists for monoamine GPCRs, opioid receptors
and ion channels were typically smaller and less lipophilic than the antagonists, but there was no difference
between the agonists and the antagonists for peptide GPCRs and nuclear receptors.