Generation of a Focused Set of GSK Compounds Biased toward Ligand-Gated Ion-Channel Ligands

摘要

A "data mining" methodology based on substructural analysis and standard 1024 Daylight fingerprints as descriptors was applied to a set of known antagonists of a subfamily of ligand-gated ion channels comprising nicotinic acetylcholine receptors (nAChR's),5-hydroxytryptamine,gamma-amino butyric acid-A,and glycine receptors.The derived scoring function was used to generate a focused set that was screened for alpha7 nAChR,resulting in the identification of novel alpha7 ligands easily amenable to chemical modification.Finally,the same scoring function was applied retrospectively to other in-house sets screened for the same target in the same assay.The results and performance of the method are described in detail.