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

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-hydroxytryptarnine, gamma-amino butyric acid-A, and glycine receptors. The derived scoring function was used to generate a focused set that was screened for alpha 7 nAChR, resulting in the identification of novel alpha 7 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.