title: Deconvolution of combinatorial libraries for drug discovery: experimental comparison of pooling strategies.
abstract: An experimental evaluation of several different pooling strategies for combinatorial libraries was conducted using a library of 810 compounds and an enzyme inhibition assay (phospholipase A2). The library contained compounds with varying degrees of activity as well as inactive compounds. The compounds were synthesized in groups of three and pooled together in various formats to realize different pooling strategies. With one exception, all iterative deconvolution strategies and position scanning resulted in identification of the same compound. The results are in good agreement with the predicted outcome from theoretical and computational methods. These data support the tenet that active compounds for pharmaceutically relevant targets can be successfully identified from combinatorial libraries organized in mixtures.
authors.affiliation: ISIS Pharmaceuticals, Carlsbad, California 92008, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wilson-Lingardo
authors.forename: P W
authors.initials: PW
authors.lastname: Davis
authors.forename: D J
authors.initials: DJ
authors.lastname: Ecker
authors.forename: N
authors.initials: N
authors.lastname: Hébert
authors.forename: O
authors.initials: O
authors.lastname: Acevedo
authors.forename: K
authors.initials: K
authors.lastname: Sprankle
authors.forename: T
authors.initials: T
authors.lastname: Brennan
authors.forename: L
authors.initials: L
authors.lastname: Schwarcz
authors.forename: S M
authors.initials: SM
authors.lastname: Freier
authors.forename: J R
authors.initials: JR
authors.lastname: Wyatt
mesh_terms: D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005069:Evaluation Studies as Topic; D006801:Humans; D015394:Molecular Structure; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2
chemical_list: D010726:Phosphodiesterase Inhibitors; D010741:Phospholipases A; D054467:Phospholipases A2