Identification of a potent and selective oxytocin antagonist, from screening a fully encoded differential release combinatorial chemical library.
A library of 1,296 1,4-benzodiazepines was prepared on 160 microM Tentagel beads. Compounds are attached to the beads using orthogonally cleavable linkers. The library was first screened as pools of 30 beads where 50% of the material is released and screened. GW405212X, a selective oxytocin antagonist, was identified by picking single beads from active pools.
Evans
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B
Department of Lead Discovery, GlaxoSmithKline Medicines Research Centre, Stevenage, Herts, UK. be0897@gsk.com
Pipe
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A
Clark
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L
Banks
M
M
D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000494:pharmacology; D016466:CHO Cells; D020650:Combinatorial Chemistry Techniques; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D020128:Inhibitory Concentration 50; D010121:Oxytocin / Q000037:antagonists & inhibitors*; D019151:Peptide Library; D018045:Receptors, Oxytocin / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection
D019151:Peptide Library; D018045:Receptors, Oxytocin; D001569:Benzodiazepines; D010121:Oxytocin