title: Rapid lead discovery through iterative screening of one bead one compound libraries.
abstract: Primary hits that arise from screening one bead one compound (OBOC) libraries against a target of interest rarely have high potency. However, there has been little work focused on the development of an efficient workflow for primary hit improvement. In this study, we show that by characterizing the binding constants for all of the hits that arise from a screen, structure-activity relationship (SAR) data can be obtained to inform the design of "derivative libraries" of a primary hit that can then be screened under more demanding conditions to obtain improved compounds. Here, we demonstrate the rapid improvement of a primary hit against matrix metalloproteinase-14 using this approach.
authors.affiliation: Departments of Chemistry and Cancer Biology The Scripps Research Institute m 130 Scripps Way, Jupiter, Florida 33458, United States.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.forename: Sabrina
authors.initials: S
authors.lastname: Amar
authors.forename: Sonia
authors.initials: S
authors.lastname: Pahwa
authors.forename: Gregg
authors.initials: G
authors.lastname: Fields
authors.forename: Thomas
authors.initials: T
authors.lastname: Kodadek
mesh_terms: D055808:Drug Discovery; D057166:High-Throughput Screening Assays; D013329:Structure-Activity Relationship
keywords: iterative screening; one bead one compound (OBOC) libraries; rapid lead discovery; structure−activity relationship (SAR)