title: Biodiversity of small molecules--a new perspective in screening set selection.
abstract: How is the 'diversity' of a compound set defined and how is the most appropriate compound subset identified for assay when screening the entire HTS deck is not an option? A common approach has so far been to cover as much of the chemical space as possible by screening a chemically diverse set of compounds. We show that, rather than chemical diversity, the biologic diversity of a compound library is an essential requirement for hit identification. We describe a simple and efficient approach for the design of a HTS library based on compound-target diversity. Biodiverse compound subsets outperform chemically diverse libraries regarding hit rate and the total number of unique chemical scaffolds present among hits. Specifically, by screening ~19% of a HTS collection, we expect to discover ~50-80% of all desired bioactive compounds.
authors: Cheminformatics and Statistics, Hoffmann-La Roche, Grenzacherstrasse 124, 4070, Basel, Switzerland.
authors: Paula M
authors: PM
authors: Petrone
authors: Anne Mai
authors: AM
authors: Wassermann
authors: Eugen
authors: E
authors: Lounkine
authors: Peter
authors: P
authors: Kutchukian
authors: Benjamin
authors: B
authors: Simms
authors: Jeremy
authors: J
authors: Jenkins
authors: Paul
authors: P
authors: Selzer
authors: Meir
authors: M
authors: Glick
mesh_terms: D000465:Algorithms; D000818:Animals; D057225:Data Mining; D062126:Databases, Chemical; D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays; D006801:Humans; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010600:Pharmacology; D012189:Retrospective Studies; D054852:Small Molecule Libraries; D013329:Structure-Activity Relationship
chemical_list: D004364:Pharmaceutical Preparations; D054852:Small Molecule Libraries