title: Phenotypic Screening of Drug Library in Actively Differentiating Mouse Embryonic Stem Cells.
abstract: Phenotypic screening enables the discovery of new drug leads with novel targets. ES cells differentiate into different lineages by successively making use of different subsets of the genome's possible macromolecular interactions. If a compound effectively targets just one of these interactions, it derails the developmental pathway to produce a phenotypical change. The OTRADI microsource spectrum library of 2000 approved drug components, natural products, and bioactive components was screened for compounds that can induce phenotypic changes in ES cell cultures at 10 µM after 3 days. Twenty-one compounds that induced specific morphologies also induced unique changes to an expression profile of a dozen markers of early embryonic development, indicating that each compound has derailed the molecular developmental process in a characteristic way. Phenotypic screens conducted with ES cultures differentiating along different lineages can be used to efficiently prescreen compounds able to regulate cell differentiation lineage.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Billard
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA.
authors.forename: Chih-Ning
authors.initials: CN
authors.lastname: Chang
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA.
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Gross
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA OTRADI, Portland, OR, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Allen
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA chrissa.kioussi@oregonstate.edu.
authors.forename: Chrissa
authors.initials: C
authors.lastname: Kioussi
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D057166:High-Throughput Screening Assays; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010641:Phenotype; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D001685:Biological Factors; D001688:Biological Products; D015415:Biomarkers; D054852:Small Molecule Libraries
keywords: gene expression; general pharmaceutical process; high-content screening; phenotypic drug discovery; stem cells