title: Identification of bioactive molecules by adipogenesis profiling of organic compounds.
abstract: An important step in the postgenomic drug discovery is the construction of high quality chemical libraries that generate bioactive molecules at high rates. Here we report a cell-based approach to composing a focused library of biologically active compounds. A collection of bioactive non-cytotoxic chemicals was identified from a divergent library through the effects on the insulin-induced adipogenesis of 3T3-L1 cells, one of the most drastic and sensitive morphological alterations in cultured mammalian cells. The resulting focused library amply contained unique compounds with a broad range of pharmacological effects, including glucose-uptake enhancement, cytokine inhibition, osteogenesis stimulation, and selective suppression of cancer cells. Adipogenesis profiling of organic compounds generates a focused chemical library for multiple biological effects that are seemingly unrelated to adipogenesis, just as genetic screens with the morphology of fly eyes identify oncogenes and neurodegenerative genes.
authors.affiliation: The Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Yongmun
authors.initials: Y
authors.lastname: Choi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kawazoe
authors.forename: Koji
authors.initials: K
authors.lastname: Murakami
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Misawa
authors.forename: Motonari
authors.initials: M
authors.lastname: Uesugi
mesh_terms: D016475:3T3 Cells; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D051379:Mice; D008956:Models, Chemical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D007335:Insulin-Like Growth Factor II; D005947:Glucose