Identification of bioactive molecules by adipogenesis profiling of organic compounds.
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.
Choi
Yongmun
Y
The Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Kawazoe
Yoshinori
Y
Murakami
Koji
K
Misawa
Hiroyuki
H
Uesugi
Motonari
M
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
D016207:Cytokines; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D007335:Insulin-Like Growth Factor II; D005947:Glucose