Identification of bioactive molecules by adipogenesis profiling of organic compounds
Identification of bioactive molecules by adipogenesis profiling of organic compounds
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DOI：
10.1074/jbc.m210283200
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发表时间：
2003-02-28
影响因子：
4.8
通讯作者：
Uesugi, M
中科院分区：
文献类型：
--
作者：
Choi, YM;Kawazoe, Y;Uesugi, M
后基因组药物发现的一个重要步骤是构建高质量的化学文库，以高速率生成生物活性分子。在这里，我们报告了一种基于细胞的方法来构建生物活性化合物的重点库。通过对胰岛素诱导的 3T3-L1 细胞脂肪生成的影响，从不同的库中鉴定出一系列生物活性非细胞毒性化学物质，这是培养的哺乳动物细胞中最剧烈和最敏感的形态变化之一。由此产生的重点库充分包含具有广泛药理作用的独特化合物，包括增强葡萄糖摄取、抑制细胞因子、刺激成骨和选择性抑制癌细胞。有机化合物的脂肪生成分析生成了一个针对多种生物效应的集中化学库，这些效应似乎与脂肪生成无关，就像利用蝇眼形态进行遗传筛选来识别癌基因和神经退行性基因一样。
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.