Abassi Yama A, Xi Biao, Zhang Wenfu, Ye Peifang, Kirstein Shelli L, Gaylord Michelle R, Feinstein Stuart C, Wang Xiaobo, Xu Xiao
ACEA Biosciences, 6779 Mesa Ridge Road, San Diego, CA 92121, USA.
Chem Biol. 2009 Jul 31;16(7):712-23. doi: 10.1016/j.chembiol.2009.05.011.
We describe a cell-based kinetic profiling approach using impedance readout for monitoring the effect of small molecule compounds. This noninvasive readout allows continuous sampling of cellular responses to biologically active compounds and the ensuing kinetic profile provides information regarding the temporal interaction of compounds with cells. The utility of this approach was tested by screening a library containing FDA approved drugs, experimental compounds, and nature compounds. Compounds with similar activity produced similar impedance-based time-dependent cell response profiles (TCRPs). The compounds were clustered based on TCRP similarity. We identified novel mechanisms for existing drugs, confirmed previously reported calcium modulating activity for COX-2 inhibitor celecoxib, and identified an additional mechanism for the experimental compound monastrol. We also identified and characterized a new antimitotic agent. Our findings indicate that the TCRP approach provides predictive mechanistic information for small molecule compounds.
我们描述了一种基于细胞的动力学分析方法，该方法利用阻抗读数来监测小分子化合物的作用。这种非侵入性读数允许对细胞对生物活性化合物的反应进行连续采样，随后的动力学曲线提供了有关化合物与细胞时间相互作用的信息。通过筛选一个包含FDA批准药物、实验化合物和天然化合物的文库来测试这种方法的实用性。具有相似活性的化合物产生了相似的基于阻抗的时间依赖性细胞反应曲线（TCRP）。根据TCRP相似性对化合物进行聚类。我们确定了现有药物的新机制，证实了先前报道的COX-2抑制剂塞来昔布的钙调节活性，并确定了实验化合物monastrol的另一种机制。我们还鉴定并表征了一种新的抗有丝分裂剂。我们的研究结果表明，TCRP方法为小分子化合物提供了预测性的作用机制信息。
