BioSeek, a division of DiscoveRx Corporation, 310 Utah Ave., Suite 100, South San Francisco, CA 94080, USA.
Departments of Quantitative and Structural Biology, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Drop Code 0703, Indianapolis, IN 46285, USA.
Adv Drug Deliv Rev. 2014 Apr;69-70:190-204. doi: 10.1016/j.addr.2014.01.013. Epub 2014 Feb 10.
There is renewed interest in phenotypic approaches to drug discovery, using cell-based assays to select new drugs, with the goal of improving pharmaceutical success. Assays that are more predictive of human biology can help researchers achieve this goal. Primary cells are more physiologically relevant to human biology and advances are being made in methods to expand the available cell types and improve the potential clinical translation of these assays through the use of co-cultures or three-dimensional (3D) technologies. Of particular interest are assays that may be suitable for industrial scale drug discovery. Here we review the use of primary human cells and co-cultures in drug discovery and describe the characteristics of co-culture models for inflammation biology (BioMAP systems), neo-vascularization and tumor microenvironments. Finally we briefly describe technical trends that may enable and impact the development of physiologically relevant co-culture assays in the near future.
人们对基于细胞的药物发现表型方法重新产生了兴趣，旨在通过筛选新药来提高药物研发的成功率。更能预测人类生物学的检测方法可以帮助研究人员实现这一目标。原代细胞与人类生物学更相关，并且在扩展可用细胞类型的方法以及通过共培养或三维（3D）技术提高这些检测的潜在临床转化方面正在取得进展。特别感兴趣的是那些可能适合工业规模药物发现的检测方法。在这里，我们回顾了原代人细胞和共培养在药物发现中的应用，并描述了炎症生物学（BioMAP 系统）、新血管生成和肿瘤微环境共培养模型的特征。最后，我们简要描述了一些技术趋势，这些趋势可能在不久的将来使生理相关的共培养检测方法的开发成为可能并产生影响。
