Univ Lille Nord de France, F-59000 Lille, France.
Drug Discov Today. 2012 Apr;17(7-8):285-90. doi: 10.1016/j.drudis.2011.10.006. Epub 2011 Oct 20.
Several parameters influencing the brain distribution of compounds must be considered when designing potential neuropharmaceuticals in early-stage drug discovery. The blood-brain barrier (BBB) represents an obstacle for drug penetration into the brain. Many in vitro BBB models have proven useful for predicting the BBB permeation rate, but do not meet all criteria for use in early-stage drug discovery: feasibility, rapidity, reliability and a low requirement for human resources. To meet this demand, we have developed a robust, higher-throughput, cell-based model exhibiting BBB features (low paracellular permeability, functional efflux pumps and the correct endothelial phenotype). This system comes in a ready-to-use, frozen format, appropriate for in-house use by large pharmaceutical firms and small biotech companies during early-stage drug discovery.
在早期药物发现阶段设计潜在的神经药物时，必须考虑影响化合物脑分布的几个参数。血脑屏障 (BBB) 是药物进入大脑的障碍。许多体外 BBB 模型已被证明可用于预测 BBB 渗透率，但不符合早期药物发现使用的所有标准：可行性、快速性、可靠性和对人力资源的低要求。为了满足这一需求，我们开发了一种稳健、高通量、具有 BBB 特征的基于细胞的模型（低旁通透性、功能性外排泵和正确的内皮表型）。该系统采用即用型冷冻格式，适合大型制药公司和小型生物技术公司在早期药物发现阶段内部使用。
