A Highly Automated Assay for Determining the Aqueous Equilibrium Solubility of Drug Discovery Compounds
A Highly Automated Assay for Determining the Aqueous Equilibrium Solubility of Drug Discovery Compounds
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DOI：
10.1016/j.jala.2010.10.002
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发表时间：
2011-08-01
期刊：
影响因子：
--
通讯作者：
Barton, Patrick
中科院分区：
文献类型：
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作者：
Wenlock, Mark C.;Austin, Rupert P.;Barton, Patrick
水溶解度是任何潜在药物候选物的重要物理化学参数，并且高通量动力学测定经常用于药物发现以给出化合物的水溶解度的估计。然而，来自平衡（热力学）摇瓶技术的水溶解度数据被认为更相关，但生成更慢且更劳动密集。描述了一种高度自动化的水平衡溶解度摇瓶技术，并对一组15种市售药物进行了验证，其水溶解度涵盖了四个数量级。该测定使用Tecan Freedom Evo 200液体处理机器人（Tecan Group Ltd.，Mannerdorf，Switzerland），其具有用于样品管的运输、开盖和再盖以及离心的集成器具。这些定制的自动化解决方案有助于克服与执行传统的金标准水平衡溶解度摇瓶测量相关的劳动密集型步骤，使该测定能够用作初级波药物发现筛选。(JALA 2011;16：276-84）
Aqueous solubility is an important physicochemical parameter for any potential drug candidate, and high-throughput kinetic assays are frequently used in drug discovery to give an estimate of a compound's aqueous solubility. However, the aqueous solubility data from an equilibrium (thermodynamic) shake-flask technique is considered more relevant, but is slower and more labor intensive to generate. A highly automated aqueous equilibrium solubility shake-flask technique is described and validated on a set of 15 marketed drugs, whose aqueous solubilities cover four orders of magnitude. The assay uses a Tecan Freedom Evo 200 liquid handling robot (Tecan Group Ltd., Mannerdorf, Switzerland) with integrated appliances for the transportation, decapping and recapping, and centrifugation of sample tubes. These bespoke automation solutions help overcome the labor intensive steps associated with performing conventional, gold standard, aqueous equilibrium solubility shake-flask measurements, enabling the assay to be used as a primary-wave drug discovery screen. (JALA 2011;16:276-84)