Tsopelas Fotios, Giaginis Constantinos, Tsantili-Kakoulidou Anna
a Laboratory of Inorganic and Analytical Chemistry, School of Chemical Engineering , National Technical University of Athens , Athens , Greece.
b Department of Food Science and Nutrition , School of Environment, University of the Aegean , Myrina , Lemnos , Greece.
Expert Opin Drug Discov. 2017 Sep;12(9):885-896. doi: 10.1080/17460441.2017.1344210. Epub 2017 Jun 28.
Lipophilicity, expressed as the octanol-water partition coefficient, constitutes the most important property in drug action, influencing both pharmacokinetic and pharmacodynamics processes as well as drug toxicity. On the other hand, biomimetic properties defined as the retention outcome on HPLC columns containing a biological relevant agent, provide a considerable advance for rapid experimental - based estimation of ADME properties in early drug discovery stages. Areas covered: This review highlights the paramount importance of lipophilicity in almost all aspects of drug action and safety. It outlines problems brought about by high lipophilicity and provides an overview of the drug-like metrics which incorporate lower limits or ranges of logP. The fundamental factors governing lipophilicity are compared to those involved in phospholipophilicity, assessed by Immobilized Artificial Membrane Chromatography (IAM). Finally, the contribution of biomimetic properties to assess plasma protein binding is evaluated. Expert opinion: Lipophilicity and biomimetic properties have important distinct and overlapping roles in supporting the drug discovery process. Lipophilicity is unique in early drug design for library screening and for the identification of the most promising compounds to start with, while biomimetic properties are useful for the experimentally-based evaluation of ADME properties for the synthesized novel compounds, supporting the prioritization of drug candidates and guiding further synthesis.
以正辛醇 - 水分配系数表示的亲脂性是药物作用中最重要的性质，它影响着药代动力学和药效学过程以及药物毒性。另一方面，定义为在含有生物相关试剂的高效液相色谱柱上的保留结果的仿生性质，为早期药物发现阶段基于实验快速评估药物吸收、分布、代谢和排泄（ADME）性质提供了相当大的进展。涵盖领域：本综述强调了亲脂性在药物作用和安全性几乎所有方面的至关重要性。它概述了高亲脂性带来的问题，并提供了纳入logP下限或范围的类药指标的概述。将控制亲脂性的基本因素与通过固定化人工膜色谱法（IAM）评估的亲磷脂性所涉及的因素进行了比较。最后，评估了仿生性质对评估血浆蛋白结合的贡献。专家观点：亲脂性和仿生性质在支持药物发现过程中具有重要的不同和重叠作用。亲脂性在早期药物设计中对于文库筛选以及确定最有前途的起始化合物具有独特性，而仿生性质对于基于实验评估合成的新化合物的ADME性质、支持候选药物的优先级排序和指导进一步合成是有用的。
