摘要
被开发用于治疗中枢神经系统(CNS)疾病的药物达到临床批准的成功率是所有疾病属性中最低的。导致成功率低的很大原因是小分子透过血脑屏障(一个由毛细内皮血管紧密连接,用来排出脑内异物的屏障)的失败。血脑屏障穿透小分子的设计已然成为一个深入研究的课题,并得出了一系列用来得到血脑屏障穿透最大可能性尝试的指导。这个综述分析了筛选血脑屏障分子各种理化属性重要性排名的思考的现在情形,描述模型系统来决定血脑屏障穿透,总结数据分析方法和提供一个此领域进一步发展的前景。
关键词: 血脑屏障,药物样,中枢神经系统,神经药理学,理化性质,药物设计。
Current Medicinal Chemistry
Title:Selecting Good ‘Drug-Like’ Properties to Optimize Small Molecule Blood-Brain Barrier Penetration
Volume: 23 Issue: 14
Author(s): Paul C. Trippier
Affiliation:
关键词: 血脑屏障,药物样,中枢神经系统,神经药理学,理化性质,药物设计。
摘要: The success rate to achieve clinical approval of drugs developed to treat diseases of the central nervous system (CNS) is the lowest of all disease indications. A large contributor to this poor success rate is failure of small molecules to pass through the blood-brain barrier (BBB), a barrier composed of capillary endothelial cells connected by tight junctions that functions to extrude xenobiotics from the brain. Designing small molecules to be BBB penetrant has been the subject of intensive research and has resulted in a series of guidelines to attain the best possible chances of BBB penetration. This review will analyze the current state of thinking in ranking the importance of various physicochemical properties required to select BBB penetrant molecules, describe model systems to determine BBB penetration, summarize data analysis methods and provide an outlook on further developments in the field.
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Cite this article as:
Paul C. Trippier , Selecting Good ‘Drug-Like’ Properties to Optimize Small Molecule Blood-Brain Barrier Penetration, Current Medicinal Chemistry 2016; 23 (14) . https://dx.doi.org/10.2174/0929867323666160405112353
DOI https://dx.doi.org/10.2174/0929867323666160405112353 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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