筛选好的‘药物样’属性来优化小分子血脑屏障穿透

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.

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