Alzheimer's disease drug development and the problem of the blood-brain barrier.

Alzheimer's disease drug development and the problem of the blood-brain barrier.
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DOI:
10.1016/j.jalz.2009.06.003
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发表时间:
2009-09
期刊:
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子:
--
通讯作者:
Pardridge WM
Pardridge WM
中科院分区:
其他
文献类型:
--
作者:
Pardridge WM

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阿尔茨海默病(AD)药物开发受到血脑屏障(BBB)存在的限制。超过98%的小分子药物和超过100%的大分子药物不能穿过BBB。尽管事实上绝大多数AD药物候选物不穿过BBB,但当今AD药物开发工作的特征在于不平衡,其中>99%的药物开发工作致力于CNS药物发现,并且<1%的药物开发致力于CNS药物递送。未来的AD药物开发需要共同努力,将BBB科学早期纳入CNS药物发现过程。这可以通过重新分配资源,扩大BBB生物学纯科学和脑药物靶向技术应用科学的努力来实现。
Alzheimer's disease (AD) drug development is limited by the presence of the blood-brain barrier (BBB). More than 98% of all small molecule drugs, and ∼100% of all large molecule drugs, do not cross the BBB. Despite the fact that the vast majority of AD drug candidates do not cross the BBB, the present-day AD drug development effort is characterized by an imbalance, whereby >99% of the drug development effort is devoted to CNS drug discovery, and <1% of drug development is devoted to CNS drug delivery. Future AD drug development needs a concerted effort to incorporate the BBB sciences early in the CNS drug discovery process. This can be accomplished by a reallocation of resources, and an expansion of the effort in the pure science of BBB biology and the applied science of brain drug targeting technology.
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