医学
血脑屏障
药物发现
限制
奥西默替尼
中枢神经系统
药品
药理学
肿瘤科
生物信息学
内科学
埃罗替尼
表皮生长因子受体
生物
癌症
工程类
机械工程
作者
Nicola Colclough,Kan Chen,Peter Johnström,Markus Fridén,Dermot F. McGinnity
标识
DOI:10.1016/j.drudis.2019.01.015
摘要
Due to the blood-brain barrier (BBB) limiting the exposure of therapeutics to the central nervous system (CNS), patients with brain malignancies are challenging to treat, typically have poor prognoses, and represent a significant unmet medical need. Preclinical data report osimertinib to have significant BBB penetration and emerging clinical data demonstrate encouraging activity against CNS malignancies. Here, we discuss the oncology drug candidates AZD3759 and AZD1390 as case examples of discovery projects designing in BBB penetrance. We demonstrate how these innovative kinase inhibitors were recognized as brain penetrant and outline our view of experimental approaches and strategies that can facilitate the discovery of new brain-penetrant therapies for the treatment of primary and secondary CNS malignancies as well as other CNS disorders.
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