Kinase targets in CNS drug discovery
Kinase targets in CNS drug discovery
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中枢神经系统药物发现中的激酶靶标
DOI：
10.4155/fmc-2016-0214
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发表时间：
2017-03-01
影响因子：
4.2
通讯作者：
Kassiou, Michael
中科院分区：
文献类型：
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作者：
Gunosewoyo, Hendra;Yu, Lifang;Kassiou, Michael
激酶最初被认为是不可药用的，对制药公司和学术界来说是有吸引力的药物靶点。迄今为止，有超过40种激酶抑制剂被美国FDA批准，其中32种是小分子，除了三种哺乳动物靶向雷帕霉素抑制剂大环内酯类（西罗莫司、替西罗莫司和依维莫司）之外。尽管用于癌症的激酶抑制剂发展迅速，但目前这些药物中没有一种被批准用于CNS适应症。这一微型视角突出了CNS疾病的选定激酶靶点，其中报道了脑渗透性小分子抑制剂，并证明了临床前概念验证的疗效。其次是简要讨论在开发用于CNS疾病的激酶抑制剂中血脑屏障渗透和选择性概况的关键挑战。
Originally thought to be nondruggable, kinases represent attractive drug targets for pharmaceutical companies and academia. To date, there are over 40 kinase inhibitors approved by the US FDA, with 32 of these being small molecules, in addition to the three mammalian target of rapamycin inhibitor macrolides ( sirolimus, temsirolimus and everolimus). Despite the rapid development of kinase inhibitors for cancer, presently none of these agents are approved for CNS indications. This mini perspective highlights selected kinase targets for CNS disorders, of which brain-permeable small-molecule inhibitors are reported, with demonstrated preclinical proof-of-concept efficacy. This is followed by a brief discussion on the key challenges of blood-brain barrier penetration and selectivity profiles in developing kinase inhibitors for CNS disorders.