Scaffold Ranking and Positional Scanning Identify Novel Neurite Outgrowth Promoters with Nanomolar Potency
Scaffold Ranking and Positional Scanning Identify Novel Neurite Outgrowth Promoters with Nanomolar Potency
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DOI：
10.1021/acsmedchemlett.8b00425
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发表时间：
2018-10-01
影响因子：
4.2
通讯作者：
Giulianotti, Marc A.
中科院分区：
文献类型：
--
作者：
Al-Ali, Hassan;Debevec, Ginamarie;Giulianotti, Marc A.
中枢神经系统（CNS）神经元在损伤后通常不能再生轴突。损伤中枢神经系统轴突和破坏神经回路的损伤或神经病变通常会导致永久性功能缺陷。因此，轴突再生是许多中枢神经系统疾病的一种强烈追求的治疗策略。利用原代神经元的表型筛选已被证明能够成功地识别促进体内轴突再生的药物。在这里，我们报道了利用初级中枢神经系统神经元在表型分析中筛选基于混合物的组合小分子文库，并发现了具有低纳米摩尔效力的神经突生长促进剂。
Central nervous system (CNS) neurons typically fail to regrow their axons after injury. Injuries or neuropathies that damage CNS axons and disrupt neuronal circuitry often result in permanent functional deficits. Axon regeneration is therefore an intensely pursued therapeutic strategy for numerous CNS disorders. Phenotypic screens utilizing primary neurons have proven successful at identifying agents that promote axon regeneration in vivo. Here, we report the screening of mixture based combinatorial small molecule libraries in a phenotypic assay utilizing primary CNS neurons and the discovery of neurite outgrowth promoters with low nanomolar potency.