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Review Article

作用于单胺转运体药物的最新进展和挑战

卷 27, 期 23, 2020

页: [3830 - 3876] 页: 47

弟呕挨: 10.2174/0929867325666181009123218

价格: $65

摘要

背景:人类单胺转运蛋白(hMATs)主要包括hSERT、hNET和hDAT，是治疗抑郁症和其他行为障碍的重要靶点，目前批准的药物超过30种。 目的:本文综述近年来hMATs抑制剂与中心或变构结合位点的结合模式及抑制机制的研究进展，为今后hMATs抑制剂的设计和发现提供参考。结构-活性关系(SAR)和命中/先导化合物对hMATs的选择性将在体外和体内实验中得到评价。方法:检索PubMed和Web of Science数据库，检索与hMATs相关的蛋白-配体相互作用、新型抑制剂设计和合成研究。 结果:文献数据表明，自从首次测定与氯丙咪嗪复合的同源细菌亮氨酸转运体(LeuT)的晶体结构以来，已经积累了一个包含100多个实验结构或计算模型的庞大数据库，现在定义了hMATs配体识别的结构变异性的实质性程度。与此同时，在计算模型的帮助下，药物化学已经发现一些新的hMATs抑制剂。 结论:通过实验或计算模型报道的作用于hMATs以及与不同配体复合的转运体结构的新化合物，为药物对转运体的多药理学、多模态和变构调节提供了线索。这些研究都将极大地促进对hMATs具有高活性和高选择性的新型结构支架的结构药物设计(SBDD)。

关键词: 单胺转运蛋白，变构调节，多靶向药物，常见的结合模式，药物选择性，计算模型，结构活性分析。

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