In Silico Chemogenomics Drug Repositioning Strategies for Neglected Tropical Diseases

doi:10.2174/0929867325666180309114824
摘要

在过去几十年里，所有针对被忽视热带病的候选药物中，只有1%达到了临床试验，这突出了对新的、安全和有效的治疗方法的需求。在这种情况下，药物重新定位，即允许为已获批准的药物寻找新的适应症，而这些药物的药代动力学和安全性已经为人所知，这是对付结核分枝杆菌的一个有希望的战略。化学基因组学是典型的药物发现过程的直接后裔，该过程包括在高通量筛选(HTS)努力中，针对药物靶标系统筛选化合物，以识别先导化合物。然而，不同于单药单靶点模式，化学基因组学试图识别所有可能的靶点和疾病的所有潜在配体。在这篇综述中，我们总结了目前使用最先进的计算配体和基于结构的化学基因组学方法进行药物重新定位的方法学开发工作。此外，我们强调了基于基因组、生物和化学数据的管理和建模的一些ntd的计算药物重新定位的最新进展。此外，我们还提供了内部和其他成功的例子，并对现有的缺陷提出了可能的解决方案。
关键词: 被忽视的热带病，药物重新定位，化学基因组学，相似性搜索，机器学习，药效团，蛋白质比对，对接。
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DOI https://dx.doi.org/10.2174/0929867325666180309114824	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
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