Institute for Drug Discovery, Purdue University, West Lafayette IN 47907 USA.
Department of Pharmacology and Chemical Biology and Emory Chemical Biology Discovery Center, Emory University School of Medicine, Atlanta, GA 30322 USA.
Life Sci Space Res (Amst). 2022 Nov;35:88-104. doi: 10.1016/j.lssr.2022.07.004. Epub 2022 Jul 21.
As humanity begins to venture further into space, approaches to better protect astronauts from the hazards found in space need to be developed. One particular hazard of concern is the complex radiation that is ever present in deep space. Currently, it is unlikely enough spacecraft shielding could be launched that would provide adequate protection to astronauts during long-duration missions such as a journey to Mars and back. In an effort to identify other means of protection, prophylactic radioprotective drugs have been proposed as a potential means to reduce the biological damage caused by this radiation. Unfortunately, few radioprotectors have been approved by the FDA for usage and for those that have been developed, they protect normal cells/tissues from acute, high levels of radiation exposure such as that from oncology radiation treatments. To date, essentially no radioprotectors have been developed that specifically counteract the effects of chronic low-dose rate space radiation. This review highlights how high-throughput screening (HTS) methodologies could be implemented to identify such a radioprotective agent. Several potential target, pathway, and phenotypic assays are discussed along with potential challenges towards screening for radioprotectors. Utilizing HTS strategies such as the ones proposed here have the potential to identify new chemical scaffolds that can be developed into efficacious radioprotectors that are specifically designed to protect astronauts during deep space journeys. The overarching goal of this review is to elicit broader interest in applying drug discovery techniques, specifically HTS towards the identification of radiation countermeasures designed to be efficacious towards the biological insults likely to be encountered by astronauts on long duration voyages.
随着人类开始进一步探索太空，需要开发更好的方法来保护宇航员免受太空中的危险。一个特别令人关注的危险是深空中无处不在的复杂辐射。目前，不太可能发射足够的航天器屏蔽层，为宇航员在长时间任务（如往返火星的任务）中提供足够的保护。为了寻找其他保护方法，预防性辐射防护药物已被提议作为减少这种辐射造成的生物损伤的潜在手段。不幸的是，很少有辐射防护剂被 FDA 批准用于使用，而且对于那些已经开发的辐射防护剂，它们只能保护正常细胞/组织免受急性、高水平的辐射暴露，如肿瘤放疗。迄今为止，基本上没有开发出专门对抗慢性低剂量率空间辐射影响的辐射防护剂。这篇综述强调了如何实施高通量筛选 (HTS) 方法来识别这种辐射防护剂。讨论了几种潜在的靶标、途径和表型测定方法，以及筛选辐射防护剂的潜在挑战。利用 HTS 策略，如本文中提出的策略，有可能识别出新的化学支架，这些化学支架可以开发成有效的辐射防护剂，专门用于保护宇航员在深空旅行中的安全。这篇综述的总体目标是引起人们对应用药物发现技术的广泛兴趣，特别是针对可能在长期航行中遇到的宇航员生物损伤的高效辐射对策的 HTS。
