SRI International, Biosciences Division, Menlo Park CA United States.
SRI International, Biosciences Division, Menlo Park CA United States.
Life Sci Space Res (Amst). 2022 Nov;35:30-35. doi: 10.1016/j.lssr.2022.07.002. Epub 2022 Jul 14.
The discovery of safe and effective radiation countermeasures (MCM) for long-duration spaceflight is challenging due to the complexity of the space radiation biology and high safety requirements. There are few if any clinically-validated molecular targets for this use case, and preclinical models have several known limitations. These challenges make the evaluation of existing FDA-approved drugs for this indication, or drug repurposing, an attractive strategy to accelerate space radiation countermeasure development. Drug repurposing offers several advantages over de novo drug discovery including established manufacturing methods, human clinical safety data, and well-understood dosing and pharmacokinetic considerations. There are limitations working with a fixed set of possible candidate compounds, but some properties of repurposed drugs can be tailored for well-defined new indications through reformulation and development of drug combinations. Drug repurposing is thus an attractive strategy for mitigating the high risks and costs of drug development and delivering new countermeasures to protect human from space radiation in long-term missions.
由于空间辐射生物学的复杂性和高安全性要求,发现安全有效的辐射对策(MCM)对于长时间的太空飞行是具有挑战性的。对于这种用途,几乎没有经过临床验证的分子靶标,而且临床前模型存在几个已知的局限性。这些挑战使得评估现有的 FDA 批准药物用于该适应症,或药物重新定位,成为加速空间辐射对策开发的一种有吸引力的策略。药物重新定位相对于从头发现药物具有几个优势,包括已建立的制造方法、人类临床安全性数据以及充分了解的剂量和药代动力学考虑因素。使用固定的可能候选化合物集存在局限性,但通过重新配方和药物组合的开发,可以针对明确的新适应症调整重新定位药物的某些特性。因此,药物重新定位是减轻药物开发高风险和高成本并为长期任务中的人类提供新的辐射对策的一种有吸引力的策略。