State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing, China.
Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, China.
Med Res Rev. 2024 May;44(3):975-1012. doi: 10.1002/med.22009. Epub 2023 Dec 21.
Ischemic stroke (IS) poses a significant threat to global human health and life. In recent decades, we have witnessed unprecedented progresses against IS, including thrombolysis, thrombectomy, and a few medicines that can assist in reopening the blocked brain vessels or serve as standalone treatments for patients who are not eligible for thrombolysis/thrombectomy therapies. However, the narrow time windows of thrombolysis/thrombectomy, coupled with the risk of hemorrhagic transformation, as well as the lack of highly effective and safe medications, continue to present big challenges in the acute treatment and long-term recovery of IS. In the past 3 years, several excellent articles have reviewed pathophysiology of IS and therapeutic medicines for the treatment of IS based on the pathophysiology. Regretfully, there is no comprehensive overview to summarize all categories of anti-IS drugs/agents designed and synthesized based on molecular mechanisms of IS pathophysiology. From medicinal chemistry view of point, this article reviews a multitude of anti-IS drugs/agents, including small molecule compounds, natural products, peptides, and others, which have been developed based on the molecular mechanism of IS pathophysiology, such as excitotoxicity, oxidative/nitrosative stresses, cell death pathways, and neuroinflammation, and so forth. In addition, several emerging medicines and strategies, including nanomedicines, stem cell therapy and noncoding RNAs, which recently appeared for the treatment of IS, are shortly introduced. Finally, the perspectives on the associated challenges and future directions of anti-IS drugs/agents are briefly provided to move the field forward.
缺血性脑卒中(IS)对全球人类健康和生命构成重大威胁。近几十年来,我们见证了针对 IS 的前所未有的进展,包括溶栓、取栓以及几种可以帮助重新开放阻塞的脑血管或作为不适合溶栓/取栓治疗的患者的单独治疗方法的药物。然而,溶栓/取栓的时间窗口狭窄,加上出血转化的风险,以及缺乏高效和安全的药物,继续在 IS 的急性治疗和长期康复方面带来巨大挑战。在过去的 3 年中,有几篇优秀的文章根据病理生理学综述了 IS 的病理生理学和治疗 IS 的治疗药物。遗憾的是,没有全面的综述来总结基于 IS 病理生理学分子机制设计和合成的所有类别抗 IS 药物/制剂。从药物化学的角度来看,本文综述了许多抗 IS 药物/制剂,包括小分子化合物、天然产物、肽等,这些药物/制剂是基于 IS 病理生理学的分子机制,如兴奋性毒性、氧化/硝化应激、细胞死亡途径和神经炎症等开发的。此外,还简要介绍了几种新兴的用于治疗 IS 的药物和策略,包括纳米医学、干细胞疗法和非编码 RNA。最后,简要提供了关于抗 IS 药物/制剂相关挑战和未来方向的观点,以推动该领域的发展。