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最大化ISRIB的潜力需要解决特异性、长期安全性以及特定疾病相关的考量因素。

Maximizing ISRIB Potential Requires Addressing Specificity, Long-term Safety, and Disease-specific Considerations.

作者信息

Boretti Alberto, Banik Bimal

机构信息

Department of Research, Melbourne institute of technology, Melbourne, Australia.

Department of Mathematics and Natural Sciences, College of Sciences and Human Studies, Deanship of Research, Prince Mohammad Bin Fahd University, Al Khobar, Kingdom of Saudi Arabia.

出版信息

Curr Med Chem. 2025;32(13):2482-2493. doi: 10.2174/0109298673290924240514061916.

Abstract

BACKGROUND

Integrated Stress Response Inhibitor (ISRIB) works by inhibiting the integrated stress response, a cellular pathway involved in the regulation of protein synthesis during stress conditions. Conditions that have been studied or suggested as potential candidates for treatment with ISRIB include neurological and metabolic disorders, cognitive impairment, viral infections, and cancer.

OBJECTIVE

The study aimed to discuss the challenges related to specificity, long-term safety, and disease-specific considerations crucial for realizing the full potential of ISRIB.

METHODS

A narrative review of the literature has been conducted to delve into ISRIB's chemistry, mechanisms of action, disease-specific considerations, and long-term safety implications.

RESULTS

While ISRIB has shown promising results in preclinical studies, more research is needed to determine its safety and effectiveness in human patients. Clinical trials are required to validate its therapeutic potential for various conditions. Despite having been proposed a decade ago, news of its clinical trials has been circulated only recently, without any published information yet and with rumors that its efficacy vs. safety profile may be compromised by side effects.

CONCLUSION

While ISRIB offers exciting prospects for a range of biomedical applications, addressing challenges related to specificity, disease-specific considerations, and importantly long-term safety, is crucial for realizing its full potential.

摘要

背景

整合应激反应抑制剂(ISRIB)通过抑制整合应激反应发挥作用,整合应激反应是一种在应激条件下参与蛋白质合成调节的细胞途径。已被研究或被认为可能用ISRIB治疗的病症包括神经和代谢紊乱、认知障碍、病毒感染和癌症。

目的

本研究旨在探讨与特异性、长期安全性以及对充分发挥ISRIB潜力至关重要的疾病特异性考虑相关的挑战。

方法

对文献进行叙述性综述,以深入研究ISRIB的化学性质、作用机制、疾病特异性考虑因素以及长期安全性影响。

结果

虽然ISRIB在临床前研究中已显示出有前景的结果,但仍需要更多研究来确定其在人类患者中的安全性和有效性。需要进行临床试验以验证其对各种病症的治疗潜力。尽管ISRIB在十年前就已被提出,但有关其临床试验的消息直到最近才流传开来,目前尚无任何已发表的信息,并有传言称其疗效与安全性可能会受到副作用的影响。

结论

虽然ISRIB为一系列生物医学应用提供了令人兴奋的前景,但应对与特异性、疾病特异性考虑因素以及重要的长期安全性相关的挑战,对于充分发挥其潜力至关重要。

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