Maximizing ISRIB Potential Requires Addressing Specificity, Long-Term Safety, and Disease-Specific Considerations

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. Method: 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.