Rapamycin: From Microbial Discovery to Therapeutic Innovations — Advances, Challenges, and Future Prospects

Malak Guermit; Mohamed Marouf Aribi

doi:10.5455/JPPR.20251229122615

J Pharmacol Pharm Res. 2026; 3(2): 7-19

doi: 10.5455/JPPR.20251229122615

Rapamycin: From Microbial Discovery to Therapeutic Innovations — Advances, Challenges, and Future Prospects

Malak Guermit, Mohamed Marouf Aribi.

Abstract
Abstract
Rapamycin (sirolimus), originally isolated from Streptomyces hygroscopicus, is a macrolide compound that has profoundly influenced modern biomedical research through its inhibition of the mechanistic target of rapamycin (mTOR) pathway. This review synthesizes current knowledge on its microbiological origin, molecular mechanisms, therapeutic applications, and biotechnological optimization, with particular emphasis on recent advances and emerging challenges. A comprehensive analysis of peer-reviewed literature was conducted, focusing on rapamycin biosynthesis, mTOR signaling, clinical uses, and production strategies. Overall, rapamycin and its analogs (rapalogs) demonstrate significant clinical value in areas such as transplantation, oncology, neurodegenerative diseases, and aging research. Recent advances in metabolic engineering, synthetic biology, and nanodelivery systems have markedly enhanced production yields and improved pharmacological performance; however, important limitations persist, including poor solubility, limited bioavailability, metabolic side effects, and concerns regarding long-term safety. Despite these challenges, rapamycin remains a cornerstone molecule bridging microbial natural products and translational medicine, and continued efforts to optimize its production and achieve selective modulation of mTOR signaling will be essential to fully expand its future therapeutic potential.

Key words: Keywords : rapamycin ; mTOR signalling ; Streptomyces;Rapalogs ; pharmacology; biotechnology.

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Pubmed Style

Guermit M, Aribi MM. Rapamycin: From Microbial Discovery to Therapeutic Innovations — Advances, Challenges, and Future Prospects. J Pharmacol Pharm Res. 2026; 3(2): 7-19. doi:10.5455/JPPR.20251229122615

Web Style

Guermit M, Aribi MM. Rapamycin: From Microbial Discovery to Therapeutic Innovations — Advances, Challenges, and Future Prospects. https://www.wisdomgale.com/jppr/?mno=304896 [Access: June 26, 2026]. doi:10.5455/JPPR.20251229122615

AMA (American Medical Association) Style

Guermit M, Aribi MM. Rapamycin: From Microbial Discovery to Therapeutic Innovations — Advances, Challenges, and Future Prospects. J Pharmacol Pharm Res. 2026; 3(2): 7-19. doi:10.5455/JPPR.20251229122615

Vancouver/ICMJE Style

Guermit M, Aribi MM. Rapamycin: From Microbial Discovery to Therapeutic Innovations — Advances, Challenges, and Future Prospects. J Pharmacol Pharm Res. (2026), [cited June 26, 2026]; 3(2): 7-19. doi:10.5455/JPPR.20251229122615

Harvard Style

Guermit, M. & Aribi, . M. M. (2026) Rapamycin: From Microbial Discovery to Therapeutic Innovations — Advances, Challenges, and Future Prospects. J Pharmacol Pharm Res, 3 (2), 7-19. doi:10.5455/JPPR.20251229122615

Turabian Style

Guermit, Malak, and Mohamed Marouf Aribi. 2026. Rapamycin: From Microbial Discovery to Therapeutic Innovations — Advances, Challenges, and Future Prospects. Journal of Pharmacological and Pharmaceutical Research, 3 (2), 7-19. doi:10.5455/JPPR.20251229122615

Chicago Style

Guermit, Malak, and Mohamed Marouf Aribi. "Rapamycin: From Microbial Discovery to Therapeutic Innovations — Advances, Challenges, and Future Prospects." Journal of Pharmacological and Pharmaceutical Research 3 (2026), 7-19. doi:10.5455/JPPR.20251229122615

MLA (The Modern Language Association) Style

Guermit, Malak, and Mohamed Marouf Aribi. "Rapamycin: From Microbial Discovery to Therapeutic Innovations — Advances, Challenges, and Future Prospects." Journal of Pharmacological and Pharmaceutical Research 3.2 (2026), 7-19. Print. doi:10.5455/JPPR.20251229122615

APA (American Psychological Association) Style

Guermit, M. & Aribi, . M. M. (2026) Rapamycin: From Microbial Discovery to Therapeutic Innovations — Advances, Challenges, and Future Prospects. Journal of Pharmacological and Pharmaceutical Research, 3 (2), 7-19. doi:10.5455/JPPR.20251229122615