Rapamycin across biology and medicine: From molecular mechanisms to clinical and translational frontiers.

Lyvia Neves Rebello Alves Nolasco, Eldamária de Vargas Wolfgramm Dos Santos, Raquel Silva Dos Reis Trabach, Débora Dummer Meira, Iúri Drumond Louro

Núcleo de Genética Humana e Molecular, Departamento de Ciências Biológicas, Universidade Federal do Espírito Santo (UFES), Vitória, Espírito Santo 29075-910, Brazil; Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Espírito Santo, Vitória, Espírito Santo 29047-105, Brazil. Electronic address: [email protected]úcleo de Genética Humana e Molecular, Departamento de Ciências Biológicas, Universidade Federal do Espírito Santo (UFES), Vitória, Espírito Santo 29075-910, Brazil; Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Espírito Santo, Vitória, Espírito Santo 29047-105, Brazil. Electronic address: [email protected]. · pubmed

Paper

Abstract

Rapamycin is a macrolide compound originally identified for its antifungal activity and subsequently recognized as a potent inhibitor of the mechanistic target of rapamycin (mTOR), a conserved signaling kinase that integrates nutrient availability, growth factor signals, and cellular stress responses to regulate cell growth and metabolism. This review examines rapamycin across biological and medical fields, covering its discovery, chemical and pharmacological properties, and the central role of mTOR as its primary molecular target. We summarize established and emerging clinical applications of rapamycin and its analogs, while critically addressing the limitations and adverse effects associated with mTOR inhibition. Furthermore, advances in translational research and future perspectives are also discussed. Collectively, current evidence supports mTOR inhibition as a unifying biological strategy for the prevention, treatment, and delayed onset of multiple chronic diseases, as well as for promoting healthspan. As the first clinically approved mTOR inhibitor, rapamycin has therefore become a foundational pharmacological tool for exploring the therapeutic potential of modulating the evolutionarily conserved mTOR signaling network across a broad spectrum of human diseases and age-related conditions.

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Research summary

Rapamycin, as an mTOR inhibitor, serves as a foundational pharmacological tool for promoting healthspan and delaying the onset of multiple chronic diseases. This is a comprehensive review of an established drug and its mechanism, providing a summary of existing knowledge rather than presenting novel experimental data or a breakthrough discovery, resulting in a solid but limited incremental impact on the field.

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