mTOR inhibitor; Autophagy modulator. mTORC1 pathway members interact with SARS-CoV-2 N and Orf8 proteins. Gordon et al. bioRxiv, Mar 23 2020, https://doi.org/10.1101/2020.03.22.002386.
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- Applications:Approved drug (U.S.) that could be repurposed
Biochemicals & reagents
1) Kay, et al. (1991) Inhibition of T and B lymphocyte proliferation by rapamycin. Immunology 72 544 / 2) Mita, et al., (2003) The molecular target of rapamycin (mTOR) as a therapeutic target against cancer Cancer Biol. Ther. 2(4 Suppl 1), S169 / 3) Lamming, et al. ( 2012). Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science 335 1638 / 4) Sarkar et.al. (2009), Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies Cell Death and Differentiation 16, 46
Rapamycin is a clinically relevant immunosuppressant which inhibits the response to interleukin-2 blocking activation of T- and B-cells (1). This compound forms a complex with cytosolic FK-binding protein 12 (FKB12) that binds to mTOR Complex 1 (mTORC1) inhibiting the mammalian target of rapamycin (mTOR) (2), it also binds to mTORC2 leading to decreased glucose tolerance and insensitivity to insulin (3) and induces autophagy (4).