Chemistry:Rapalink-1
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Rapalink-1 is a drug which acts as an inhibitor of the enzyme mechanistic target of rapamycin (mTOR). It is a dimeric molecule consisting of rapamycin joined to a desalkyl derivative of sapanisertib by a linker group. Since both of these products inhibit mTOR but through action at distinct binding sites on the mTOR complex, it exhibits a dual mTOR inhibitory activity and has been suggested for applications as an anti-aging drug or for treatment of some forms of cancer.[1][2][3][4]
Rapalink-1 is synthesized using click chemistry, specifically through a copper-catalyzed azide-alkyne cycloaddition to join rapamycin and sapanisertib, an mTOR active-site inhibitor via a polyethylene glycol linker.[2]
References
- ↑ "Selective inhibitors of mTORC1 activate 4EBP1 and suppress tumor growth". Nature Chemical Biology 17 (10): 1065–1074. October 2021. doi:10.1038/s41589-021-00813-7. PMID 34168367.
- ↑ 2.0 2.1 "Discovery of RMC-5552, a Selective Bi-Steric Inhibitor of mTORC1, for the Treatment of mTORC1-Activated Tumors". Journal of Medicinal Chemistry 66 (1): 149–169. January 2023. doi:10.1021/acs.jmedchem.2c01658. PMID 36533617.
- ↑ "RapaLink-1 outperforms rapamycin in alleviating allogeneic graft rejection by inhibiting the mTORC1-4E-BP1 pathway in mice". International Immunopharmacology 125 (Pt B). December 2023. doi:10.1016/j.intimp.2023.111172. PMID 37951193.
- ↑ "Rapalink-1 reveals TOR-dependent genes and an agmatinergic axis-based metabolic feedback regulating TOR activity and lifespan in fission yeast". Communications Biology 8 (1). September 2025. doi:10.1038/s42003-025-08731-3. PMID 41023123.
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