Rapalink-1
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| Formula | C91H138N12O24 |
| Molar mass | 1784.165 g·mol−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
- ^ Lee BJ, Boyer JA, Burnett GL, Thottumkara AP, Tibrewal N, Wilson SL, et al. (October 2021). "Selective inhibitors of mTORC1 activate 4EBP1 and suppress tumor growth". Nature Chemical Biology. 17 (10): 1065–1074. doi:10.1038/s41589-021-00813-7. PMC 9249104. PMID 34168367.
- ^ a b Burnett GL, Yang YC, Aggen JB, Pitzen J, Gliedt MK, Semko CM, et al. (January 2023). "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. doi:10.1021/acs.jmedchem.2c01658. PMC 9841523. PMID 36533617.
- ^ Wang N, Zhou K, Liang Z, Sun R, Tang H, Yang Z, et al. (December 2023). "RapaLink-1 outperforms rapamycin in alleviating allogeneic graft rejection by inhibiting the mTORC1-4E-BP1 pathway in mice". International Immunopharmacology. 125 (Pt B) 111172. doi:10.1016/j.intimp.2023.111172. PMID 37951193.
- ^ Kumar J, Ng K, Rallis C (September 2025). "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) 1364. doi:10.1038/s42003-025-08731-3. PMC 12479844. PMID 41023123.