| Identification | Back Directory | [Name]
RapaLink-1 | [CAS]
1887095-82-0 | [Synonyms]
RapaLink-1 RAPALINK 1;RAPALINK1 Rapamycin, 42-O-[2-[[1-[32-[4-amino-3-(2-amino-5-benzoxazolyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-27-oxo-3,6,9,12,15,18,21,24-octaoxa-28-azadotriacont-1-yl]-1H-1,2,3-triazol-4-yl]methoxy]ethyl]- | [Molecular Formula]
C91H138N12O24 | [MDL Number]
MFCD32708498 | [MOL File]
1887095-82-0.mol | [Molecular Weight]
1784.17 |
| Chemical Properties | Back Directory | [density ]
1.30±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
≥ 178.4mg/mL in DMSO | [form ]
Solid | [pka]
10.40±0.70(Predicted) | [color ]
White to light yellow |
| Hazard Information | Back Directory | [Uses]
RapaLink-1, the third-generation bivalent mTOR inhibitor, combines Rapamycin (HY-10219) with MLN0128 (HY-13328, a second-generation mTOR kinase inhibitor) by an inert chemical linker. RapaLink-1 shows better efficacy than Rapamycin or mTOR kinase inhibitors (TORKi), potently blocking cancer-derived, activating mutants of mTOR. RapaLink-1 can cross the blood-brain barrier. RapaLink-1 binding to FKBP12 results in targeted and durable inhibition of mTORC1. RapaLink-1 plays an antithrombotic role in antiphospholipid syndrome by improving autophagy. Anticancer activity[1][2]. | [in vivo]
RapaLink-1 (i.p.; every 5 days for 25 days, then once a week for 11 week) shows potent anti-tumor efficacy[1]. | Animal Model: | BALB/ Cnu/nu mice bearing U87MG intracranial xenografts[1] | | Dosage: | 1.5 mg/kg | | Administration: | I.p.; every 5 days for 25 days, then once a week for 11 week | | Result: | Led to initial regression and subsequent stabilization of tumor size.
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| [IC 50]
mTOR | [References]
[1] Fan Q, et al. A Kinase Inhibitor Targeted to mTORC1 Drives Regression in Glioblastoma. Cancer Cell. 2017 Mar 13;31(3):424-435. DOI:10.1016/j.ccell.2017.01.014 [2] Kuroshima K, et al. Potential new therapy of Rapalink-1, a new generation mammalian target of rapamycin inhibitor, against SU 11248-resistant renal cell carcinoma. Cancer Sci. 2020 May;111(5):1607-1618. DOI:10.1111/cas.14395 [3] Rodrik-Outmezguine VS, et al. Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature. 2016 Jun 9;534(7606):272-6. DOI:10.1038/nature17963 [4] Mu F, et al. RapaLink-1 plays an antithrombotic role in antiphospholipid syndrome by improving autophagy both in vivo and vitro. Biochem Biophys Res Commun. 2020 Apr 30;525(2):384-391. DOI:10.1016/j.bbrc.2020.02.084 |
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