Rapalink-1

mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail

Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.

Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody

Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay

SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.

Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
RapaLink-1 is the third-generation mTOR inhibitor exploiting the unique juxtaposition of two drug (first- and second- generation mTOR kinase inhibitors) -binding pockets to create a bivalent interaction that allows inhibition of the mutants which has resistance to the previous TORKi (mTOR kinase inhibitors).
The PIK3CA-AKT-mTOR pathway is one of the most commonly activated pathways in human cancers, which has led to the development of small-molecule inhibitors that target various nodes in the pathway. Two generation of mTOR inhibitor had been developed.
Rapalink-1 is more potent than first- and second- generation mTOR inhibitors. RapaLink-1 could more potently reduce levels of both p-4EBP1 and cell proliferation. Researches compared rapamycin, RapaLink-1, and MLN0128 in LN229 and U87MG. Both growth inhibition and arrest in G0/G1 were more potent in response to RapaLink-1, compared with rapamycin or MLN0128. RapaLink-1 shows potent anti-tumor efficacy in vivo. RapaLink-1 led to initial regression and subsequent stabilization of tumor size in a xenograft model, while tumors treated with vehicle, rapamycin, or MLN0128 grew steadily.
RapaLink-1 could durably block mTORC1. RapaLink-1 is associated with FKBP12, an abundant mTOR-interacting protein, enabling accumulation of RapaLink-1. RapaLink-1 showed better efficacy than rapamycin or TORKi, potently blocking cancer-derived, activating mutants of mTOR.
References:
[1] Fan Q1, Aksoy O1, Wong RA1, 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] Rodrik-Outmezguine VS1, Okaniwa M2, Yao Z1, et al., Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature. 2016 Jun 9; 534 (7606): 272-6. doi: 10.1038/nature17963. Epub 2016 May 18.
- 1. Erin M O'Leary, Yufeng Tian, et al. "TGF-β Promotes Metabolic Reprogramming in Lung Fibroblasts via mTORC1-dependent ATF4 Activation." Am J Respir Cell Mol Biol. 2020 Nov;63(5):601-612. PMID:32668192
- 2. Kuroshima K, Yoshino H, et al. "Potential new therapy of Rapalink-1, a new generation mammalian target of rapamycin inhibitor, against sunitinib-resistant renal cell carcinoma." Cancer Sci. 2020;111(5):1607-1618. PMID:32232883
Storage | Store at -20°C |
M.Wt | 1784.14 |
Formula | C91H138N12O24 |
Solubility | ≥178.4 mg/mL in DMSO; insoluble in H2O; ≥24.85 mg/mL in EtOH |
SDF | Download SDF |
Canonical SMILES | O=C(NCCCCN1N=C(C2=CC=C(OC(N)=N3)C3=C2)C4=C(N)N=CN=C41)CCOCCOCCOCCOCCOCCOCCOCCOCCN5C=C(COCCO[[email protected]@H]6CC[[email protected]@H](C[[email protected]]([[email protected]@H](OC([[email protected]](CCCC7)N7C(C([[email protected]@]8(O)[[email protected]](C)CC[[email protected]](O8)C[[email protected]](OC)/C(C)=C/C=C/C=C/[[email protected]@H](C)C[[email protected]@H](C)C([[email protected]](OC)[[email protected]](O)/C(C)=C/[[email protected]]9C)=O)=O |
Shipping Condition | Ship with blue ice, or upon other requests. |
General tips | For obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. We do not recommend long-term storage for the solution, please use it up soon. |
Cell experiment:[1] | |
Cell lines |
Human glioma cell line U87MG |
Reaction Conditions |
0 ~ 200 nM Rapalink-1 for 3 days |
Applications |
In U87MG cells, both growth inhibition (0 ~ 200 nM Rapalink-1; 3 days) and arrest in G0/G1 (0 ~ 12.5 nM Rapalink-1; 48 hours) were more obvious in response to Rapalink-1, compared with Rapamycin or MLN0128. |
Animal experiment:[1] | |
Animal models |
BALB/Cnu/nu mice bearing U87MG intracranial xenografts |
Dosage form |
1.5 mg/kg Injected intraperitoneally (i.p.) every 5 or 7 days |
Applications |
Rapalink-1 led to initial regression and subsequent stabilization of tumor size, while tumors treated with vehicle, Rapamycin, or MLN0128 grew steadily. Furthermore, Rapalink-1 was well tolerated and associated with significantly improved survival. |
Note |
The technical data provided above is for reference only. |
References: 1. Fan Q, Aksoy O, Wong RA, et al. A kinase inhibitor targeted to mTORC1 drives regression in glioblastoma. Cancer Cell, 2017, 31(3): 424-435. |
Quality Control & MSDS
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Chemical structure

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