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Rapalink-1

Catalog No.
A8764
third-generation mTOR inhibitor
Grouped product items
SizePriceStock Qty
5mg
$700.00
In stock
25mg
$2,000.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

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.

Product Citation

Chemical Properties

StorageStore at -20°C
M.Wt1784.14
FormulaC91H138N12O24
Solubility≥178.4 mg/mL in DMSO; insoluble in H2O; ≥24.85 mg/mL in EtOH
SDFDownload SDF
Canonical SMILESO=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 ConditionShip with blue ice, or upon other requests.
General tipsFor 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.

Protocol

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

Chemical structure

Rapalink-1

Related Biological Data

Rapalink-1

Related Biological Data

Rapalink-1

Related Biological Data

Rapalink-1

Related Biological Data

Rapalink-1

Related Biological Data

Rapalink-1