RapaLink-1

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].

Product Specifications

CAS Number

[1887095-82-0]

UNSPSC

12352005

Hazard Statement

H302, H315, H319, H335

Target

Autophagy; mTOR

Type

Reference compound

Related Pathways

Autophagy; PI3K/Akt/mTOR

Applications

Cancer-Kinase/protease

Field of Research

Cancer

Assay Protocol

https://www.medchemexpress.com/rapalink-1.html

Purity

99.65

Solubility

DMSO : ≥ 100 mg/mL|H2O : < 0.1 mg/mL

Smiles

NC1=C(C2=NC=N1)C(C3=CC=C(O4)C(N=C4N)=C3)=NN2CCCCNC(CCOCCOCCOCCOCCOCCOCCOCCOCCN(N=N5)C=C5COCCO[C@H](CC[C@H]6C[C@H]([C@@](CC([C@@H](/C=C([C@H]([C@H](C([C@@H](C[C@@H]7C)C)=O)OC)O)\C)C)=O)([H])OC([C@@](CCCC8)([H])N8C(C([C@@]9(O[C@@](C[C@@H](/C(C)=C/C=C/C=C/7)OC)([H])CC[C@H]9C)O)=O)=O)=O)C)[C@@H](C6)OC)=O

Molecular Formula

C91H138N12O24

Molecular Weight

1784.14

Precautions

H302, H315, H319, H335

References & Citations

[1]Fan Q, et al. A Kinase Inhibitor Targeted to mTORC1 Drives Regression in Glioblastoma. Cancer Cell. 2017 Mar 13;31 (3) :424-435.|[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.|[3]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.|[4]Rodrik-Outmezguine VS, et al. Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature. 2016 Jun 9;534 (7606) :272-6.