Rapalink-1 |
Catalog No.GC11607 |
RapaLink-1, el inhibidor mTOR bivalente de tercera generaciÓn, combina rapamicina con MLN0128 mediante un enlazador quÍmico inerte. RapaLink-1 muestra una mejor eficacia que la rapamicina o los inhibidores de la quinasa mTOR (TORKi), bloqueando potentemente los mutantes activadores de mTOR derivados del cÁncer. RapaLink-1 puede cruzar la barrera hematoencefÁlica. La uniÓn de RapaLink-1 a FKBP12 da como resultado una inhibiciÓn especÍfica y duradera de mTORC1. RapaLink-1 desempeÑa un papel antitrombÓtico en el sÍndrome antifosfolÍpido al mejorar la autofagia. Actividad anticancerÍgena.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1887095-82-0
Sample solution is provided at 25 µL, 10mM.
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.
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