Synonyms: 40-O-(2-((1-(32-(4-amino-3-(2-aminobenzo[d]oxazol-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-27-oxo-3,6,9,12,15,18,21,24-octaoxa-28-azadotriacontyl)-1H-1,2,3-triazol-4-yl)methoxy)ethyl)-rapamycin
Compound class:
Synthetic organic
Comment: RapaLink-1 is a new-generation bivalent (bitopic) mTOR inhibitor, comprising a rapamycin-FRB-binding element (sirolimus, a.k.a. rapamycin) linked to an ATP binding site competitive TORKi (sapanisertib, a.k.a. MLN0128) via a PEG linker [1]. RapaLink-1 is able to overcome resistance to TORKis of mutant mTOR proteins in vitro, inhibiting proliferation MCF-7 cells at levels comparable to rapamycin or a combination of rapamycin and MLN0128.
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References |
1. Rodrik-Outmezguine VS, Okaniwa M, Yao Z, Novotny CJ, McWhirter C, Banaji A, Won H, Wong W, Berger M, de Stanchina E et al.. (2016)
Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature, 534 (7606): 272-6. [PMID:27279227] |