Fig. 1: RapaLink-1 is a potent mTOR inhibitor that requires FKBP12 for its cellular activity.
From: Brain-restricted mTOR inhibition with binary pharmacology
a, Chemical structures of RapaLink-1 and FK506. b, Inhibition of mTOR activity by MLN128, RapaLink-1 or rapamycin in the presence or absence of 10 µM FKBP12 in the in vitro kinase assay (n = 2; data are plotted as individual points). c, K562 CRISPRi cells transduced with sgRNAs targeting GAL4-4 (control) or FKBP12 were treated with RapaLink-1 and cell proliferation was assessed after 72 h. In the last listed condition, cells were transduced with sgRNA but treated with RapaLink-1 in the presence of 10 µM FK506 (n = 3). Data are presented as mean ± s.d. d, Immunoblot analysis of mTOR signalling in MCF7 cells treated with DMSO, RapaLink-1, FK506 or a combination of RapaLink-1 and FK506. Results shown are representative of three independent experiments. Actin was the loading control. For gel source data, see Supplementary Fig. 1. MW, molecular weight. e, Schematics of the proposed working model. The grey circles indicate cellular membranes.
