Fig. 4: Co-treatment with RapaLink-1 and RapaBlock allows brain-specific inhibition of mTOR.
From: Brain-restricted mTOR inhibition with binary pharmacology
a, Analysis of mTOR signalling in mouse whole brain and skeletal muscle after a single dose of RapaLink-1 (1 mg per kg), RapaBlock (40 mg per kg) or a combination of both. Quantified intensities are shown below each immunoblot as the fold increase relative to muscle or brain without insulin stimulation, normalized to GAPDH (n = 3; data are presented as mean ± s.d.). Statistical tests were performed between RapaLink-1 and RapaLink-1 + RapaBlock treatment groups at each time point (two-tailed unpaired Student’s t-test). Immunoblot images are shown for one animal from each group. See Extended Data Fig. 5 for other replicates. All samples are derived from the same experiment. Gels and blots were processed in parallel. GAPDH was the loading control. For gel source data, see Supplementary Fig. 1. b, Mice (n = 7) bearing luciferase-expressing orthotopic glioblastoma xenografts (U87MG) were treated intraperitoneally every 5 days with: (1) vehicle; (2) RapaBlock (40 mg per kg); (3) RapaLink-1 (1 mg per kg); and (4) RapaLink-1 (1 mg per kg) and RapaBlock (40 mg per kg). Tumour size and mouse weight were monitored every 5 days using bioluminescence imaging. Data are presented as mean ± s.d. Statistical tests were performed for each treatment group versus vehicle-treated group: two-tailed unpaired Student’s t-test (tumour size on day 20), and log-rank test (survival). c, Mice (n = 5) bearing luciferase-expressing orthotopic glioblastoma xenografts (GBM43) were treated intraperitoneally every 5 days with: (1) vehicle; (2) RapaBlock (60 mg per kg); (3) RapaLink-1 (1.2 mg per kg); and (4) RapaLink-1 (1.2 mg per kg) and RapaBlock (60 mg per kg). Tumour size and mouse weight were monitored every 3 days using bioluminescence imaging. Data are presented as mean ± s.d. Statistical tests were performed for each treatment group versus vehicle-treated group: two-tailed unpaired Student’s t-test (tumour size on day 10), and log-rank test (survival). NS, not significant.
