a, MCF-7 cells were treated for 4 hours with either RapaLink-1 (10 nM) or rapamycin (10 nM) with simultaneous addition of increasing doses of either rapamycin or RapaLink-1 (left and right panels respectively). Immunoblot analyses were performed on mTOR effectors. b, Mice bearing RR1 or TKi-R (c) xenograft tumors were treated for 24 hours with a single dose of either vehicle, rapamycin (10 mg/kg), AZD8055 (75 mg/kg) or RapaLink-1 (1.5 mg/kg) (n=4 for each group). Immunoblot analyses were performed on mTOR effectors. d, MDA-MB-468 cells inducibly expressing mTOR WT were treated with either rapamycin, MLN0128, combination of rapamycin and MLN0128 or RapaLink-1 for 4 hours. Immunoblot analyses were performed on mTOR effectors with the indicated antibodies. Rapamycin and MLN0128 panels are the same shown for WT in Extended Data Figure 2c and e respectively.