a, Model of mTOR kinase (gray, constructed from structural models of PDB IDs 4JT5 and 1FAP). FKBP12 (green), FRB (cyan) and kinase (orange) domains are indicated. Inhibitors bound in the kinase active site and the FRB site are also shown (blue and red spheres, respectively). Shortest distance between rapamycin and MLN0128 inhibitors is indicated. b, Chemical structures of mTOR inhibitors binding in the active site (MLN0128, blue) and the FRB-site (rapamycin, red). c, Chemical structure of the bivalent mTOR inhibitor RapaLink-1.