MTOR and acute myeloid leukemia: One of the first compounds of this type to be developed was PI-103 (Figure 3), which provided proof-of-concept for the therapeutic potential of double PI3K/mTOR agents on AML cells by inhibiting leukemic proliferation, clonogenicity of leukemic progenitors, and inducing mitochondrial apoptosis [47] but did not enter clinical trials due to limited solubility and extensive metabolism [48].