The insulin-like growth factor receptor (IGF-IR) is a transmembrane protein, signaling via the tyrosine kinase domain of which is important for normal cell growth and differentiation. In addition, the IGF-IR stimulates mitogenesis and suppresses apoptosis of cancer cells. PQ401 is a potent inhibitor of IGF-IR signaling which inhibits autophosphorylation of IGF-IR with an IC50 less than 1 μM. PQ401 significantly reduced the proliferation of MCF-7 cells grown in serum with an IC50 of 8 μM. PQ401 also inhibited the growth of MCNeuA cells with an IC50 of 15 μM. PQ401 (15 μM; 24 h) induced caspase-mediated apoptosis. In vivo, PQ401 (50 or 100 mg/kg; i.p.; three times per week) resulted in a significant dose-dependent reduction in tumor growth in female mice model bearing MCNeuA tumor cells[3].
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