The Myc proto-oncogenes interact with Max to form a dimer that regulates gene transcription. The protein c-Myc, in particular, promotes gene expression relevant to cell growth and thus drives cancer. 10058-F4 is a cell-permeable thiazolidinone that inhibits the dimerization of c-Myc and Max at 64 μM, preventing c-Myc-dependent gene expression and cell proliferation. It induces cell cycle arrest, apoptosis, and myeloid differentiation at 100 μM in human acute myeloid leukemia cells. 10058-F4 is rapidly metabolized in mice when given intravenously, limiting its effects on tumors in vivo. In addition to c-Myc, 10058-F4 inhibits the nuclear Myc protein, N-Myc, at 50 μM, inducing arrest, apoptosis, and differentiation in neuroblastoma cells overexpressing the gene for N-Myc. This compound can be used to delineate novel actions of Myc proteins, especially those related to lipid and glucose metabolism.
