M606 is a selective, iron-chelating small molecule inhibitor of MYCN/c-Myc, reduces MYCN protein expression by acting on the MYCN promoter via E2F3-mediated transcription factor binding sites.
M606 reduced MYCN mRNA levels in the MYCN-amplified human neuroblastoma cell line BE(2)-C in a time-dependent manner.
M606 reduced MYCN protein levels in BE(2)-C cells and c-MYC protein levels in the human hepatoblastoma cell line, HepG2, in a dose- and time-dependent manner.
M606 (2.5-25 uM) inhibits cell proliferation in MYC-expressing cell line SHR6-17.
M606 (1-5 uM) reduces clonogenic capacity in clonogenic assays on MYCN-amplified BE(2)-C and LAN-1 neuroblastoma cells.
M606 is cytotoxic in a panel of MYCN expressing (BE(2)-C, KELLY, IMR-32, LAN-1, NBL-WN) and c-MYC expressing (NBL-S, SY-5Y, SH-EP) neuroblastoma cell lines, but less cytotoxic to the nonmalignant fibroblast cell lines MRC5 and HSF.
M606 (25 mg/kg) inhibits tumor formation in the TH-MYCN transgenic mouse model of neuroblastoma.
M606 decreases MYC-mediated transcription in HepG2 cells but also a dramatic dose-dependent increase in HIF1A.
M606 is an iron chelator that modulates glucose metabolism, inhibits TCA cycle activity in neuroblastoma cells.
M606 mediates downregulation of MYCN via transcription factor E2F3, acts on the MYCN promoter via E2F3-mediated binding sites to reduce MYCN protein expression.