HLM006474 is a non-selective inhibitor of the transcription factor E2F (IC50 = 29.8 μM for E2F4). It inhibits DNA binding to E2F1, E2F2, and E2F4 in A375 melanoma cells when used at a concentration of 40 μM. HLM006474 (40 μM) decreases protein levels of E2F4 and cyclin D3 and induces apoptosis in A375 cells. It also induces apoptosis in MDA-MB-231, but not MCF-7, cells and inhibits the growth of cancer cells in a panel of 17 lung cancer cell lines (IC50s = 15.5-75.1 μM). HLM006474 reduces tumor growth in retinoblastoma-prone Chx10Cre;Rbfl/fl;p107-/- mice and in an A375 mouse xenograft model when administered at a dose of 100 mg/kg and 2 mg per mouse, respectively.
