FDI-6 is an inhibitor of FOXM1. FDI-6 binds directly to FOXM1 protein, to displace FOXM1 from genomic targets in MCF-7 breast cancer cells, and induce concomitant transcriptional down-regulation.
FDI-6 is characterized in depth and is shown to bind directly to FOXM1 protein, to displace FOXM1 from genomic targets in MCF-7 breast cancer cells, and induce concomitant transcriptional down-regulation. MDA-MB-231 ER-negative breast and PEO-1 ovarian cancer cells are sensitive to FDI-6 in cell viability assays (GI50=21.8 μM and 18.1 μM, respectively) and exhibit comparable down-regulation of CDC25B after a 3 h treatment with FDI-6. The transcription factor FOXM1 regulates a network of proliferation-associated genes critical to mitotic spindle assembly, chromosome segregation, and G2/M transition, with depletion leading to cell cycle arrest. Importantly, aberrant up-regulation of FOXM1 has been shown to be a key driver of cancer progression and has been proposed as an initiating factor of oncogenesis[1].
[1]. Gormally MV, et al. Suppression of the FOXM1 transcriptional programme via novel small molecule inhibition. Nat Commun. 2014 Nov 12;5:5165.