FOXM1 Inhibitor III, FDI-6

A cell-permeable thienopyridinylcarboxamide compound that targets forkhead box M1 (FOXM1) winged helix DNA-binding domain (DBD; aa 222-360 in FOXM1c) in a 1:1 stoichiometric ratio and effectively blocking FOXM1 DBD DNA-binding activity (IC₅₀ = 22.5 µM by EMSA; 15 nM DNA probe & 750 nM FOXM1 DBD) and displays antiproliferative activity in breast cancer cultures (GI₅₀ = 18 µM/MCF-7, 18.1 µM/PEO-1, and 21.8 µM/MDA-MB-231 with 72 h treatment). FDI-6 culture treatment reduces FOXM1 target genes promoter occupancy (by 36%/CDC25B and 38%/CCNB1 with 6 h treatment at 40 µM in MCF-7 cultures) and overall FOXM1 chromatin association (by 43%/20 µM and 79%/40 µM in MCF-7 cultures), resulting in decreased FOXM1 target genes mRNA level (by 57%/PLK1, 55%/CDC25B, 52%/AURKB, 45%/CARM1 with 6 h treatment at 40 µM in MCF-7 cultures). Close to a 19-fold enriched FOXM1 targets is seen among downregulated mRNA species when compared to those not affected by FDI-6 treatment, while little or no enrichment is seen pertaining to targets of highly homologous FOX family transcription factors FOXA1, FOXA2, and FOXP2 among mRNAs affected by FCI-6 treatment. Unlike Thiostrepton (Cat. No. 598226), FDI-6 does not inhibit 20S proteasome activity.

FOXM1 inhibitor FDI-6; NCGC00099374

Cell permeable: yes

Primary Target
FOXM1

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Gormally , M.V., et al. 2014. Nat. Commun.5, 5156.

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