FOXM1 INHIBITOR III FDI-6 (C15-1305-111)

General description

A cell-permeable thienopyridinylcarboxamide compound that selectively and directly binds to forkhead box M1 (FOXM1) in a 1:1 stoichiometry and reversibly blocks its DNA binding activity (IC₅₀ = 22.5 µM). Does not affect the transcriptional activity of FOXA1, FOXA2, FOXP2, and GATA1 in any significant manner. Shown to suppress the expression of FOXM1 target genes and block the proliferation of FOXM1 expressing breast cancer cells (GI₅₀ = 18 µM for MCF-7 and MDA-MB-231 cells and 21.8 µM for PEO-1 cells). Unlike thiostrepton (Cat. No. 598226), it displays minimal off-target effects and does not affect 20S proteasomal activity.

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

Biochem/physiol Actions

Cell permeable: yes

Primary Target
FOXM1

Warning

Toxicity: Standard Handling (A)

Reconstitution

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

Other Notes

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

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Molecular Weight: 437.43. Empirical Formula: C₁₉H₁₁F₄N₃OS₂. Assay: ≥. 98% (HPLC). Quality Level: 100. form: solid. manufacturer/tradename: Calbiochem^®. . storage condition: OK to freeze, protect from light. color: yellow. solubility: DMSO: 50 . mg/mL. storage temp.: 2-8°C. Storage Class Code: 11 - Combustible Solids. WGK: WGK 3. Flash Point(F): Not applicable. Flash Point(C): Not applicable.