SR18662, an optimized compund based on ML264 that inhibits Krüppel-like factor 5 (KLF5) with IC50 of 4.4 nM, reduces the viability of multiple colorectal cancer cell lines and induces apoptosis.

KLF5:4.4 nM

SR18662 significantly reduces growth and proliferation of CRC cells and shows improved efficacy in reducing viability of multiple CRC cell lines. Flow cytometry analysis following SR18662 treatment shows an increase in cells captured in either S or G2/M phases of the cell cycle and a significant increase in the number of apoptotic cells. SR18662 also reduces the expression of cyclins and components of WNT and MAPK signaling pathways.[1]

The effect of SR18662 treatment shows a significant dose-dependent inhibition of xenograft growth in mice and exceeds ML264 at equivalent doses. SR18662 is potential for colorectal cancer therapy.[1]

Cell lines: HT29, HCT116, DLD-1 and SW620 colorectal cancer cell lines. Concentrations: 0.001 μM-20 μM. Incubation Time: 24 h. Method: KLF5 promoter activity assay: DLD-1/pGL4.18hKLF5p cells are seeded in 96 well plate and treated with SR18662 dissolved in DMSO in the range of 0.001 to 20 μM or equivalent volume of DMSO as control for 24 h, the human KLF5 promoter activity is determined with the ONE-Glo luciferase assay system by a SpectramMax M3 plate reader.

Animal Models: 7-week-old male NuJ/Foxn1nu mice with DLD-1 human colorectal cells injected. Dosages: 5 mg/kg, 10 mg/kg, 25 mg/kg. Administration: I.P.