Figure 5. CHR-3996 is synergistic with Tosedostat (CHR-2797) in an in vivo model and causes rapid activation followed by down-regulation of NFκB signalling.

A. NOD/SCID IL2R^−/− mice were inoculated subcutaneously with 2×10⁶ H929 cells. Four days following the inoculation mice were administered CHR-3996, tosedostat, or a combination of the two agents on a daily basis. The tumours were measured every other day with callipers. The median tumour volume (calculated by 1/2(length)(width)²) is shown on the graph, Each treatment group n=10. B. and C. H929 cells were treated with tosedostat (CHR-2797) (APi) 1 μM, CHR-3996 (HDACi) 250 nM, or both compounds simultaneously and cytoplasmic/nuclear protein extracts prepared at the times indicated in the figure for B. immunoblotting and C. an NFκB DNA binding assay for p65 (i) and p52 (ii).