Figure 4
Pracinostat combined with pacritinib is efficacious and synergistic in vivo in two different models of human AML. Female SCID-beige mice (n=12 per group) were inoculated with 5 × 106 SET-2 cells and treatment was started on d33 post-implantation (a, b). For the combination group, both pacritinib (SB1518) and pracinostat (SB939) were administered in half the volume (as a 20 mg/kg solution) every other day; when both compounds were given simultaneously, all other doses were given at 10 mg/kg, at least 8 h apart for 19 days (d0–d18). There was one non-treatment-related death in the vehicle group on study d11 (gavaging error). Female SCID mice (n=12 per group) were inoculated with 5 × 106 Molm-13 cells (c, d). Treatment was started on d11, animals were dosed every other day for 8 days, in contrast to (a), animals were dosed with pacritinib only daily (in the evenings), pracinostat dosing remained unchanged, all dosing was done in a 10 mg/kg solution. On the last day, mice were killed and excised tumors were weighed. The doses showing significant TGI versus vehicle (on the last day of the study) using analysis of variance/Dunnet’s post test, are indicated with **P<0.01 or ***P<0.001. (e) Tumors from the MOLM-13 efficacy study (c, d) were harvested on the last day 3 h post pacritinib dosing and immediately lysed. Western blot analyses for pFLT3, FLT3, pSTAT5 and β-actin are shown from the lysates of three randomly selected tumors from each treatment group of (c).
