Figure 4
Pharmacodynamics versus pharmacokinetics of Narazaciclib in mouse models. Panel A/B/C demonstrate that Narazaciclib inhibited AML tumor growth in a dose-dependent manner: (A) inhibition of the tumor growth of a CSF1R driven Ba/F3-ETV6-CSF1R xenograft in immunodeficient mice; (B) reduction of the tumor burden of a FLT3-ITD-bearing AM7577 AML-PDX; C. anti-AML activities in a CSF1R highly expressing AM8096 AML-PDX (Tumor growth curves are shown as mean tumor volume ± standard error of the mean (SEM). Significance was calculated using two-way ANOVA with post-hoc comparisons between treatment groups and vehicle group. *, p < 0.05; **, p < 0.01; ***, p < 0.001). Panel D/E: Pharmacokinetic (PK) evaluation of narazaciclib in non-tumor bearing mice. (D) The plasma concentration-curves of narazaciclib following a single oral administration at 100 mg/kg or 30 mg/kg. (E) PK parameters after the single-dose administration of narazaciclib at 100 mg/kg or 30 mg/kg orally. T1/2, elimination half-life; Tmax, Time to peak drug concentration; Cmax, maximum concentration; AUC0-∞, area under the plasma concentration–time curve from zero to infinity; AUC0-t, area under the plasma concentration–time curve from zero to the time of the last quantifiable time-point; CL_F, total body clearance; Vz-F, total volume of distribution. All data are presented as mean tumor volume ± standard error of the mean (SEM) of three animals per group.
