AZD1208 efficacy and pharmacokinetic (PK)-PD analyses in AML xenograft models. (A) CB17 SCID mice implanted subcutaneously with MOLM-16 cells were treated once daily (QD) with either vehicle or AZD1208 by oral gavage for 14 days to assess effect on tumor growth. Data shown are the average ± standard error of the mean (SEM). **Significant difference in tumor size at day 25 between vehicle- and AZD1208-treated mice; Student t test P < .001. (B) Immunoblot analysis of MOLM-16 tumors from mice treated with 30 mg/kg AZD1208 at the times shown. (C) pBAD levels as percent of vehicle-treated controls measured at the indicated times and doses, as described in “Methods.” Data represent the average of triplicates + SEM. (D) Percent pBAD inhibition at multiple plasma drug levels was measured to determine the PK-PD relationship and concentration required for 50% inhibition. Data are from the study in (C) and an additional data set including 18-hour time points. The graph was generated by using Phoenix WinNonlin 6.3 software (Pharsight). (E) CB17 SCID mice implanted subcutaneously with KG-1a cells were treated once daily with vehicle or AZD1208 by oral gavage or twice per week, on consecutive days, with cytarabine by intraperitoneal injection from day 14 to day 39 postimplantation. Data shown are the average ± SEM. **Significant difference in tumor size at days 39 and 50 between AZD1208-treated or cytarabine-treated mice and mice treated with the combination of AZD1208 and cytarabine. Student t test P < .001.