Pim inhibition suppresses MM growth in mouse xenograft model. (A) Scid/bg mice were administered a single oral dose of LGB321 at 10, 20, 50, and 100 mg/kg, and LGB321 levels were detected in plasma collected from each animal at 1, 8, and 24 hours post dose (n = 3 per time point). (B) Pharmacodynamics were measured by assessing modulation of p-BAD and p-S6RP in the lysate of subcutaneous KMS-11.luc tumors from animals given a single dose of 10, 20, 50, or 100 mg/kg of LGB321, at 1, 8, or 24 hours post dosing (n = 3 per time point). Both phosphorylated and total forms of BAD and S6RP were detected by electrochemiluminescence, and a ratio was calculated to express percent inhibition of the phosphorylated form normalized to vehicle-treated tumors. (C) Mice bearing subcutaneous KMS-11.luc tumors were dosed by oral gavage with vehicle or LGB321 at daily doses of 20, 40, or 100 mg/kg per day (n = 9 per group). A dose-dependent inhibition of tumor growth was demonstrated, and tumor stasis was achieved with 100 mg/kg per day. *P < .05. (D) Body weight of animals in all dosing groups was measured and calculated to express the changes within the period of study. SEM, standard error of the mean.