A subset of AML cell lines is sensitive to PIM kinase inhibitors. (A) Structures of 5 PIM kinase inhibitors representing 3 unique chemical scaffolds. (B) Schematic of the strategy employed to identify and molecularly characterize responders to PIM kinase inhibition. (C) The specified AML cell lines were treated with 3 diverse scaffolds of PIM kinase inhibitors at 8 concentrations (1:3 serial dilutions with maximal concentration of 3 µM). The distinctive sensitivity of a subset of AML cell lines to the impediment of PIM kinase activity is consistent across all 3 compounds tested, indicative of the on-target cellular response. (D) Summary of IC50 values of each PIM inhibitor used across responders and nonresponders.