Fig. 2

APG-2449 demonstrates antitumor activity and pharmacokinetic/pharmacodynamic correlation in ALK- or ROS1-positive xenografts in vivo. Antitumor activity of APG-2449 was evaluated in mice bearing subcutaneous tumors derived from H3122 NSCLC cells carrying EML4-ALK fusion gene (A; treated for 3 weeks, n = 7 per treatment group; T/C values were assessed on Day 21), KARPAS-299 cells carrying NPM-ALK fusion gene (B; treated for 3 weeks, n = 7 per treatment group; T/C values were assessed on Day 13), or Ba/F3 cells carrying CD74-ROS1 fusion gene (C; the control group was treated for 2 weeks and the other groups for 3 weeks, n = 5 per treatment group; T/C values were assessed on Day 15). D, Pharmacokinetics of APG-2449 in plasma (left panel) or tumors (right panel) of mice carrying KARPAS-299-derived CDX tissues (treated once, n = 3 per treatment group). E, Western blot analysis of ALK signaling pathway in tumors collected 24 hours after administration from the same experiment as shown in (D). Each lane represents a tumor collected from an individual animal. F, Western blot analysis of ROS1 signaling pathway in HCC78 cells carrying SLC34A2-ROS1 fusion following treatments in vitro. Dimethyl sulfoxide (DMSO) was included as a control. EML4, echinoderm microtubule-associated protein-like 4; NPM, nucleophosmin; SLC34A2, solute carrier family 34 member 2