Momelotinib shows on-target therapeutic efficacy in a human AML xenograft model. (A) Tumor burden of NSG mice quantitated by whole-body bioluminescence imaging following IV injection of MOLM14-luc⁺ cells. Mice were randomly assigned to receive momelotinib (CYT) 100 mg/kg orally daily, 10 mg/kg orally daily, or vehicle control. Data are presented as mean ± standard error of the mean (n = 8/group). ***P = .0004 by unpaired Student t test. (B) Representative whole-body bioluminescent images of mice orthotopically xenografted with MOLM14-luc⁺ cells and treated with momelotinib (CYT; 100 mg/kg oral daily) or vehicle control. (C) Mice were euthanized 2 hours after the last treatment on day 28. Representative spleens from each treatment group are shown. (D) Protein extracts were made from spleens from each treatment group. Representative immunoblots from 2 spleens from each treatment group are shown. (E) Band intensity for immunoblots from all spleen samples were quantified by ImageJ. **P = .0059 by Welch t test. (F) mRNA was harvested from spleens from each treatment group, and c-MYC was quantitated by RT-PCR. *P = .0108 by Welch t test. (G) IKBKE expression (normalized to actin) was quantitated from the immunoblot in panel D using ImageJ.