Animal experiment:

Tumor-bearing genetically-engineered mouse models (GEMMs) are monitored for onset of symptoms (breath distress) and then treated with JQEZ5 for three weeks (75 mg/kg IP daily). Tumors are visualized by MRI and tumor volume of the lungs is calculated using 3D Slicer. For xenograft experiments, H661 cells are dissociated into single cells, counted and resuspended at 2×106 cells per 250 μL of 1:1 media/matrigel. Eight- to 12-week-old female Foxn1nu/Foxn1nu mice are injected subcutaneously with 2×106 cells in two to three spots on the flanks. Tumors are allowed to grow to an approximate size of 200 mm3 (~10 weeks) and the mice are randomized for vehicle (n=3) or JQEZ5 administration (n=6, 75 mg/kg/d, i.p.) for 18 days. Tumor growth is measured by caliper measurements and tumor volume is calculated by standard methods[1].

JQEZ5 is a novel and potent EZH2 inhibitor.

Animals treated with JQEZ5 exhibit rapid and pronounced tumor regression over the three week treatment course. H3K27me3 levels are largely reduced with treatment further confirming the on-target effect of JQEZ5 in mice. The level of H3K27me3 is largely reduced with the treatment without effect on EZH2 levels in both the tumor and in the lung tissue of JQEZ5 treated animals[1].

References:
[1]. Zhang H, et al. Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer. Cancer Discov. 2016 Sep;6(9):1006-21.