IC50: 6.4 nM (PME-1 in HEK293T), 4.2 nM (PME-1 in MDA-MB-231)

Three described PME-1 inhibitors are tested in this assay and a thermal shift with 100 μM ABL127 is detected. Using 25 or 50 μM ABL127 also shows a shift in protein melting temperature. It is found that treatment of Ishikawa cells with ABL127 and AMZ-30 significantly decreases cell proliferation similarly to depletion of PME-1 with shRNA. It is also found that treatment of ECC-1 cells with ABL127 or AMZ-30 affects cell invasion in a dose-dependent manner. The treatment of EC cells with ABL127 leads to a significant ~45 % increase in protein phosphatase 2A (PP2A) activity, while treatment with AMZ-30 leads to a modest ~10 % increase in PP2A activity.

No significant decrease in tumor burden can be assessed in these pilot studies. Gel-based profiles indicate that brain PME-1 is inactivated by ABL127, but overlapping serine hydrolase activities preclude a confident assessment of the extent of inactivation.