ABL127 is a selective and covalent inhibitor of protein methylesterase 1 (PME-1), with IC50 values of 6.4 nM and 4.2 nM in HEK293T and MDA-MB-231 cells, respectively.

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

In this study, three PME-1 inhibitor compounds were analyzed, demonstrating that ABL127, at concentrations of 100 μM, induces a thermal shift. Lower concentrations of ABL127 (25 or 50 μM) similarly affect protein melting temperature. The application of ABL127 and AMZ-30 on Ishikawa cells notably reduced cell proliferation, an effect comparable to PME-1 suppression via shRNA. Furthermore, treating ECC-1 cells with ABL127 or AMZ-30 impacted cell invasion in a dose-responsive manner. Specifically, ABL127 treatment on EC cells enhanced protein phosphatase 2A (PP2A) activity by approximately 45%, whereas AMZ-30 treatment resulted in a modest increase of around 10% in PP2A activity[1].

In these preliminary studies, no substantial reduction in tumor size was observed[1]. Moreover, gel analysis suggests that ABL127 deactivates the brain's PME-1 enzyme. However, due to the presence of similar serine hydrolase activities, accurately determining the degree of inactivation is challenging[2].