AMZ30 is a selective, covalent inhibitors of protein phosphatase methylesterase-1(PME-1; IC50=600 nM); selectively inactivates PME-1 and reduces the demethylated form of PP2A in living cells. IC50 value: 600 nM Target: PME-1 inhibitor in vitro: AMZ30 showed substantially improved inhibition of PME-1 (IC50 value of 600 nM) with more than 100-fold selectivity relative to other SHs in human cell lysates. Incubation of HEK 293T cells with a concentration range of AMZ30 generated an in situ IC50 value for PME-1 inhibition of 3.5 μM as determined by gel-based ABPP without any observed cross-reactivity with other SHs even at 100 μM compound. Treatment of HEK 293T cells stably overexpressing PME-1 with 28 (20 μM) caused an ~80% reduction in the levels of demethylated PP2A .

• . Bachovchin DA, et al. Discovery and optimization of sulfonyl acrylonitriles as selective, covalent inhibitors of protein phosphatase methylesterase-1. J Med Chem. 2011 Jul 28;54(14):5229-36.  [Content Brief]