ME0328

ME0328 is an inhibitor of PARP-3 (IC50 = 0.89 μM) . ME0328 displays selectivity for PARP-3 over PARP-1, PARP-2 and other ARDT enzymes (IC50 values are 6.3, 10.8 and >30 μM respectively) . ME0328 also enhances CRISPR-Cas9-mediated HER2 mutation frequency, resulting in increased reduction in proliferation of HER2-positive breast cancer cells. (In Vitro) :ME0328 is a potent and selective inhibitor of ARTD3/PARP3 that is active in cells. In in vitro histone H1 modification assay, ME0328 inhibits the transferase activity of ARTD3 with an IC50 of 0.89±0.28 μM. In human A549 cells, ME0328 and ME0355 (at 10 μM) delay the resolution of γH2AX-containing foci that serve as markers for DNA double strand break repair following γ-irradiation (2 Gy) . In silico and in vitro physicochemical and metabolic profiling indicated that ME0328 is soluble, cell permeable, and metabolically stable in human liver microsomes and rat hepatocytes.