ATUX-3364 and ATUX-8385 affect PP2A enzyme activity. SK-N-AS, SK-N-BE(2), SH-EP, or WAC2 cells were treated with ATUX-3364 or ATUX-8385 for 24 h and PP2A activity measured. Percent PP2A enzyme activity was compared to that of untreated (control) cells. (A) PP2A activation was significantly increased in SK-N-AS with ATUX-3364 or ATUX-8385. Similarly, PP2A was significantly activated in the three other cell lines with both compounds. There was no significant difference in PP2A activation between the two compounds in any of the cell lines (B). In SK-N-AS cells, expression of CIP2A was decreased at higher doses and SET expression was unchanged following ATUX-3364 or ATUX-8385 treatment. (C) Expression of SET (left panel) was increased in SK-N-BE(2) cells and CIP2A decreased (right panel) after treatment. (D) Treatment with ATUX-3364 or ATUX-8385 led to decreased CIP2A expression but did not alter SET expression in SH-EP cells. (E) Treatment of WAC2 cells with ATUX-8385 decreased CIP2A and SET expression but ATUX-3364 increased these proteins at higher doses. (F) CIP2A expression was increased with the highest dose of ATUX-8385 but SET expression was variably affected in the NB PDX COA6 cells. Data reported as mean fold change ± standard error of the mean (SEM), and experiments were repeated with at least three biologic replicates. * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001. The uncropped bolts are shown in Supplementary Materials.