NiCur blocks CBP HAT activity and downregulates p53 activation upon genotoxic stress. NiCur is a potent and selective inhibitor of CBP histone acetyltransferase (HAT) with an IC 50 value of 0.35 μΜ. NiCur can be used to perform mechanistic studies without affecting target proteins expression [1].

In U2OS cells, NiCur applied at concentrations of 0.5 to 1 μM significantly diminishes Dox-induced acetylation at lysine 382 on p53 (p53K382ac), phosphorylation at serine 15 on p53 (p53S15p), and overall p53 levels in a dose-dependent fashion. At a higher concentration of 1.5 μM, NiCur lowers acetylation at lysine 27 on histone H3 (H3K27ac) and restores cell proliferation in these cells. Moreover, in intestinal epithelial cells, NiCur suppresses Dox-induced activation of p53 without altering acetylation at serine 139 on histone H2A.X (H2A.X S139p). NiCur thus serves as a modulator of gene regulation by reprogramming the chromatin landscape, primarily by inhibiting CBP histone acetyltransferase (HAT) activity. Western Blot Analysis in U2OS cells corroborates these findings, showing a concentration-dependent reduction in p53K382ac, p53S15p, and p53 levels with NiCur treatment.