The natural product ADAADi (Active DNA-dependent ATPase A Domain inhibitor) inhibits the ATPase activity of the SWI2/SNF2 family of ATPases (88, 89). Enzymes from other families of DNA-dependent ATPases have no or greatly reduced sensitivity to ADAADi, and DNA-independent or RNA-dependent ATPases are not affected (88). ADAADi inhibits BRG1 nucleosome remodeling activity in vitro (88). We tested the ADAADi inhibitor on TNBC cell lines: MDA-MB-231, MDA-MB-468, and HDQ-P1. ADAADiN significantly decreased cell proliferation in these cell lines (85). However, ADAADi failed to decrease cell proliferation significantly in cells with experimentally reduced BRG1 expression. This observation strongly suggests that ADAADiN specifically targeted BRG1 in these cells by interfering with its ATPase function.
