In this study, we demonstrated that ZN444B exerts its inhibitory effect on breast cancer by regulating the HDAC1-Sp1-FOSL2 axis mainly through the following ways (Fig. 8): (1) ZN444B binds to the deacetylase domain of HDAC1, blocks the interaction of HDAC1 and Sp1, and inhibits the deacetylase activity of HDAC1 on Sp1, subsequently increases the acetylation of Sp1 at K703. Here, FOSL2 is linked to breast cancer.