Description: NG25 is a novel, potent and synthesized dual TAK1 (TGFβ-activated kinase 1) and MAP4K2 (mitogen-activated protein kinase kinase kinase kinase 2) inhibitor, with IC50s of 149 nM and 21.7 nM, respectively. The important intracellular molecule TGFβ-activated kinase-1 (TAK1) is involved in the activation of NF-κB caused by genotoxic stress. A number of malignancies have been studied to determine the effectiveness of treatment when TAK1 is targeted. A panel of breast cancer cell lines treated with Dox and NG25 showed significantly improved therapeutic efficacy. In this pre-clinical study, NG25 increased Dox-induced cytotoxicity and apoptosis in all tested breast cancer cell lines while enhancing Dox-induced p38 phosphorylation and I-B degradation in some cases. Together, our findings demonstrated conclusively that NG25 sensitizes breast cancer cells to Dox treatment in vitro. This combination may be a viable and effective therapeutic option for treating breast cancer by increasing Dox efficacy while minimizing Dox side effects.