NG-25

Description: NG25 is a novel, potent and synthesized dual TAK1 (TGFbeta-activated kinase 1) and MAP4K2 (mitogen-activated protein kinase kinase kinase kinase 2) inhibitor, with IC50s of 149 nM and 21.7 nM, respectively. TGFbeta-activated kinase-1 (TAK1) is a key intracellular molecule participating in genotoxic stresses-induced NF-kappaB activation. Targeting TAK1 as a strategy to enhance cancer treatment efficacy has been studied in several malignancies. NG25 greatly enhanced Dox treatment efficacy in a panel of breast cancer cell lines. In this pre-clinical study, NG25 partially blocked Dox-induced p38 phosphorylation and IkappaBalpha degradation and enhanced Dox-induced cytotoxic effects and apoptosis in all breast cancer cell lines tested. Taken together, we provided clear evidence that NG25 sensitizes the breast cancer cells to Dox treatment in vitro. This combination may be an effective and feasible therapeutic option maximizing Dox efficacy and meanwhile minimizing Dox side effects in treating breast cancer.

References: Sci Rep. 2016 Sep 7; 6:32737; J Med Chem. 2015 Jan 8; 58(1):183-96.