NG 25 is a type II kinase inhibitor that inhibits MAP4K2 and TAK1 (IC50s = 21.7 and 149 nM, respectively).1 It also inhibits the Src family kinases Src and LYN (IC50s = 113 and 12.9 nM, respectively) and Abl family kinases (IC50s = 75.2 nM), as well as CSK, FER, and p38α (IC50s = 56.4, 82.3, and 102 nM, respectively). NG 25 (100 nM) prevents TNF-α-induced IKKα/β phosphorylation and IκB-α degradation in L929 cells. It inhibits secretion of IFN-α and IFN-β induced by CpG type B and CL097, respectively, in Gen2.2 cells in a concentration-dependent manner.2 NG 25 decreases cell viability of HCT116KRASWT, and to a greater degree of HCT116KRASG13D, colorectal cancer cells in a concentration-dependent manner.3 It also reduces tumor growth and increases the number of TUNEL-positive tumor cells in a CT26KRASG12D mouse orthotopic model of colorectal cancer.
References
1. Tan, L., Nomanbhoy, T., Gurbani, D., et al. Discovery of type II inhibitors of TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2). J. Med. Chem. 58(1), 183-196 (2015).
2. Pauls, E., Shpiro, N., Peggie, M., et al. Essential role for IKKβ in production of type 1 interferons by plasmacytoid dendritic cells. J. Biol. Chem. 287(23), 19216-19228 (2012).
3. Ma, Q., Gu, L., Liao, S., et al. NG25, a novel inhibitor of TAK1, suppresses KRAS-mutant colorectal cancer growth in vitro and in vivo. Apoptosis 24(1-2), 83-94 (2019).