NG 25 (hydrochloride hydrate)

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 HCT116^KRASWT, and to a greater degree of HCT116^KRASG13D, 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 CT26^KRASG12D mouse orthotopic model of colorectal cancer.

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 cellsJ. 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 vivoApoptosis24(1-2)83-94(2019)