Description
NG 25 is a type II kinase inhibitor that inhibits MAP4K2 and TAK1 (IC
50s = 21.7 and 149 nM, respectively). It also inhibits the Src family kinases Src and LYN (IC
50s = 113 and 12.9 nM, respectively) and Abl family kinases (IC
50s = 75.2 nM), as well as CSK, FER, and p38α (IC
50s = 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. NG 25 decreases cell viability of HCT116
KRASWT, and to a greater degree of HCT116
KRASG13D, colorectal cancer cells in a concentration-dependent manner. It also reduces tumor growth and increases the number of TUNEL-positive tumor cells in a CT26
KRASG12D mouse orthotopic model of colorectal cancer.
References
[1] LI TAN. Discovery of Type II Inhibitors of TGFβ-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2)[J]. Journal of Medicinal Chemistry, 2014, 58 1: 183-196. DOI:
10.1021/jm500480k[2] EDUARDO PAULS. Essential role for IKKβ in production of type 1 interferons by plasmacytoid dendritic cells.[J]. The Journal of Biological Chemistry, 2012, 287 23: 19216-19228. DOI:
10.1074/jbc.m112.345405[3] QIZHAO MA. NG25, a novel inhibitor of TAK1, suppresses KRAS-mutant colorectal cancer growth in vitro and in vivo[J]. Apoptosis, 2018, 24 1-2: 83-94. DOI:
10.1007/s10495-018-1498-z
