NCB-0846 (NCB0846) is the first orally available, small-molecule TNIK inhibitor with IC50 of 21 nM.
NCB-0846 also weakly inhibits FLT3, JAK3, PDGFRα, TRKA, CDK2/CycA2, and HGK (IC80>0.1 uM).
NCB-0846 induces faster migration of TCF4 phosphorylated by TNIK at 0.1-0.3 uM, and completely inhibits at 3 uM; also reduces the expression of TNIK, AXIN2, cMYC, LRP6 and LRP5.
NCB-0846 abrogates colorectal cancer stemness, suppresses Wnt-driven intestinal tumorigenesis in Apc(min/+) mice.
