MAP4K7/TNIK Inhibitor

NCB-0846 is an orally active, selective inhibitor for Wnt, that inhibits Traf2- and Nck-interacting kinase (TNIK) with an IC₅₀ of 21 nM. NCB-0846 blocks TGF-β signaling pathway by inhibiting SMAD2/3 phosphorylation and nuclear translocation.

DMX-5804 is a potent, orally active and selective MAP4K4 inhibitor, with an IC₅₀ of 3 nM, a pIC₅₀ of 8.55 for human MAP4K4, less potent on MINK1/MAP4K6 (pIC₅₀, 8.18), and TNIK/MAP4K7 (pIC₅₀, 7.96). DMX-5804 enhances cardiomyocyte survival, and reduces ischemia-reperfusion injury in mice.

KY-05009 is an ATP-competitive Traf2- and Nck-interacting kinase (TNIK) inhibitor with a K_i of 100 nM. KY-05009 pharmacologically inhibits TGF-β1-induced epithelial-to-mesenchymal transition (EMT) in human lung adenocarcinoma cells. KY-05009 inhibits the protein expression of TNIK and transcriptional activity of Wnt target genes and induces apoptosis in cancer cells. KY-05009 exerts anti-cancer activity.

MAP4K4-IN-7 (Compound 8) is a MAP4K4 inhibitor. MAP4K4-IN-7 shows moderate inhibitory activity against TNIK, MAP4K4, and MINK1 with pIC₅₀ values of 6.8, 6.8, and 6.7 respectively. MAP4K4-IN-7 can be used for the researches of cancer and neurological disease, such as schizophrenia.

TNIK-IN-11 is a TNIK inhibitor with a human TNIK pIC₅₀ of 7.80. TNIK-IN-11 inhibits TNIK kinase activity and promotes neurite outgrowth. TNIK-IN-11 activates AKT signaling via increased phosphorylated AKT levels, and induces gene expression changes including upregulation of neuronal differentiation and morphological remodeling genes. TNIK-IN-11 can be used for the research of dup15q syndrome.