KY-05009

KY-05009 is an ATP-competitive Traf2- and Nck-interacting kinase (TNIK) inhibitor with a Ki 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[1].

Signaling Pathways >> MAPK/ERK Pathway >> MAP4K

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Stem Cell/Wnt >> Wnt

TNIK:100 nM (Ki)

KY-05009 (0.1-30 μM; 24 hours; RPMI8226 cells) treatment inhibits the proliferation of RPMI8226 cells in a dose-dependent manner[1]. KY-05009 (1-3 μM; 48-72 hours; RPMI8226 cells) treatment induces caspase-dependent apoptosis in RPMI8226 cells in a dose-dependent manner[1]. KY-05009 (3 μM; 1 hour; RPMI8226 cells) treatment suppresses the transcriptional activity of Wnt signaling-related genes, including TNIK, CTNNB1, TCF7, and TCF4[1]. .KY-05009 (3 μM; 9 hours; RPMI8226 cells) treatment inhibits the IL-6-induced interaction between TCF4 and β-catenin and the phosphorylation of TCF4[1]. Cell Proliferation Assay[1] Cell Line: RPMI8226 cells Concentration: 0.1 μM, 0.3 μM, 1 μM, 3 μM, 10 μM, 30 μM Incubation Time: 24 hours Result: Inhibited the proliferation of RPMI8226 cells. Apoptosis Analysis[1] Cell Line: RPMI8226 cells Concentration: 1 μM, 3 μM, 10 μM Incubation Time: 48 hours, 72 hours Result: Induced the binding of fluorescent Annexin V and 7-amino-actinomycin D (7-AAD) uptake. RT-PCR[1] Cell Line: RPMI8226 cells Concentration: 3 μM Incubation Time: 1 hour Result: Suppressed the transcriptional activity of Wnt signaling-related genes, including TNIK, CTNNB1, TCF7, and TCF4. Western Blot Analysis[1] Cell Line: RPMI8226 cells Concentration: 3 μM Incubation Time: 9 hours Result: The IL-6-induced interaction between TCF4 and β-catenin and the phosphorylation of TCF4 were inhibited.

[1]. Lee Y, et al. Synergistic inhibition effect of TNIK inhibitor KY-05009 and receptor tyrosine kinase inhibitor dovitinib on IL-6-induced proliferation and Wnt signaling pathway in human multiple myeloma cells. Oncotarget. 2017 Jun 20;8(25):41091-41101.