Inhibitor of Traf2- and Nck-Interacting Kinase (TNIK; Ki value 100 nM in ATP competitive assay) that attenuates TGF-β1-mediated Wnt and Smad signaling and epithelial-to-mesenchymal transition (EMT) in human lung adenocarcinoma A549 cells. Additionally, KY05009 inhibits TGF-β1-induced phosphorylation of JNK1/2, FAK, Src, and paxillin.
Serine/threonine kinase Traf2- and Nck-interacting kinase (TNIK) is a member of the germinal center kinase family that has been identified as an anti-cancer target molecule to regulate the Wnt signaling pathway. KY 05009 is a potent TNIK inhibitor with an IC50 value of 9nM. It also shows inhibitory activity against MLK1 with an IC50 value of 18nM. In serum-deprived A549 cells, incubation with KY05009 (1-10µM) for 48 h significantly inhibited TGF-β1-induced activation of the Wnt signaling pathway, but did not lead to significant cytotoxicity up to 10µM. Also in A549 cells, KY05009 at 10µM significantly inhibited TGF-β1-induced Smad2 phosphorylation and the nuclear translocation of p-Smad and Smad2/3. TGF-β1-induced migration and invasion of A549 cells were significantly inhibited by KY-05009 at 10µM[3].
作用机制
KY 05009 is a TNIK inhibitor that shows a high affinity for the ATP binding site in TNIK (Ki=100nM). There are two hydrogen bonds between KY 05009 and the Cys108 in the hinge region of TNIK. KY 05009 also has CH/π interactions with Val31, Gly111, and Leu160[3].
搜索
