ArticlePloS one2014
A novel aminothiazole KY-05009 with potential to inhibit Traf2- and Nck-interacting kinase (TNIK) attenuates TGF-β1-mediated epithelial-to-mesenchymal transition in human lung adenocarcinoma A549 cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models.Nature biotechnology · 2025Trial
- De Novo Discovery of Nonstandard Thioisoindole-Bridged Bicyclic Peptides Targeting Traf2- and NCK-Interacting Kinase.Angewandte Chemie (International ed. in English) · 2026Article
- TRAF2 and NCK interacting kinase: a novel regulator of integrin αResearch and practice in thrombosis and haemostasis · 2025Article
- TNIK: A redox sensor in endothelial cell permeability.Science advances · 2024Article
- TNIK in disease: from molecular insights to therapeutic prospects.Apoptosis : an international journal on programmed cell death · 2024Review
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- MiR-5590-3p inhibits the proliferation and invasion of ovarian cancer cells through mediating the Wnt/β-catenin signaling pathway by targeting TNIK.Histology and histopathology · 2024Article
- Article
- De Novo Discovery of Thiopeptide Pseudo-natural Products Acting as Potent and Selective TNIK Kinase Inhibitors.Journal of the American Chemical Society · 2022Article
- Structural Insight into TNIK Inhibition.International journal of molecular sciences · 2022Review
- Computational study on new natural compound inhibitors of Traf2 and Nck-interacting kinase (TNIK).Aging · 2022Article
- Combination Effect of Cilengitide with Erlotinib on TGF-β1-Induced Epithelial-to-Mesenchymal Transition in Human Non-Small Cell Lung Cancer Cells.International journal of molecular sciences · 2022Article
- Phosphorylation-dependent control of Activity-regulated cytoskeleton-associated protein (Arc) protein by TNIK.Journal of neurochemistry · 2021Article
- Development and therapeutic potential of 2-aminothiazole derivatives in anticancer drug discovery.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2021Review
- Article
- Characterization of the ERG-regulated Kinome in Prostate Cancer Identifies TNIK as a Potential Therapeutic Target.Neoplasia (New York, N.Y.) · 2019Article
- The role of contextual signal TGF-β1 inducer of epithelial mesenchymal transition in metastatic lung adenocarcinoma patients with brain metastases: an update on its pathological significance and therapeutic potential.Contemporary oncology (Poznan, Poland) · 2019Review
- miR-145-5p inhibits epithelial-mesenchymal transition via the JNK signaling pathway by targeting MAP3K1 in non-small cell lung cancer cells.Oncology letters · 2017Article
- Article
- TNIK inhibition abrogates colorectal cancer stemness.Nature communications · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor (TGF)-β triggers the epithelial-to-mesenchymal transition (EMT) of cancer cells via well-orchestrated crosstalk between Smad and non-Smad signaling pathways, including Wnt/β-catenin. Since EMT-induced motility and invasion play a critical role in cancer metastasis, EMT-related molecules are emerging as novel targets of anti-cancer therapies. Traf2- and Nck-interacting kinase (TNIK) has recently been considered as a first-in-class anti-cancer target molecule to regulate Wnt signaling pathway, but pharmacologic inhibition of its EMT activity has not yet been studied. Here, using 5-(4-methylbenzamido)-2-(phenylamino)thiazole-4-carboxamide (KY-05009) with TNIK-inhibitory activity, its efficacy to inhibit EMT in cancer cells was validated. The molecular docking/binding study revealed the binding of KY-05009 in the hinge region of TNIK, and the inhibitory activity of KY-05009 against TNIK was confirmed by an ATP competition assay (Ki, 100 nM). In A549 cells, KY-05009 significantly and strongly inhibited the TGF-β-activated EMT through the attenuation of Smad and non-Smad signaling pathways, including the Wnt, NF-κB, FAK-Src-paxillin-related focal adhesion, and MAP kinases (ERK and JNK) signaling pathways. Continuing efforts to identify and validate potential therapeutic targets associated with EMT, such as TNIK, provide new and improved therapies for treating and/or preventing EMT-based disorders, such as cancer metastasis and fibrosis.
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Registered trials
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