MAP4K7/TNIK
MAP4K7/TNIK is a TRAF2- and NCK-interacting serine/threonine kinase that functions as a regulatory component of the β-catenin-TCF4 transcriptional complex[1]. Mechanistically, TNIK activates Wnt target genes and supports full canonical Wnt/β-catenin transcriptional output[1][2]. In colorectal cancer, TNIK acts downstream of APC loss, making it relevant to APC-mutant Wnt-dependent tumor models[3]. TNIK inhibition suppressed colorectal cancer growth, cancer stemness, and Wnt-driven intestinal tumorigenesis in preclinical models[4]. Compared with related GCK-IV kinases, MAP4K4, MINK1/MAP4K6, and TNIK/MAP4K7 act redundantly in neuronal stress-induced DLK/JNK signaling, so isoform-selective interpretation requires careful experimental design[5]. For experimental applications, NCB-0846, mebendazole-derived OBD9, and ATP-site TNIK inhibitors provide tools to test Wnt transcription, colorectal cancer stemness, EMT, and inhibitor-binding mechanisms[4][6][7][8].
References:
- [1]. Mahmoudi T, et al. The kinase TNIK is an essential activator of Wnt target genes. EMBO J. 2009;28(21):3329-3340. [Content Brief]
- [2]. Shitashige M, et al. Traf2- and Nck-interacting kinase is essential for Wnt signaling and colorectal cancer growth. Cancer Res. 2010;70(12):5024-5033.
- [3]. Masuda M, et al. Therapeutic targets in the Wnt signaling pathway: Feasibility of targeting TNIK in colorectal cancer. Pharmacol Ther. 2015 Dec;156:1-9. [Content Brief]
- [4]. Masuda M, et al. TNIK inhibition abrogates colorectal cancer stemness. Nat Commun. 2016;7:12586. [Content Brief]
- [5]. Larhammar M, et al. The Ste20 Family Kinases MAP4K4, MINK1, and TNIK Converge to Regulate Stress-Induced JNK Signaling in Neurons. J Neurosci. 2017 Nov 15;37(46):11074-11084. [Content Brief]
- [6]. Yamada T, et al. Emergence of TNIK inhibitors in cancer therapeutics. Cancer Sci. 2017 May;108(5):818-823. [Content Brief]
- [7]. Zhou K, et al. Inhibition of Wnt Signaling in Colon Cancer Cells via an Oral Drug that Facilitates TNIK Degradation. Mol Cancer Ther. 2023 Jan 3;22(1):25-36. [Content Brief]
- [8]. Kukimoto-Niino M, et al. Structural Insight into TNIK Inhibition. Int J Mol Sci. 2022 Oct 27;23(21):13010. [Content Brief]
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MAP4K7/TNIK Related Products (6)
Related Products (6)
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DMX-5804
0 ImagesDMX-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.
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KY-05009
0 ImagesKY-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.
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MAP4K4-IN-7
0 ImagesCat. No.: HY-W402208CAS No.: 1499162-60-5MAP4K4-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.
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TNIK-IN-11
0 ImagesCat. No.: HY-183059TNIK-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.
