FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2042992682> ?p ?o ?g. }

• W2042992682 endingPage "B265" @default.
• W2042992682 startingPage "B265" @default.
• W2042992682 abstract "Abstract Introduction: Aberrant activation of Wnt pathway is a major force driving colorectal carcinogenesis, and therefore the Wnt pathway has been thought of as an attractive anticancer drug target. However, its complexity has made it difficult to find druggable targets in the Wnt pathway. Recently, we reported Traf2- and NCK-interacting kinase (TNIK) plays important roles in the Wnt signaling pathway by making a complex with beta-catenin and T-cell factor-4 (TCF4) in a nucleus. We also found that TNIK is activated in human colorectal cancer cell lines, and proliferations of those cells are highly dependent upon the expression and catalytic activity of TNIK. Therefore inhibitors of TNIK may represent a promising therapeutic approach for treating colorectal cancer. Here we describe a discovery and characterization of a novel TNIK inhibitor. Methods: To identify compounds that inhibit TNIK acitivity, we have produced a recombinant catalytic domain of human TNIK, and developed a high throughput screening (HTS) assay system using a peptide substrate. TCF/LEF reporter gene assay using HEK293 was established to validate hit compounds. To study the effects of TNIK inhbitors on the Wnt signal pathway, Wnt target genes were analyzed by RT-PCR and Western blotting. The selected compounds were subjected to a kinase selectivity panel assay. Results: By performing a high throughput screening campaigns of our 10K kinase-focused compound library against a recombinant human TNIK, we identified a series of novel thiazole compounds as a potent inhibitor of TNIK. Hit compound, NCB-0001 exhibited potent inhibitory activity for TNIK with an IC50 value of 8.6 nM. After subsequent optimization, N1662 was identified as a lead compound having a strong anti-proliferative activity in colorectal cancer cell lines. N1662 inhibited tumor growth in a mouse xenograft model of colorectal cancer. Further optimization led to compound N5355 that showed good TNIK enzyme inhibition and potent Wnt signal inhibition in the TCF reporter gene assay, as well as down-regulation of Wnt target genes. N5355 showed excellent kinase selectivity against a panel of 311 kinases. Detailed results will be presented in the conference. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B265. Citation Format: Yuko Uno, Hideki Moriyama, Shigeki Kashimoto, Yusuke Kawase, Miki Shitashige, Masaaki Sawa, Tesshi Yamada. Targeting Wnt signaling: Discovery and characterization of novel thiazole-based Traf2- and NCK-interacting kinase (TNIK) inhibitors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B265." @default.
• W2042992682 created "2016-06-24" @default.
• W2042992682 creator A5008176243 @default.
• W2042992682 creator A5011509062 @default.
• W2042992682 creator A5013711950 @default.
• W2042992682 creator A5018281596 @default.
• W2042992682 creator A5049388697 @default.
• W2042992682 creator A5060964643 @default.
• W2042992682 creator A5072194347 @default.
• W2042992682 date "2013-11-01" @default.
• W2042992682 modified "2023-09-25" @default.
• W2042992682 title "Abstract B265: Targeting Wnt signaling: Discovery and characterization of novel thiazole-based Traf2- and NCK-interacting kinase (TNIK) inhibitors." @default.
• W2042992682 doi "https://doi.org/10.1158/1535-7163.targ-13-b265" @default.
• W2042992682 hasPublicationYear "2013" @default.
• W2042992682 type Work @default.
• W2042992682 sameAs 2042992682 @default.
• W2042992682 citedByCount "2" @default.
• W2042992682 countsByYear W20429926822015 @default.
• W2042992682 countsByYear W20429926822022 @default.
• W2042992682 crossrefType "journal-article" @default.
• W2042992682 hasAuthorship W2042992682A5008176243 @default.
• W2042992682 hasAuthorship W2042992682A5011509062 @default.
• W2042992682 hasAuthorship W2042992682A5013711950 @default.
• W2042992682 hasAuthorship W2042992682A5018281596 @default.
• W2042992682 hasAuthorship W2042992682A5049388697 @default.
• W2042992682 hasAuthorship W2042992682A5060964643 @default.
• W2042992682 hasAuthorship W2042992682A5072194347 @default.
• W2042992682 hasConcept C104317684 @default.
• W2042992682 hasConcept C123233396 @default.
• W2042992682 hasConcept C137620995 @default.
• W2042992682 hasConcept C145059251 @default.
• W2042992682 hasConcept C170493617 @default.
• W2042992682 hasConcept C184235292 @default.
• W2042992682 hasConcept C185592680 @default.
• W2042992682 hasConcept C2529059 @default.
• W2042992682 hasConcept C502942594 @default.
• W2042992682 hasConcept C55493867 @default.
• W2042992682 hasConcept C62478195 @default.
• W2042992682 hasConcept C86803240 @default.
• W2042992682 hasConcept C93880895 @default.
• W2042992682 hasConcept C95444343 @default.
• W2042992682 hasConceptScore W2042992682C104317684 @default.
• W2042992682 hasConceptScore W2042992682C123233396 @default.
• W2042992682 hasConceptScore W2042992682C137620995 @default.
• W2042992682 hasConceptScore W2042992682C145059251 @default.
• W2042992682 hasConceptScore W2042992682C170493617 @default.
• W2042992682 hasConceptScore W2042992682C184235292 @default.
• W2042992682 hasConceptScore W2042992682C185592680 @default.
• W2042992682 hasConceptScore W2042992682C2529059 @default.
• W2042992682 hasConceptScore W2042992682C502942594 @default.
• W2042992682 hasConceptScore W2042992682C55493867 @default.
• W2042992682 hasConceptScore W2042992682C62478195 @default.
• W2042992682 hasConceptScore W2042992682C86803240 @default.
• W2042992682 hasConceptScore W2042992682C93880895 @default.
• W2042992682 hasConceptScore W2042992682C95444343 @default.
• W2042992682 hasIssue "11_Supplement" @default.
• W2042992682 hasLocation W20429926821 @default.
• W2042992682 hasOpenAccess W2042992682 @default.
• W2042992682 hasPrimaryLocation W20429926821 @default.
• W2042992682 hasRelatedWork W2000476522 @default.
• W2042992682 hasRelatedWork W2364007754 @default.
• W2042992682 hasRelatedWork W2365516742 @default.
• W2042992682 hasRelatedWork W2382776397 @default.
• W2042992682 hasRelatedWork W2900900388 @default.
• W2042992682 hasRelatedWork W2941352951 @default.
• W2042992682 hasRelatedWork W2982254530 @default.
• W2042992682 hasRelatedWork W3028626900 @default.
• W2042992682 hasRelatedWork W3208766048 @default.
• W2042992682 hasRelatedWork W4283740533 @default.
• W2042992682 hasVolume "12" @default.
• W2042992682 isParatext "false" @default.
• W2042992682 isRetracted "false" @default.
• W2042992682 magId "2042992682" @default.
• W2042992682 workType "article" @default.