Discovery of a Novel Triazolopyridine Derivative as a Tankyrase Inhibitor
DC Field | Value | Language |
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dc.contributor.author | Ryu, Hwani | - |
dc.contributor.author | Nam, Ky-Youb | - |
dc.contributor.author | Kim, Hyo Jeong | - |
dc.contributor.author | Song, Jie-Young | - |
dc.contributor.author | Hwang, Sang-Gu | - |
dc.contributor.author | Kim, Jae Sung | - |
dc.contributor.author | Kim, Joon | - |
dc.contributor.author | Ahn, Jiyeon | - |
dc.date.accessioned | 2022-02-28T04:42:25Z | - |
dc.date.available | 2022-02-28T04:42:25Z | - |
dc.date.created | 2022-02-09 | - |
dc.date.issued | 2021-07 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/137215 | - |
dc.description.abstract | More than 80% of colorectal cancer patients have adenomatous polyposis coli (APC) mutations, which induce abnormal WNT/beta-catenin activation. Tankyrase (TNKS) mediates the release of active beta-catenin, which occurs regardless of the ligand that translocates into the nucleus by AXIN degradation via the ubiquitin-proteasome pathway. Therefore, TNKS inhibition has emerged as an attractive strategy for cancer therapy. In this study, we identified pyridine derivatives by evaluating in vitro TNKS enzyme activity and investigated N-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-1-(2-cyanophenyl)piperidine-4-carboxamide (TI-12403) as a novel TNKS inhibitor. TI-12403 stabilized AXIN2, reduced active beta-catenin, and downregulated beta-catenin target genes in COLO320DM and DLD-1 cells. The antitumor activities of TI-12403 were confirmed by the viability of the colorectal cancer cells and its lack of visible toxicity in DLD-1 xenograft mouse model. In addition, combined 5-FU and TI-12403 treatment synergistically inhibited proliferation to a greater extent than that in a single drug treatment. Our observations suggest that TI-12403, a novel selective TNKS1 inhibitor, may be a suitable compound for anticancer drug development. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | MDPI | - |
dc.subject | POLY(ADP-RIBOSE) POLYMERASE | - |
dc.subject | STRUCTURAL BASIS | - |
dc.subject | WNT | - |
dc.subject | IDENTIFICATION | - |
dc.subject | DEGRADATION | - |
dc.subject | RESISTANCE | - |
dc.subject | CANCER | - |
dc.subject | AXIN | - |
dc.subject | PARP | - |
dc.title | Discovery of a Novel Triazolopyridine Derivative as a Tankyrase Inhibitor | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Joon | - |
dc.identifier.doi | 10.3390/ijms22147330 | - |
dc.identifier.scopusid | 2-s2.0-85112484790 | - |
dc.identifier.wosid | 000676469600001 | - |
dc.identifier.bibliographicCitation | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.22, no.14 | - |
dc.relation.isPartOf | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | - |
dc.citation.title | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | - |
dc.citation.volume | 22 | - |
dc.citation.number | 14 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.subject.keywordPlus | AXIN | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | DEGRADATION | - |
dc.subject.keywordPlus | IDENTIFICATION | - |
dc.subject.keywordPlus | PARP | - |
dc.subject.keywordPlus | POLY(ADP-RIBOSE) POLYMERASE | - |
dc.subject.keywordPlus | RESISTANCE | - |
dc.subject.keywordPlus | STRUCTURAL BASIS | - |
dc.subject.keywordPlus | WNT | - |
dc.subject.keywordAuthor | WNT/beta-catenin pathway | - |
dc.subject.keywordAuthor | colorectal cancer | - |
dc.subject.keywordAuthor | combination therapy | - |
dc.subject.keywordAuthor | tankyrase | - |
dc.subject.keywordAuthor | tankyrase inhibitor | - |
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