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dc.contributor.authorNam, Yunju-
dc.contributor.authorKim, Chan-
dc.contributor.authorHan, Junghee-
dc.contributor.authorRyu Seong-Shick-
dc.contributor.authorCho, Hanna-
dc.contributor.authorSong, Chiman-
dc.contributor.authorKim, Nam Doo-
dc.contributor.authorKim, Namkyoung-
dc.contributor.authorSim, Taebo-
dc.date.accessioned2024-01-12T02:33:36Z-
dc.date.available2024-01-12T02:33:36Z-
dc.date.created2023-01-04-
dc.date.issued2023-01-
dc.identifier.issn2072-6694-
dc.identifier.urihttps://pubs.kist.re.kr/handle/201004/75861-
dc.description.abstractc-KIT is a promising therapeutic target against gastrointestinal stromal tumor (GIST). In order to identify novel c-KIT inhibitors capable of overcoming imatinib resistance, we synthesized 31 novel thiazolo[5,4-b]pyridine derivatives and performed SAR studies. We observed that, among these substances, 6r is capable of inhibiting significantly c-KIT and suppressing substantially proliferation of GIST-T1 cancer cells. It is of note that 6r is potent against a c-KIT V560G/D816V double mutant resistant to imatinib. Compared with sunitinib, 6r possesses higher differential cytotoxicity on c-KIT D816V Ba/F3 cells relative to parental Ba/F3 cells. In addition, kinase panel profiling reveals that 6r has reasonable kinase selectivity. It was found that 6r remarkably attenuates proliferation of cancer cells via blockade of c-KIT downstream signaling, and induction of apoptosis and cell cycle arrest. Furthermore, 6r notably suppresses migration and invasion, as well as anchorage-independent growth of GIST-T1 cells. This study provides useful SAR information for the design of novel c-KIT inhibitors overcoming imatinib-resistance.-
dc.languageEnglish-
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI)-
dc.titleIdentification of Thiazolo[5,4-b]pyridine Derivatives as c-KIT Inhibitors for Overcoming Imatinib Resistance-
dc.typeArticle-
dc.identifier.doi10.3390/cancers15010143-
dc.description.journalClass1-
dc.identifier.bibliographicCitationCancers, v.15, no.1-
dc.citation.titleCancers-
dc.citation.volume15-
dc.citation.number1-
dc.description.isOpenAccessY-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.identifier.wosid000910414700001-
dc.relation.journalWebOfScienceCategoryOncology-
dc.relation.journalResearchAreaOncology-
dc.type.docTypeArticle-
dc.subject.keywordPlusGASTROINTESTINAL STROMAL TUMORS-
dc.subject.keywordPlusTYROSINE KINASE-
dc.subject.keywordPlusCELL-LINE-
dc.subject.keywordPlusGATEKEEPER MUTANT-
dc.subject.keywordPlusMUTATIONS-
dc.subject.keywordPlusRECEPTOR-
dc.subject.keywordPlusDISCOVERY-
dc.subject.keywordPlusACTIVATION-
dc.subject.keywordPlusMECHANISMS-
dc.subject.keywordPlusSUNITINIB-
dc.subject.keywordAuthorc-KIT-
dc.subject.keywordAuthorGIST-
dc.subject.keywordAuthorGIST-T1-
dc.subject.keywordAuthorHMC1-
dc.subject.keywordAuthor2-
dc.subject.keywordAuthorimatinib resistance-
dc.subject.keywordAuthorthiazolo[5-
dc.subject.keywordAuthor4-b]pyridine-
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