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Identification of Thiazolo[5,4- b]pyridine Derivatives as c-KIT Inhibitors for Overcoming Imatinib Resistance

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dc.contributor.author심태보-
dc.contributor.author조한나-
dc.date.accessioned2023-03-03T02:59:37Z-
dc.date.available2023-03-03T02:59:37Z-
dc.date.issued2023-01-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/192950-
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.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherMDPI-
dc.relation.isPartOfCANCERS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleIdentification of Thiazolo[5,4- b]pyridine Derivatives as c-KIT Inhibitors for Overcoming Imatinib Resistance-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentBioMedical Science Institute (의생명과학부)-
dc.contributor.googleauthorYunju Nam-
dc.contributor.googleauthorChan Kim-
dc.contributor.googleauthorJunghee Han-
dc.contributor.googleauthorSeongShick Ryu-
dc.contributor.googleauthorHanna Cho-
dc.contributor.googleauthorChiman Song-
dc.contributor.googleauthorNam Doo Kim-
dc.contributor.googleauthorNamkyoung Kim-
dc.contributor.googleauthorTaebo Sim-
dc.identifier.doi10.3390/cancers15010143-
dc.contributor.localIdA05926-
dc.relation.journalcodeJ03449-
dc.identifier.eissn2072-6694-
dc.identifier.pmid36612139-
dc.subject.keywordGIST-
dc.subject.keywordGIST-T1-
dc.subject.keywordHMC1.2-
dc.subject.keywordc-KIT-
dc.subject.keywordimatinib resistance-
dc.subject.keywordthiazolo[5,4-b]pyridine-
dc.contributor.alternativeNameSim, Taebo-
dc.contributor.affiliatedAuthor심태보-
dc.citation.volume15-
dc.citation.number1-
dc.citation.startPage143-
dc.identifier.bibliographicCitationCANCERS, Vol.15(1) : 143, 2023-01-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers

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