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dc.contributor.authorLim, Ji Woong-
dc.contributor.authorKim, Seok Kyu-
dc.contributor.authorChoi, Seo Yun-
dc.contributor.authorKim, Dong Hoi-
dc.contributor.authorGadhe, Changdev G.-
dc.contributor.authorLee, Hae Nim-
dc.contributor.authorKim, Hyo-Ji-
dc.contributor.authorKim, Jina-
dc.contributor.authorCho, Sung Jin-
dc.contributor.authorHwang, Hayoung-
dc.contributor.authorSeong, Jihye-
dc.contributor.authorJeong, Kyu-Sung-
dc.contributor.authorLee, Jae Yeol-
dc.contributor.authorLim, Sang Min-
dc.contributor.authorLee, Jae Wook-
dc.contributor.authorPae, Ae Nim-
dc.date.accessioned2024-01-19T22:00:39Z-
dc.date.available2024-01-19T22:00:39Z-
dc.date.created2021-09-03-
dc.date.issued2018-09-05-
dc.identifier.issn0223-5234-
dc.identifier.urihttps://pubs.kist.re.kr/handle/201004/120923-
dc.description.abstractSH2 domain-containing inositol 5'-phosphatase 2 (SHIP2) is a lipid phosphatase that produce phosphatidylinositol 3,4-bisphosphate (PI(3,4)P-2) from phosphatidylinositol 3,4,5-triphosphate (PI(3,4,5)P-3), and is involved in many diseases such as neurodegenerative diseases. A recent report demonstrating that SHIP2 inhibition decreased tau hyperphosphorylation induced by amyloid beta and rescued memory impairment in a transgenic Alzheimer's disease mouse model indicates SHIP2 can be a promising therapeutic target for Alzheimer's disease. In the present study, we have developed novel, potent SHIP2 inhibitors by extensive structural elaboration of crizotinib discovered from a high-throughput screening. Our representative compound 43 potently inhibited SHIP2 activity as well as GSK3 beta activation in HT22 neuronal cells. It was also shown that 43 has favorable physicochemical properties, especially high brain penetration. Considering SHIP2 is one of key signal mediators for tau hyperphosphorylation, our potent SHIP2 inhibitor 43 may function as a promising lead compound for the treatment of Alzheimer's disease. (C) 2018 Elsevier Masson SAS. All rights reserved.-
dc.languageEnglish-
dc.publisherELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER-
dc.subjectAMYLOID-BETA-
dc.subjectDISCOVERY-
dc.subjectPROTEIN-
dc.subjectPHOSPHATASE-
dc.subjectMOLECULE-
dc.subjectTAU-
dc.subjectPHOSPHORYLATION-
dc.subjectACTIVATION-
dc.subjectPATHOLOGY-
dc.subjectINSIGHTS-
dc.titleIdentification of crizotinib derivatives as potent SHIP2 inhibitors for the treatment of Alzheimer's disease-
dc.typeArticle-
dc.identifier.doi10.1016/j.ejmech.2018.07.071-
dc.description.journalClass1-
dc.identifier.bibliographicCitationEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.157, pp.405 - 422-
dc.citation.titleEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY-
dc.citation.volume157-
dc.citation.startPage405-
dc.citation.endPage422-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.identifier.wosid000447480000030-
dc.identifier.scopusid2-s2.0-85051274310-
dc.relation.journalWebOfScienceCategoryChemistry, Medicinal-
dc.relation.journalResearchAreaPharmacology & Pharmacy-
dc.type.docTypeArticle-
dc.subject.keywordPlusAMYLOID-BETA-
dc.subject.keywordPlusDISCOVERY-
dc.subject.keywordPlusPROTEIN-
dc.subject.keywordPlusPHOSPHATASE-
dc.subject.keywordPlusMOLECULE-
dc.subject.keywordPlusTAU-
dc.subject.keywordPlusPHOSPHORYLATION-
dc.subject.keywordPlusACTIVATION-
dc.subject.keywordPlusPATHOLOGY-
dc.subject.keywordPlusINSIGHTS-
dc.subject.keywordAuthorSH2 domain-containing inositol 5-phosphatase 2-
dc.subject.keywordAuthorAlzheimer&apos-
dc.subject.keywordAuthors disease-
dc.subject.keywordAuthorCrizotinib-
dc.subject.keywordAuthorTau-
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