Identification of a novel SHP-2 protein tyrosine phosphatase inhibitor

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dc.contributor.authorA Ju-
dc.contributor.authorH Seo-
dc.contributor.authorH Kim-
dc.contributor.authorByoung Chul Park-
dc.contributor.authorSung Goo Park-
dc.contributor.authorJeong Hoon Kim-
dc.contributor.authorH K Choi-
dc.contributor.authorK H Min-
dc.contributor.authorS Cho-
dc.date.accessioned2017-04-19T09:52:21Z-
dc.date.available2017-04-19T09:52:21Z-
dc.date.issued2014-
dc.identifier.issn00092673-
dc.identifier.uri10.1246/bcsj.20130221ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/11916-
dc.description.abstractThe Src homology 2 (SH2) domain-containing phosphatase 2 (SHP-2) is a nonreceptor protein tyrosine phosphatase (PTP) involved in extracellular- regulated kinase (ERK) activation. Recent studies have shown that gain-of-function mutations in SHP-2 are associated with several diseases, including LEOPARD syndrome, Noonan syndrome, and juvenile myelomonocytic leukemia. In this study, we identified the novel SHP-2 inhibitor 3-(1-benzimidazolylmethyl)-6-p-tolyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (MLS-001). SHP-2 activity was inhibited by MLS-001, whereas other types of PTPs, namely ACP1, CDC25A, DUSP3, DUSP14, DUSP18, DUSP22, DUSP23, DUSP26, and SSH3, were not. Furthermore, TCPTP and SHP-1 that are closely related to SHP-2 were not inhibited by the inhibitor. Kinetic studies with MLS-001 and SHP-2 revealed a competitive inhibition. The SHP-2 expressing cells treated with MLS-001 demonstrated reduced SHP-2 phosphatase activity, thereby suggesting that MLS-001 effectively passes through cell membranes. In addition, MLS-001 reduced SHP-2-mediated phosphorylation in the activation loop of ERK in cells. Therefore, MLS-001 could be a lead compound for developing a potent SHP-2 inhibitor.-
dc.publisherChemical Soc Japan-
dc.titleIdentification of a novel SHP-2 protein tyrosine phosphatase inhibitor-
dc.title.alternativeIdentification of a novel SHP-2 protein tyrosine phosphatase inhibitor-
dc.typeArticle-
dc.citation.titleBulletin of Chemical Society of Japan-
dc.citation.number3-
dc.citation.endPage424-
dc.citation.startPage420-
dc.citation.volume87-
dc.contributor.affiliatedAuthorByoung Chul Park-
dc.contributor.affiliatedAuthorSung Goo Park-
dc.contributor.affiliatedAuthorJeong Hoon Kim-
dc.contributor.alternativeName주안나-
dc.contributor.alternativeName서희연-
dc.contributor.alternativeName김희문-
dc.contributor.alternativeName박병철-
dc.contributor.alternativeName박성구-
dc.contributor.alternativeName김정훈-
dc.contributor.alternativeName최형균-
dc.contributor.alternativeName민경훈-
dc.contributor.alternativeName조사연-
dc.identifier.bibliographicCitationBulletin of Chemical Society of Japan, vol. 87, no. 3, pp. 420-424-
dc.identifier.doi10.1246/bcsj.20130221-
dc.description.journalClassY-
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Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
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