DC Field | Value | Language |
---|---|---|
dc.contributor.author | Mah, Shinmee | ko |
dc.contributor.author | Park, Jung Hee | ko |
dc.contributor.author | Jung, Hoi Yun | ko |
dc.contributor.author | Ahn, Kukcheol | ko |
dc.contributor.author | Choi, Soyeon | ko |
dc.contributor.author | Tae, Hyun Seo | ko |
dc.contributor.author | Jung, Kyung Hee | ko |
dc.contributor.author | Rho, Jin Kyung | ko |
dc.contributor.author | Lee, Jae Cheol | ko |
dc.contributor.author | Hong, Soon-Sun | ko |
dc.contributor.author | Hong, Sungwoo | ko |
dc.date.accessioned | 2017-12-19T03:02:13Z | - |
dc.date.available | 2017-12-19T03:02:13Z | - |
dc.date.created | 2017-12-11 | - |
dc.date.created | 2017-12-11 | - |
dc.date.issued | 2017-11 | - |
dc.identifier.citation | JOURNAL OF MEDICINAL CHEMISTRY, v.60, no.22, pp.9205 - 9221 | - |
dc.identifier.issn | 0022-2623 | - |
dc.identifier.uri | http://hdl.handle.net/10203/228596 | - |
dc.description.abstract | Dysregulation of anaplastic lymphoma kinase (ALK) has been detected in nonsmall cell lung cancer (NSCLC) in the form of EML4-ALK fusion. Secondary mutations opposing activity of the first generation ALK inhibitor crizotinib came into existence, requiring mutation-targeting drug discovery for the powerful second-line treatment. In this study, we report 4-phenoxyquinoline-based inhibitors that overcome crizotinib resistance to ALK L1196M, discovered by the fragment-growing strategy. The protonation of 4-aminoquinoline core could interrupt the ability the N atom of quinoline to act as a hydrogen bond acceptor; therefore, the pK(a) and calculated ionization pH values of relevant pyridine-based core moieties were carefully analyzed. The replacement of amine linkage with ether resulted in single-digit nanomolar range inhibitors. The inhibitors exhibited significant antiproliferative effects on H2228 CR crizotinib-resistant cells by decreasing PI3K/AKT and MAPK signaling. This work constitutes the first of ionization pH on activity in this system. | - |
dc.language | English | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.subject | CELL LUNG-CANCER | - |
dc.subject | RECEPTOR TYROSINE KINASE | - |
dc.subject | EML4-ALK FUSION GENE | - |
dc.subject | CRIZOTINIB RESISTANCE | - |
dc.subject | ALK INHIBITORS | - |
dc.subject | DISCOVERY | - |
dc.subject | MUTATION | - |
dc.subject | CERITINIB | - |
dc.subject | ALECTINIB | - |
dc.subject | OVERCOME | - |
dc.title | Identification of 4-Phenoxyquinoline Based Inhibitors for L1196M Mutant of Anaplastic Lymphoma Kinase by Structure-Based Design | - |
dc.type | Article | - |
dc.identifier.wosid | 000416500200006 | - |
dc.identifier.scopusid | 2-s2.0-85034995129 | - |
dc.type.rims | ART | - |
dc.citation.volume | 60 | - |
dc.citation.issue | 22 | - |
dc.citation.beginningpage | 9205 | - |
dc.citation.endingpage | 9221 | - |
dc.citation.publicationname | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.identifier.doi | 10.1021/acs.jmedchem.7b01039 | - |
dc.contributor.localauthor | Hong, Sungwoo | - |
dc.contributor.nonIdAuthor | Park, Jung Hee | - |
dc.contributor.nonIdAuthor | Ahn, Kukcheol | - |
dc.contributor.nonIdAuthor | Choi, Soyeon | - |
dc.contributor.nonIdAuthor | Tae, Hyun Seo | - |
dc.contributor.nonIdAuthor | Jung, Kyung Hee | - |
dc.contributor.nonIdAuthor | Rho, Jin Kyung | - |
dc.contributor.nonIdAuthor | Lee, Jae Cheol | - |
dc.contributor.nonIdAuthor | Hong, Soon-Sun | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | CELL LUNG-CANCER | - |
dc.subject.keywordPlus | RECEPTOR TYROSINE KINASE | - |
dc.subject.keywordPlus | EML4-ALK FUSION GENE | - |
dc.subject.keywordPlus | CRIZOTINIB RESISTANCE | - |
dc.subject.keywordPlus | ALK INHIBITORS | - |
dc.subject.keywordPlus | DISCOVERY | - |
dc.subject.keywordPlus | MUTATION | - |
dc.subject.keywordPlus | CERITINIB | - |
dc.subject.keywordPlus | ALECTINIB | - |
dc.subject.keywordPlus | OVERCOME | - |
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