Identification of 4-Phenoxyquinoline Based Inhibitors for L1196M Mutant of Anaplastic Lymphoma Kinase by Structure-Based Design
DC Field | Value | Language |
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dc.contributor.author | Shinmee Mah | - |
dc.contributor.author | Jung Hee Park | - |
dc.contributor.author | Hoi-Yun Jung | - |
dc.contributor.author | Kukcheol Ahn | - |
dc.contributor.author | Soyeon Choi | - |
dc.contributor.author | Hyun Seop Tae | - |
dc.contributor.author | Kyung Hee Jung | - |
dc.contributor.author | Jin Kyung Rho | - |
dc.contributor.author | Jae Cheol Lee | - |
dc.contributor.author | Soon-Sun Hong | - |
dc.contributor.author | Sungwoo Hong | - |
dc.date.available | 2018-07-18T02:08:19Z | - |
dc.date.created | 2018-03-15 | - |
dc.date.issued | 2017-11 | - |
dc.identifier.issn | 0022-2623 | - |
dc.identifier.uri | https://pr.ibs.re.kr/handle/8788114/4775 | - |
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 © 2017 American Chemical Society | - |
dc.language | 영어 | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.title | Identification of 4-Phenoxyquinoline Based Inhibitors for L1196M Mutant of Anaplastic Lymphoma Kinase by Structure-Based Design | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.identifier.wosid | 000416500200006 | - |
dc.identifier.scopusid | 2-s2.0-85034995129 | - |
dc.identifier.rimsid | 62395 | ko |
dc.contributor.affiliatedAuthor | Shinmee Mah | - |
dc.contributor.affiliatedAuthor | Hoi-Yun Jung | - |
dc.contributor.affiliatedAuthor | Kukcheol Ahn | - |
dc.contributor.affiliatedAuthor | Soyeon Choi | - |
dc.contributor.affiliatedAuthor | Hyun Seop Tae | - |
dc.contributor.affiliatedAuthor | Sungwoo Hong | - |
dc.identifier.doi | 10.1021/acs.jmedchem.7b01039 | - |
dc.identifier.bibliographicCitation | JOURNAL OF MEDICINAL CHEMISTRY, v.60, no.22, pp.9205 - 9221 | - |
dc.relation.isPartOf | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.citation.title | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.citation.volume | 60 | - |
dc.citation.number | 22 | - |
dc.citation.startPage | 9205 | - |
dc.citation.endPage | 9221 | - |
dc.embargo.liftdate | 9999-12-31 | - |
dc.embargo.terms | 9999-12-31 | - |
dc.description.journalClass | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
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 | - |