Cited 10 times in

7-cyclopenty1-5-(4-phenoxypheny1)-7H-pyrrolo[2,3-d] pyrimidin-4-ylamine inhibits the proliferation and migration of vascular smooth muscle cells by suppressing ERK and Akt pathways

DC Field Value Language
dc.date.accessioned2023-08-22T07:16:18Z-
dc.date.available2023-08-22T07:16:18Z-
dc.date.issued2017-03-
dc.identifier.issn0014-2999-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/196078-
dc.description.abstractExcessive vascular smooth muscle cell (VSMC) proliferation and migration after vascular injury significantly contributes to the development of occlusive vascular disease. Therefore, inhibiting the proliferation and migration of VSMCs is a validated therapeutic modality for occlusive vascular disease such as atherosclerosis and restenosis. In the present study, we screened chemical compounds for their anti-proliferative effects on VSMCs using multiple approaches, such as MTT assays, wound healing assays, and trans-well migration assays. Our data indicate that 7-cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d] pyrimidin-4-ylamine, a lymphocyte-specific protein tyrosine kinase (Lck) inhibitor, significantly inhibited both VSMC proliferation and migration. 7-cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine suppresses VSMC proliferation and migration via down-regulating the protein kinase B (Akt) and extracellular signal regulated kinase (ERK) pathways, and it significantly decreased the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 and, the phosphorylation of retinoblastoma protein (pRb). Additionally, 7-cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d] pyrimidin-4-ylamine suppressed the migration of VSMCs from endothelium-removed aortic rings, as well as neointima formation following rat carotid balloon injury. The present study identified 7-cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine as a potent VSMC proliferation and migration inhibitor and warrants further studies to elucidate its more detailed molecular mechanisms, such as its primary target, and to further validate its in vivo efficacy as a therapeutic agent for pathologic vascular conditions, such as restenosis and atherosclerosis.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherElsevier Science-
dc.relation.isPartOfEUROPEAN JOURNAL OF PHARMACOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAnimals-
dc.subject.MESHCell Cycle / drug effects-
dc.subject.MESHCell Movement / drug effects*-
dc.subject.MESHCell Proliferation / drug effects-
dc.subject.MESHCell Survival / drug effects-
dc.subject.MESHDose-Response Relationship, Drug-
dc.subject.MESHDrug Evaluation, Preclinical-
dc.subject.MESHExtracellular Signal-Regulated MAP Kinases / metabolism*-
dc.subject.MESHMuscle, Smooth, Vascular / cytology*-
dc.subject.MESHProto-Oncogene Proteins c-akt / metabolism*-
dc.subject.MESHPyrimidines / pharmacology*-
dc.subject.MESHPyrroles / pharmacology*-
dc.subject.MESHRats-
dc.subject.MESHRats, Sprague-Dawley-
dc.subject.MESHSignal Transduction / drug effects*-
dc.title7-cyclopenty1-5-(4-phenoxypheny1)-7H-pyrrolo[2,3-d] pyrimidin-4-ylamine inhibits the proliferation and migration of vascular smooth muscle cells by suppressing ERK and Akt pathways-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentOther-
dc.identifier.doi10.1016/j.ejphar.2017.02.004-
dc.relation.journalcodeJ00842-
dc.identifier.eissn1879-0712-
dc.identifier.pmid28185804-
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0014299917300675-
dc.subject.keyword3-d] pyrimidin-4-ylamine-
dc.subject.keyword7-cyclopentyl-5-(4-phenoxyphenyl)−7H-pyrrolo[2-
dc.subject.keywordMigration-
dc.subject.keywordProliferation-
dc.subject.keywordVSMC-
dc.citation.volume798-
dc.citation.startPage35-
dc.citation.endPage42-
dc.identifier.bibliographicCitationEUROPEAN JOURNAL OF PHARMACOLOGY, Vol.798 : 35-42, 2017-03-
Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.