Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 하정미 | - |
dc.date.accessioned | 2024-04-04T02:43:38Z | - |
dc.date.available | 2024-04-04T02:43:38Z | - |
dc.date.issued | 2022-10-02 | - |
dc.identifier.citation | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | en_US |
dc.identifier.issn | 0223-5234 | en_US |
dc.identifier.uri | https://www.sciencedirect.com/science/article/pii/S0223523422007966 | en_US |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/189608 | - |
dc.description.abstract | Despite innumerable efforts to develop effective therapeutics, it is difficult to achieve breakthrough treatments for Alzheimer's disease (AD), and the main reason is probably the absence of a clear target. Here, we reveal c-Jun N-terminal kinase 3 (JNK3), a protein kinase explicitly expressed in the brain and involved in neuronal apoptosis, with a view toward providing effective treatment for AD. For many years, we have worked on JNK3 inhibitors and have discovered 2-aryl-1-pyrimidinyl-1H-imidazole-5-yl acetonitrile-based JNK3 inhibitors with superb potency (IC50 ˂ 1.0 nM) and excellent selectivity over other protein kinases including isoforms JNK1 (˃300 fold) and JNK2 (similar to 10 fold). Based on in vitro biological activity and DMPK properties, the lead compounds were selected for further in vivo studies. We confirmed that repeat administration of JNK3 inhibitors improved cognitive memory in APP/PS1 and the 3xTg mouse model. Overall, our results show that JNK3 could be a potential target protein for AD. | en_US |
dc.description.sponsorship | This work was financially supported by a National Research Foundation of Korea grant NRF-2019M3A9A8066500 (J.-M.H.) NRF2020R1A6A1A03042854 (Center for Proteinopathy), NRF2021R1A2C2007159 (J.-M.H.) and supported by an Institute of Information and Communications Technology Planning and Evaluation (IITP) grant funded by the Korean government (MSIT) (No.2020-0- 01343). | en_US |
dc.language | en_US | en_US |
dc.publisher | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER | en_US |
dc.relation.ispartofseries | v. 245, NO 1;1-20 | - |
dc.subject | JNK3 | en_US |
dc.subject | Imidazole | en_US |
dc.subject | Neurodegenerative diseases | en_US |
dc.subject | Alzheimer’s disease | en_US |
dc.subject | APP/PS1 | en_US |
dc.subject | 3xTg | en_US |
dc.subject | mouse | en_US |
dc.title | Discovery of novel imidazole chemotypes as isoform-selective JNK3 inhibitors for the treatment of Alzheimer's disease | en_US |
dc.type | Article | en_US |
dc.relation.no | 1 | - |
dc.relation.volume | 245 | - |
dc.identifier.doi | https://doi.org/10.1016/j.ejmech.2022.114894 | en_US |
dc.relation.page | 114894-114913 | - |
dc.relation.journal | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.contributor.googleauthor | Jun, Joonhong | - |
dc.contributor.googleauthor | Yang, Songyi | - |
dc.contributor.googleauthor | Lee, Junghun | - |
dc.contributor.googleauthor | Moon, Hyungwoo | - |
dc.contributor.googleauthor | Kim, Jinwoong | - |
dc.contributor.googleauthor | Jung, Hoyong | - |
dc.contributor.googleauthor | Im, Daseul | - |
dc.contributor.googleauthor | Oh, Youri | - |
dc.contributor.googleauthor | Jang, Miyoung | - |
dc.contributor.googleauthor | Hah, Jung-Mi | - |
dc.relation.code | 2023041495 | - |
dc.sector.campus | E | - |
dc.sector.daehak | COLLEGE OF PHARMACY[E] | - |
dc.sector.department | DEPARTMENT OF PHARMACY | - |
dc.identifier.pid | jhah | - |
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