Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 이윤실 | * |
dc.contributor.author | 강수성 | * |
dc.contributor.author | 서원효 | * |
dc.contributor.author | 진희 | * |
dc.date.accessioned | 2024-02-06T16:31:08Z | - |
dc.date.available | 2024-02-06T16:31:08Z | - |
dc.date.issued | 2023 | * |
dc.identifier.issn | 0022-2623 | * |
dc.identifier.other | OAK-34571 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/267009 | - |
dc.description.abstract | Janus kinase 1 (JAK1) plays a pivotal role in regulating inflammation and fibrosis via the JAK/STAT signaling pathway, making it a promising target for associated diseases. In this study, we explored the modification of an N-methyl 1H-pyrrolo[2,3-b]pyridine-5-carboxylate core, leading to the identification of 4-(((2S,4S)-1-(4-trifluoromethyl)-2-methylpiperidin-4-yl)amino)-N-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxamide (36b) as a highly potent and selective JAK1 inhibitor. Compound 36b exhibited an impressive IC50 value of 0.044 nM for JAK1 and demonstrated remarkable selectivity of 382-fold, 210-fold, and 1325-fold specificity over JAK2, JAK3, and TYK2, respectively. The kinase panel assays further confirmed its specificity, and cell-based experiments established its efficacy in inhibiting JAK1-STAT phosphorylation in human L-132 or SK-MES-1 cells. Pharmacokinetic studies revealed that compound 36b boasts an oral bioavailability exceeding 36%. In a bleomycin-induced fibrosis mouse model, compound 36b significantly reduced STAT3 phosphorylation, resulting in improvement in body weight and reduced collagen deposition, all achieved without significant side effects. © 2023 American Chemical Society. | * |
dc.language | English | * |
dc.publisher | American Chemical Society | * |
dc.title | Identification and Biological Evaluation of a Potent and Selective JAK1 Inhibitor for the Treatment of Pulmonary Fibrosis | * |
dc.type | Article | * |
dc.relation.issue | 23 | * |
dc.relation.volume | 66 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 16342 | * |
dc.relation.lastpage | 16363 | * |
dc.relation.journaltitle | Journal of Medicinal Chemistry | * |
dc.identifier.doi | 10.1021/acs.jmedchem.3c01712 | * |
dc.identifier.wosid | WOS:001141565500001 | * |
dc.identifier.scopusid | 2-s2.0-85179604163 | * |
dc.author.google | Park | * |
dc.author.google | Eunsun | * |
dc.author.google | Seolhee | * |
dc.author.google | Lee | * |
dc.author.google | Sun Joo | * |
dc.author.google | Jeong | * |
dc.author.google | Dayeon | * |
dc.author.google | Jin | * |
dc.author.google | Hee | * |
dc.author.google | Moon | * |
dc.author.google | Heegyum | * |
dc.author.google | Cha | * |
dc.author.google | Boksik | * |
dc.author.google | Kim | * |
dc.author.google | Dayea | * |
dc.author.google | Ma | * |
dc.author.google | Seonghee | * |
dc.author.google | Seo | * |
dc.author.google | Wonhyo | * |
dc.author.google | Han | * |
dc.author.google | Seung-Hee | * |
dc.author.google | Yun-Sil | * |
dc.author.google | Kang | * |
dc.author.google | Soosung | * |
dc.contributor.scopusid | 이윤실(17137192000) | * |
dc.contributor.scopusid | 강수성(56177300500) | * |
dc.contributor.scopusid | 서원효(56335935100) | * |
dc.contributor.scopusid | 진희(55447035000) | * |
dc.date.modifydate | 20240315114146 | * |