Cited 3 times in
Synthetic Strategies for Improving Solubility: Optimization of Novel Pyrazolo[1,5- a]pyrimidine CFTR Activator That Ameliorates Dry Eye Disease
DC Field | Value | Language |
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dc.contributor.author | 김태임 | - |
dc.contributor.author | 서경률 | - |
dc.contributor.author | 전익현 | - |
dc.date.accessioned | 2023-03-22T02:07:04Z | - |
dc.date.available | 2023-03-22T02:07:04Z | - |
dc.date.issued | 2023-01 | - |
dc.identifier.issn | 0022-2623 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/193524 | - |
dc.description.abstract | Dry eye disease (DED) is one of the most prevalent ocular diseases but has limited treatment options. Cystic fibrosis transmembrane conductance regulator (CFTR), a major chloride channel that stimulates fluid secretion in the ocular surface, may pave the way for new therapeutic strategies for DED. Herein, we report the optimization of Cact-3, a potent CFTR activator with poor solubility, to 16d, a potent CFTR activator with suitable solubility for eye drop formulation. Notably, 16d was well distributed in target tissues including cornea and conjunctiva with minimal systemic exposure in rabbit. Topical ocular instillation of 16d significantly enhanced tear secretion and improved corneal erosion in a mouse model of DED. In addition, 16d significantly reduced mRNA expression of pro-inflammatory cytokines including IL-1β, IL-17, and TNF-α and MMP2 in cornea and conjunctiva of DED mice. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | American Chemical Society | - |
dc.relation.isPartOf | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Conjunctiva / metabolism | - |
dc.subject.MESH | Cornea | - |
dc.subject.MESH | Cystic Fibrosis Transmembrane Conductance Regulator* / genetics | - |
dc.subject.MESH | Cystic Fibrosis Transmembrane Conductance Regulator* / metabolism | - |
dc.subject.MESH | Dry Eye Syndromes* / drug therapy | - |
dc.subject.MESH | Dry Eye Syndromes* / genetics | - |
dc.subject.MESH | Dry Eye Syndromes* / metabolism | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Pyrimidines / metabolism | - |
dc.subject.MESH | Pyrimidines / pharmacology | - |
dc.subject.MESH | Pyrimidines / therapeutic use | - |
dc.subject.MESH | Rabbits | - |
dc.subject.MESH | Solubility | - |
dc.subject.MESH | Tears / metabolism | - |
dc.title | Synthetic Strategies for Improving Solubility: Optimization of Novel Pyrazolo[1,5- a]pyrimidine CFTR Activator That Ameliorates Dry Eye Disease | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Ophthalmology (안과학교실) | - |
dc.contributor.googleauthor | Bo Yi Kim | - |
dc.contributor.googleauthor | Changmok Oh | - |
dc.contributor.googleauthor | Dongkyu Jeon | - |
dc.contributor.googleauthor | Ikhyun Jun | - |
dc.contributor.googleauthor | Ho K Lee | - |
dc.contributor.googleauthor | Bo-Rahm Kim | - |
dc.contributor.googleauthor | Jinhong Park | - |
dc.contributor.googleauthor | Kyoung Yul Seo | - |
dc.contributor.googleauthor | Kyeong-A Kim | - |
dc.contributor.googleauthor | Dami Lim | - |
dc.contributor.googleauthor | Seolhee Lee | - |
dc.contributor.googleauthor | Jooyun Lee | - |
dc.contributor.googleauthor | Hongchul Yoon | - |
dc.contributor.googleauthor | Tae-Im Kim | - |
dc.contributor.googleauthor | Wan Namkung | - |
dc.identifier.doi | 10.1021/acs.jmedchem.2c01382 | - |
dc.contributor.localId | A01080 | - |
dc.contributor.localId | A01870 | - |
dc.contributor.localId | A03541 | - |
dc.relation.journalcode | J01588 | - |
dc.identifier.eissn | 1520-4804 | - |
dc.identifier.pmid | 36573286 | - |
dc.contributor.alternativeName | Kim, Tae Im | - |
dc.contributor.affiliatedAuthor | 김태임 | - |
dc.contributor.affiliatedAuthor | 서경률 | - |
dc.contributor.affiliatedAuthor | 전익현 | - |
dc.citation.volume | 66 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 413 | - |
dc.citation.endPage | 434 | - |
dc.identifier.bibliographicCitation | JOURNAL OF MEDICINAL CHEMISTRY, Vol.66(1) : 413-434, 2023-01 | - |
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