Novel Hypoxia-Inducible Factor 1 alpha (HIF-1 alpha) Inhibitors for Angiogenesis-Related Ocular Diseases: Discovery of a Novel Scaffold via Ring-Truncation Strategy
DC Field | Value | Language |
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dc.contributor.author | An, Hongchan | - |
dc.contributor.author | Lee, Seungbeom | - |
dc.contributor.author | Lee, Jung Mm | - |
dc.contributor.author | Jo, Dong Hyun | - |
dc.contributor.author | Kim, Joohwan | - |
dc.contributor.author | Jeong, Yoo-Seong | - |
dc.contributor.author | Heo, Mi Jeong | - |
dc.contributor.author | Cho, Chang Sik | - |
dc.contributor.author | Choi, Hoon | - |
dc.contributor.author | Seo, Ji Hae | - |
dc.contributor.author | Hwang, Seyeon | - |
dc.contributor.author | Lim, Jihye | - |
dc.contributor.author | Kim, Taewoo | - |
dc.contributor.author | Jun, Hyoung Oh | - |
dc.contributor.author | Sim, Jaehoon | - |
dc.contributor.author | Lim, Changjin | - |
dc.contributor.author | Hur, Joonseong | - |
dc.contributor.author | Ahn, Jungmin | - |
dc.contributor.author | Kim, Hyun Su | - |
dc.contributor.author | Seo, Seung-Yong | - |
dc.contributor.author | Na, Younghwa | - |
dc.contributor.author | Kim, Seok-Ho | - |
dc.contributor.author | Lee, Jeewoo | - |
dc.contributor.author | Lee, Jeeyeon | - |
dc.contributor.author | Chung, Suk-Jae | - |
dc.contributor.author | Kyu, Young-Myeong | - |
dc.contributor.author | Kim, Kyu-Won | - |
dc.contributor.author | Kim, Sang Geon | - |
dc.contributor.author | Kim, Jeong Hun | - |
dc.contributor.author | Suh, Young-Ger | - |
dc.date.available | 2020-02-27T08:43:01Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2018-10-25 | - |
dc.identifier.issn | 0022-2623 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/3201 | - |
dc.description.abstract | Ocular diseases featuring pathologic neovascularization are the leading cause of blindness, and anti-VEGF agents have been conventionally used to treat these diseases. Recently, regulating factors upstream of VEGF, such as HIF-1 alpha, have emerged as a desirable therapeutic approach because the use of anti-VEGF agents is currently being reconsidered due to the VEGF action as a trophic factor. Here, we report a novel scaffold discovered through the complete structure-activity relationship of ring-truncated deguelin analogs in HIF-1 alpha inhibition. Interestingly, analog 6i possessing a 2-fluorobenzene moiety instead of a dimethoxybenzene moiety exhibited excellent HIF-1 alpha inhibitory activity, with an IC50 value of 100 nM. In particular, the further ring-truncated analog 34f, which showed enhanced HIF-la inhibitory activity compared to analog 2 previously reported by us, inhibited in vitro angiogenesis and effectively suppressed hypoxia-mediated retinal neovascularization. Importantly, the heteroatom-substituted benzene ring as a key structural feature of analog 34f was identified as a novel scaffold for HIF-1 alpha inhibitors that can be used in lieu of a chromene ring. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.relation.isPartOf | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.subject | OXYGEN-INDUCED RETINOPATHY | - |
dc.subject | 90 HSP90 INHIBITORS | - |
dc.subject | FACTOR-I HIF-1 | - |
dc.subject | RETINAL NEOVASCULARIZATION | - |
dc.subject | COMBINATORIAL LIBRARIES | - |
dc.subject | BIOLOGICAL EVALUATION | - |
dc.subject | PRIVILEGED STRUCTURES | - |
dc.subject | DEGUELIN DERIVATIVES | - |
dc.subject | FACTOR PATHWAY | - |
dc.subject | VEGF | - |
dc.title | Novel Hypoxia-Inducible Factor 1 alpha (HIF-1 alpha) Inhibitors for Angiogenesis-Related Ocular Diseases: Discovery of a Novel Scaffold via Ring-Truncation Strategy | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000448754900019 | - |
dc.identifier.doi | 10.1021/acs.jmedchem.8b00971 | - |
dc.identifier.bibliographicCitation | JOURNAL OF MEDICINAL CHEMISTRY, v.61, no.20, pp.9266 - 9286 | - |
dc.identifier.scopusid | 2-s2.0-85055034698 | - |
dc.citation.endPage | 9286 | - |
dc.citation.startPage | 9266 | - |
dc.citation.title | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.citation.volume | 61 | - |
dc.citation.number | 20 | - |
dc.contributor.affiliatedAuthor | Seo, Seung-Yong | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | OXYGEN-INDUCED RETINOPATHY | - |
dc.subject.keywordPlus | 90 HSP90 INHIBITORS | - |
dc.subject.keywordPlus | FACTOR-I HIF-1 | - |
dc.subject.keywordPlus | RETINAL NEOVASCULARIZATION | - |
dc.subject.keywordPlus | COMBINATORIAL LIBRARIES | - |
dc.subject.keywordPlus | BIOLOGICAL EVALUATION | - |
dc.subject.keywordPlus | PRIVILEGED STRUCTURES | - |
dc.subject.keywordPlus | DEGUELIN DERIVATIVES | - |
dc.subject.keywordPlus | FACTOR PATHWAY | - |
dc.subject.keywordPlus | VEGF | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Medicinal | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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