The HDAC/HSP90 Inhibitor G570 Attenuated Blue Light-Induced Cell Migration in RPE Cells and Neovascularization in Mice through Decreased VEGF Production
Age-related macular degeneration (AMD) occurs due to an abnormality of retinal pigment epithelium (RPE) cells that leads to gradual degeneration of the macula. Currently, AMD drug pipelines are endowed with limited options, and anti-VEGF agents stand as the dominantly employed therapy. Despite the p...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Online Access: | https://www.mdpi.com/1420-3049/26/14/4359 |
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| author | Tai-Ju Hsu Kunal Nepali Chi-Hao Tsai Zuha Imtiyaz Fan-Li Lin George Hsiao Mei-Jung Lai Yu-Wen Cheng |
| author_facet | Tai-Ju Hsu Kunal Nepali Chi-Hao Tsai Zuha Imtiyaz Fan-Li Lin George Hsiao Mei-Jung Lai Yu-Wen Cheng |
| author_sort | Tai-Ju Hsu |
| collection | DOAJ |
| description | Age-related macular degeneration (AMD) occurs due to an abnormality of retinal pigment epithelium (RPE) cells that leads to gradual degeneration of the macula. Currently, AMD drug pipelines are endowed with limited options, and anti-VEGF agents stand as the dominantly employed therapy. Despite the proven efficacy of such agents, the evidenced side effects associated with their use underscore the need to elucidate other mechanisms involved and identify additional molecular targets for the sake of therapy improvement. The previous literature provided us with a solid rationale to preliminarily explore the potential of selective HDAC6 and HSP90 inhibitors to treat wet AMD. Rather than furnishing single-target agents (either HDAC6 or HSP90 inhibitor), this study recruited scaffolds endowed with the ability to concomitantly modulate both targets (HDAC6 and HSP90) for exploration. This plan was anticipated to accomplish the important goal of extracting amplified benefits via dual inhibition (HDAC6/HSP90) in wet AMD. As a result, G570 (indoline-based hydroxamate), a dual selective HDAC6-HSP90 inhibitor exerting its effects at micromolar concentrations, was pinpointed in the present endeavor to attenuate blue light-induced cell migration and retinal neovascularization by inhibiting VEGF production. In addition to the identification of a potential chemical tool (G570), the outcome of this study validates the candidate HDAC6-HSP90 as a compelling target for the development of futuristic therapeutics for wet AMD. |
| first_indexed | 2024-03-10T09:30:43Z |
| format | Article |
| id | doaj.art-9fabd4ff14134aeeb3099593b9b40ea7 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T09:30:43Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-9fabd4ff14134aeeb3099593b9b40ea72023-11-22T04:32:40ZengMDPI AGMolecules1420-30492021-07-012614435910.3390/molecules26144359The HDAC/HSP90 Inhibitor G570 Attenuated Blue Light-Induced Cell Migration in RPE Cells and Neovascularization in Mice through Decreased VEGF ProductionTai-Ju Hsu0Kunal Nepali1Chi-Hao Tsai2Zuha Imtiyaz3Fan-Li Lin4George Hsiao5Mei-Jung Lai6Yu-Wen Cheng7School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 100301, TaiwanSchool of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 100301, TaiwanSchool of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 100301, TaiwanSchool of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 100301, TaiwanDepartment of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 100301, TaiwanDepartment of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 100301, TaiwanPh.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei 100301, TaiwanSchool of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 100301, TaiwanAge-related macular degeneration (AMD) occurs due to an abnormality of retinal pigment epithelium (RPE) cells that leads to gradual degeneration of the macula. Currently, AMD drug pipelines are endowed with limited options, and anti-VEGF agents stand as the dominantly employed therapy. Despite the proven efficacy of such agents, the evidenced side effects associated with their use underscore the need to elucidate other mechanisms involved and identify additional molecular targets for the sake of therapy improvement. The previous literature provided us with a solid rationale to preliminarily explore the potential of selective HDAC6 and HSP90 inhibitors to treat wet AMD. Rather than furnishing single-target agents (either HDAC6 or HSP90 inhibitor), this study recruited scaffolds endowed with the ability to concomitantly modulate both targets (HDAC6 and HSP90) for exploration. This plan was anticipated to accomplish the important goal of extracting amplified benefits via dual inhibition (HDAC6/HSP90) in wet AMD. As a result, G570 (indoline-based hydroxamate), a dual selective HDAC6-HSP90 inhibitor exerting its effects at micromolar concentrations, was pinpointed in the present endeavor to attenuate blue light-induced cell migration and retinal neovascularization by inhibiting VEGF production. In addition to the identification of a potential chemical tool (G570), the outcome of this study validates the candidate HDAC6-HSP90 as a compelling target for the development of futuristic therapeutics for wet AMD.https://www.mdpi.com/1420-3049/26/14/4359HDAC inhibitorHSP90blue lightneovascularizationpharmacophorescaffold |
| spellingShingle | Tai-Ju Hsu Kunal Nepali Chi-Hao Tsai Zuha Imtiyaz Fan-Li Lin George Hsiao Mei-Jung Lai Yu-Wen Cheng The HDAC/HSP90 Inhibitor G570 Attenuated Blue Light-Induced Cell Migration in RPE Cells and Neovascularization in Mice through Decreased VEGF Production Molecules HDAC inhibitor HSP90 blue light neovascularization pharmacophore scaffold |
| title | The HDAC/HSP90 Inhibitor G570 Attenuated Blue Light-Induced Cell Migration in RPE Cells and Neovascularization in Mice through Decreased VEGF Production |
| title_full | The HDAC/HSP90 Inhibitor G570 Attenuated Blue Light-Induced Cell Migration in RPE Cells and Neovascularization in Mice through Decreased VEGF Production |
| title_fullStr | The HDAC/HSP90 Inhibitor G570 Attenuated Blue Light-Induced Cell Migration in RPE Cells and Neovascularization in Mice through Decreased VEGF Production |
| title_full_unstemmed | The HDAC/HSP90 Inhibitor G570 Attenuated Blue Light-Induced Cell Migration in RPE Cells and Neovascularization in Mice through Decreased VEGF Production |
| title_short | The HDAC/HSP90 Inhibitor G570 Attenuated Blue Light-Induced Cell Migration in RPE Cells and Neovascularization in Mice through Decreased VEGF Production |
| title_sort | hdac hsp90 inhibitor g570 attenuated blue light induced cell migration in rpe cells and neovascularization in mice through decreased vegf production |
| topic | HDAC inhibitor HSP90 blue light neovascularization pharmacophore scaffold |
| url | https://www.mdpi.com/1420-3049/26/14/4359 |
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