Small molecule compound ZYZ-384 targets SMYD3 to alleviate aging
Abstract SMYD3 is a chromatin modifier that facilitates the trimethylation of histone 3 lysine 4 (H3K4) to induce diverse biological activities. We have provided a brief demonstration of the anti-aging effect of ZYZ-384, a newly developed inhibitor targeting SMYD3. In order to validate the anti-sene...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-10345-y |
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| author | Yang Liu Dan Han Li Jin Xuena Xie Huibo Li Qian Ding Yizhun Zhu |
| author_facet | Yang Liu Dan Han Li Jin Xuena Xie Huibo Li Qian Ding Yizhun Zhu |
| author_sort | Yang Liu |
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| description | Abstract SMYD3 is a chromatin modifier that facilitates the trimethylation of histone 3 lysine 4 (H3K4) to induce diverse biological activities. We have provided a brief demonstration of the anti-aging effect of ZYZ-384, a newly developed inhibitor targeting SMYD3. In order to validate the anti-senescence effect of ZYZ-384, we utilized angiotensin II to induce senescence in two types of human endothelial cells (HMEC-1) and mouse endothelial cells (SVEC4-10), creating cellular models for senescence. Additionally, we employed D-galactose-induced subacute senescence animal models as well as natural senescence animal models. At the cellular level, we assessed proliferation capacity and intracellular markers associated with aging. Aging markers, SASP and differential metabolites were evaluated at an organismal level using animal models. Compared to senescent cells or animals, ZYZ-384 application significantly inhibited levels of aging markers in both senescent cell and senescent animal models while promoting cell proliferation. Furthermore, it suppressed expression of SMYD3 and H3K4me3 along with over expression of HSP 90 and NF-κB. Our study demonstrates that ZYZ-384 is an effective inhibitor targeting SMYD3 which can effectively delay aging. |
| format | Article |
| id | doaj-art-7b9e7752035644cfb658d55c0e2a089e |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-7b9e7752035644cfb658d55c0e2a089e2025-08-20T03:46:07ZengNature PortfolioScientific Reports2045-23222025-07-0115112110.1038/s41598-025-10345-ySmall molecule compound ZYZ-384 targets SMYD3 to alleviate agingYang Liu0Dan Han1Li Jin2Xuena Xie3Huibo Li4Qian Ding5Yizhun Zhu6State Key Laboratory of Quality Research in Chinese Medicine & Laboratory of Drug Discovery from Natural Resources and Industrialization, School of Pharmacy, Macau University of Science and TechnologyState Key Laboratory of Quality Research in Chinese Medicine & Laboratory of Drug Discovery from Natural Resources and Industrialization, School of Pharmacy, Macau University of Science and TechnologyState Key Laboratory of Quality Research in Chinese Medicine & Laboratory of Drug Discovery from Natural Resources and Industrialization, School of Pharmacy, Macau University of Science and TechnologyState Key Laboratory of Quality Research in Chinese Medicine & Laboratory of Drug Discovery from Natural Resources and Industrialization, School of Pharmacy, Macau University of Science and TechnologyState Key Laboratory of Quality Research in Chinese Medicine & Laboratory of Drug Discovery from Natural Resources and Industrialization, School of Pharmacy, Macau University of Science and TechnologyState Key Laboratory of Quality Research in Chinese Medicine & Laboratory of Drug Discovery from Natural Resources and Industrialization, School of Pharmacy, Macau University of Science and TechnologyState Key Laboratory of Quality Research in Chinese Medicine & Laboratory of Drug Discovery from Natural Resources and Industrialization, School of Pharmacy, Macau University of Science and TechnologyAbstract SMYD3 is a chromatin modifier that facilitates the trimethylation of histone 3 lysine 4 (H3K4) to induce diverse biological activities. We have provided a brief demonstration of the anti-aging effect of ZYZ-384, a newly developed inhibitor targeting SMYD3. In order to validate the anti-senescence effect of ZYZ-384, we utilized angiotensin II to induce senescence in two types of human endothelial cells (HMEC-1) and mouse endothelial cells (SVEC4-10), creating cellular models for senescence. Additionally, we employed D-galactose-induced subacute senescence animal models as well as natural senescence animal models. At the cellular level, we assessed proliferation capacity and intracellular markers associated with aging. Aging markers, SASP and differential metabolites were evaluated at an organismal level using animal models. Compared to senescent cells or animals, ZYZ-384 application significantly inhibited levels of aging markers in both senescent cell and senescent animal models while promoting cell proliferation. Furthermore, it suppressed expression of SMYD3 and H3K4me3 along with over expression of HSP 90 and NF-κB. Our study demonstrates that ZYZ-384 is an effective inhibitor targeting SMYD3 which can effectively delay aging.https://doi.org/10.1038/s41598-025-10345-yChromatin modifierSenescenceCell proliferationD-galactose |
| spellingShingle | Yang Liu Dan Han Li Jin Xuena Xie Huibo Li Qian Ding Yizhun Zhu Small molecule compound ZYZ-384 targets SMYD3 to alleviate aging Scientific Reports Chromatin modifier Senescence Cell proliferation D-galactose |
| title | Small molecule compound ZYZ-384 targets SMYD3 to alleviate aging |
| title_full | Small molecule compound ZYZ-384 targets SMYD3 to alleviate aging |
| title_fullStr | Small molecule compound ZYZ-384 targets SMYD3 to alleviate aging |
| title_full_unstemmed | Small molecule compound ZYZ-384 targets SMYD3 to alleviate aging |
| title_short | Small molecule compound ZYZ-384 targets SMYD3 to alleviate aging |
| title_sort | small molecule compound zyz 384 targets smyd3 to alleviate aging |
| topic | Chromatin modifier Senescence Cell proliferation D-galactose |
| url | https://doi.org/10.1038/s41598-025-10345-y |
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