| Autor: |
Tian-Shu Kang, Yong-Ming Yan, Yuan Tian, Jun Zhang, Minghui Zhang, Yuxin Shu, Jinbo Huang, Jing He, Cheng-Tian Tao, Qian Zhu, Jinke Gu, Xiaopeng Lu, Yong-Xian Cheng, Wei-Guo Zhu |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
iScience, Vol 27, Iss 6, Pp 110014- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2024.110014 |
| Popis: |
Summary: The NAD+-dependent deacetylase SIRT7 is a pivotal regulator of DNA damage response (DDR) and a promising drug target for developing cancer therapeutics. However, limited progress has been made in SIRT7 modulator discovery. Here, we applied peptide-based deacetylase platforms for SIRT7 enzymatic evaluation and successfully identified a potent SIRT7 inhibitor YZL-51N. We initially isolated bioactive YZL-51N from cockroach (Periplaneta americana) extracts and then developed the de novo synthesis of this compound. Further investigation revealed that YZL-51N impaired SIRT7 enzymatic activities through occupation of the NAD+ binding pocket. YZL-51N attenuated DNA damage repair induced by ionizing radiation (IR) in colorectal cancer cells and exhibited a synergistic anticancer effect when used in combination with etoposide. Overall, our study not only identified YZL-51N as a selective SIRT7 inhibitor from insect resources, but also confirmed its potential use in combined chemo-radiotherapy by interfering in the DNA damage repair process. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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