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YZL-51N functions as a selective inhibitor of SIRT7 by NAD+ competition to impede DNA damage repair
- Source :
- iScience, Vol 27, Iss 6, Pp 110014- (2024)
- Publication Year :
- 2024
- Publisher :
- Elsevier, 2024.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 25890042
- Volume :
- 27
- Issue :
- 6
- Database :
- Directory of Open Access Journals
- Journal :
- iScience
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.713a4c4ce50a4b0a81c7306164ca42ef
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.isci.2024.110014