YZL-51N functions as a selective inhibitor of SIRT7 by NAD+ competition to impede DNA damage repair.
iScience
; 27(6): 110014, 2024 Jun 21.
Article
em En
| MEDLINE
| ID: mdl-38947512
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Idioma:
En
Revista:
IScience
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China