YZL-51N functions as a selective inhibitor of SIRT7 by NAD+ competition to impede DNA damage repair.
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.
Pubmed ID: 38947512 RIS Download
Research resources used in this publication
Additional research tools detected in this publication
Antibodies used in this publication
- Horseradish enzyme labeled goat anti-rabbit IgG (H+L) (affinity purification) (RRID:AB_2747412)
- Horseradish enzyme labeled goat anti-mouse IgG (H+L) (affinity purification) (RRID:AB_2747415)
- 6*His, His-Tag antibody (RRID:AB_2857904)
- Anti-PAR Polymer Monoclonal Antibody (RRID:AB_2572318)
- Anti-Succinyllysine Mouse mAb (RRID:AB_2942099)
- Pan anti-crotonyllysine antibody (clone 4D5) (RRID:AB_2877695)
- Pan anti-butyryllysine antibody (RRID:AB_2687946)
- Acetylated-Lysine Antibody (RRID:AB_331805)
- α Tubulin antibody (A-6) (RRID:AB_2832217)
- ATM (phospho S1981) antibody [EP1890Y] (RRID:AB_1640207)
- ATM antibody [Y170] (RRID:AB_725574)
- Succinyl-Histone H3 (Lys122) rabbit pAb (RRID:AB_2868522)
- Histone-H3 antibody (RRID:AB_2716755)
- Histone H3 (acetyl K18) antibody - ChIP Grade (RRID:AB_298692)
- H3K14ac-human (RRID:AB_880442)
- Histone H3 (acetyl K9) antibody - ChIP Grade (RRID:AB_2118292)
- SIRT1 (B-7) (RRID:AB_1129462)
- Rabbit monoclonal anti-SirT6 (D8D12) (RRID:AB_2636969)
- SIRT7 (H-105) (RRID:AB_10611782)
Associated grants
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This is a list of tools and resources that we have found mentioned in this publication.
BALB/cAnN-Foxn1nu/nu/Rj (tool)
RRID:IMSR_RJ:BALB-C-NUDE
Mus musculus with name BALB/cAnN-Foxn1nu/nu/Rj from IMSR.
View all literature mentionsHorseradish enzyme labeled goat anti-rabbit IgG (H+L) (affinity purification) (antibody)
RRID:AB_2747412
This polyclonal secondary targets IgG (H+L)
View all literature mentionsHorseradish enzyme labeled goat anti-mouse IgG (H+L) (affinity purification) (antibody)
RRID:AB_2747415
This polyclonal secondary targets IgG (H+L)
View all literature mentions6*His, His-Tag antibody (antibody)
RRID:AB_2857904
This monoclonal targets 6*His, His-Tag
View all literature mentionsAnti-PAR Polymer Monoclonal Antibody (antibody)
RRID:AB_2572318
This monoclonal targets PAR
View all literature mentionsAnti-Succinyllysine Mouse mAb (antibody)
RRID:AB_2942099
This monoclonal targets Succinyllysine
View all literature mentionsPan anti-crotonyllysine antibody (clone 4D5) (antibody)
RRID:AB_2877695
This monoclonal targets lysine crotonylation
View all literature mentionsPan anti-butyryllysine antibody (antibody)
RRID:AB_2687946
This polyclonal targets butyryllysine
View all literature mentionsAcetylated-Lysine Antibody (antibody)
RRID:AB_331805
This polyclonal targets Acetylated-Lysine
View all literature mentionsα Tubulin antibody (A-6) (antibody)
RRID:AB_2832217
This monoclonal targets α Tubulin
View all literature mentionsATM (phospho S1981) antibody [EP1890Y] (antibody)
RRID:AB_1640207
This monoclonal targets ATM, phospho (Ser1981)
View all literature mentionsATM antibody [Y170] (antibody)
RRID:AB_725574
This monoclonal targets ATM antibody [Y170]
View all literature mentionsSuccinyl-Histone H3 (Lys122) rabbit pAb (antibody)
RRID:AB_2868522
This polyclonal targets H3K122su
View all literature mentionsHistone-H3 antibody (antibody)
RRID:AB_2716755
This polyclonal targets Histone-H3
View all literature mentionsHistone H3 (acetyl K18) antibody - ChIP Grade (antibody)
RRID:AB_298692
This polyclonal targets Histone H3 (acetyl K18) antibody - ChIP Grade
View all literature mentionsH3K14ac-human (antibody)
RRID:AB_880442
This monoclonal targets H3K14ac
View all literature mentionsHistone H3 (acetyl K9) antibody - ChIP Grade (antibody)
RRID:AB_2118292
This polyclonal targets HIST1H3A
View all literature mentionsSIRT1 (B-7) (antibody)
RRID:AB_1129462
This monoclonal targets SIRT1 (B-7)
View all literature mentionsRabbit monoclonal anti-SirT6 (D8D12) (antibody)
RRID:AB_2636969
This monoclonal targets SirT6
View all literature mentionsSIRT7 (H-105) (antibody)
RRID:AB_10611782
This monoclonal targets SIRT7 (H-105)
View all literature mentionsAddgene (data or information resource)
RRID:SCR_002037
Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentions
