2020
DOI: 10.26434/chemrxiv.12370469.v1
|View full text |Cite
Preprint
|
Sign up to set email alerts
|

HaloTag-Targeted Sirtuin Rearranging Ligand (SirReal) for the Development of Proteolysis Targeting Chimeras (PROTACs) Against the Lysine Deacetylase Sirtuin 2 (Sirt2)

Abstract: We have discovered the sirtuin rearranging ligands (SirReals) as a novel class of highly potent and selective inhibitors of the NAD+-dependent lysine deacetylase sirtuin 2 (Sirt2). In previous studies, conjugation of a SirReal with a ligand for the E3 ubiquitin ligase cereblon to form a so-called proteolysis targeting chimera (PROTAC), enabled small molecule-induced degradation of Sirt2. Here, we report the structure-based development of a chloroalkylated SirReal that induces the degradation of Sirt2 mediated … Show more

Help me understand this report
View published versions

Search citation statements

Order By: Relevance

Paper Sections

Select...
1

Citation Types

0
1
0

Year Published

2022
2022
2022
2022

Publication Types

Select...
1

Relationship

0
1

Authors

Journals

citations
Cited by 1 publication
(1 citation statement)
references
References 0 publications
0
1
0
Order By: Relevance
“…Compared to those traditional inhibitors, PROTACs may have several advantages for treating PD. For Very recently, some PROTACs with high selectivity and lower cytotoxicity have been developed for degrading HDAC6 or SIRT2 [137][138][139][140][141][142][143][144][145][146]. However, none of them have been tested in therapeutic potential for treating PD yet.…”
Section: Further Perspectivesmentioning
confidence: 99%
“…Compared to those traditional inhibitors, PROTACs may have several advantages for treating PD. For Very recently, some PROTACs with high selectivity and lower cytotoxicity have been developed for degrading HDAC6 or SIRT2 [137][138][139][140][141][142][143][144][145][146]. However, none of them have been tested in therapeutic potential for treating PD yet.…”
Section: Further Perspectivesmentioning
confidence: 99%