A 'click' chemistry approach to novel entinostat (MS-275) based class I histone deacetylase proteolysis targeting chimeras
journal contribution
posted on 2023-06-23, 15:38 authored by Jasmine M Cross, Megan E Coulson, Joshua P Smalley, Wiktoria A Pytel, Ozair Ismail, Justin S Trory, Shaun M Cowley, James T HodgkinsonClick chemistry was utilised to prepare a library of PROTACs based on entinostat a class I histone deacetylase (HDAC) inhibitor in clinical trials. A novel PROTAC JMC-137 was identified as a HDAC1/2 and HDAC3 degrader in HCT116 cells. However, potency was compromised compared to previously identified class I HDAC PROTACs highlighting the importance in the choice of HDAC ligand, functional group for linker attachment and positioning in PROTAC design.
Funding
This work was supported by the EPSRC (EP/S030492/1) in the laboratory of J. T. H. The laboratory of S. M. C. was supported by a senior nonclinical fellowship from the MRC (MR/J009202/1) and BBSRC project grants (BB/N002954/1, BB/P021689/1).
History
Citation
Jasmine, M. (2022). A ‘click’chemistry approach to novel entinostat (MS-275) based class I histone deacetylase proteolysis targeting chimeras. RSC Medicinal Chemistry, 13(12), 1634-1639.Author affiliation
Leicester Institute of Structural and Chemical Biology, School of ChemistryVersion
- VoR (Version of Record)
Published in
RSC MEDICINAL CHEMISTRYVolume
13Issue
12Pagination
634-1639Publisher
ROYAL SOC CHEMISTRYeissn
2632-8682Acceptance date
2022-09-05Copyright date
2022Available date
2023-06-23Publisher DOI
Language
EnglishPublisher version
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