A ‘click’ chemistry approach to novel entinostat (MS-275) based class I histone deacetylase proteolysis targeting chimeras

Click 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 identifie...

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Autores principales: Cross, Jasmine M., Coulson, Megan E., Smalley, Joshua P., Pytel, Wiktoria A., Ismail, Ozair, Trory, Justin S., Cowley, Shaun M., Hodgkinson, James T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: RSC 2022
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9749924/
https://www.ncbi.nlm.nih.gov/pubmed/36545434
http://dx.doi.org/10.1039/d2md00199c
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author Cross, Jasmine M.
Coulson, Megan E.
Smalley, Joshua P.
Pytel, Wiktoria A.
Ismail, Ozair
Trory, Justin S.
Cowley, Shaun M.
Hodgkinson, James T.
author_facet Cross, Jasmine M.
Coulson, Megan E.
Smalley, Joshua P.
Pytel, Wiktoria A.
Ismail, Ozair
Trory, Justin S.
Cowley, Shaun M.
Hodgkinson, James T.
author_sort Cross, Jasmine M.
collection PubMed
description Click 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.
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spelling pubmed-97499242022-12-20 A ‘click’ chemistry approach to novel entinostat (MS-275) based class I histone deacetylase proteolysis targeting chimeras Cross, Jasmine M. Coulson, Megan E. Smalley, Joshua P. Pytel, Wiktoria A. Ismail, Ozair Trory, Justin S. Cowley, Shaun M. Hodgkinson, James T. RSC Med Chem Chemistry Click 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. RSC 2022-11-01 /pmc/articles/PMC9749924/ /pubmed/36545434 http://dx.doi.org/10.1039/d2md00199c Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Cross, Jasmine M.
Coulson, Megan E.
Smalley, Joshua P.
Pytel, Wiktoria A.
Ismail, Ozair
Trory, Justin S.
Cowley, Shaun M.
Hodgkinson, James T.
A ‘click’ chemistry approach to novel entinostat (MS-275) based class I histone deacetylase proteolysis targeting chimeras
title A ‘click’ chemistry approach to novel entinostat (MS-275) based class I histone deacetylase proteolysis targeting chimeras
title_full A ‘click’ chemistry approach to novel entinostat (MS-275) based class I histone deacetylase proteolysis targeting chimeras
title_fullStr A ‘click’ chemistry approach to novel entinostat (MS-275) based class I histone deacetylase proteolysis targeting chimeras
title_full_unstemmed A ‘click’ chemistry approach to novel entinostat (MS-275) based class I histone deacetylase proteolysis targeting chimeras
title_short A ‘click’ chemistry approach to novel entinostat (MS-275) based class I histone deacetylase proteolysis targeting chimeras
title_sort ‘click’ chemistry approach to novel entinostat (ms-275) based class i histone deacetylase proteolysis targeting chimeras
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9749924/
https://www.ncbi.nlm.nih.gov/pubmed/36545434
http://dx.doi.org/10.1039/d2md00199c
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