Targeted Protein Degradation by Chimeric Compounds using Hydrophobic E3 Ligands and Adamantane Moiety.
adamantane
chimeric compound
hydrophobic tagging
protein degradation
Journal
Pharmaceuticals (Basel, Switzerland)
ISSN: 1424-8247
Titre abrégé: Pharmaceuticals (Basel)
Pays: Switzerland
ID NLM: 101238453
Informations de publication
Date de publication:
25 Feb 2020
25 Feb 2020
Historique:
received:
20
01
2020
revised:
19
02
2020
accepted:
19
02
2020
entrez:
29
2
2020
pubmed:
29
2
2020
medline:
29
2
2020
Statut:
epublish
Résumé
Targeted protein degradation using small chimeric molecules, such as proteolysis-targeting chimeras (PROTACs) and specific and nongenetic inhibitors of apoptosis protein [IAP]-dependent protein erasers (SNIPERs), is a promising technology in drug discovery. We recently developed a novel class of chimeric compounds that recruit the aryl hydrocarbon receptor (AhR) E3 ligase complex and induce the AhR-dependent degradation of target proteins. However, these chimeras contain a hydrophobic AhR E3 ligand, and thus, degrade target proteins even in cells that do not express AhR. In this study, we synthesized new compounds in which the AhR ligands were replaced with a hydrophobic adamantane moiety to investigate the mechanisms of AhR-independent degradation. Our results showed that the compounds,
Identifiants
pubmed: 32106507
pii: ph13030034
doi: 10.3390/ph13030034
pmc: PMC7151680
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Japan Society for the Promotion of Science
ID : JP19K07009
Déclaration de conflit d'intérêts
M.N. received a research fund from Daiichi Sankyo Pharmaceutical Co., Ltd. All other authors declare no conflict of interest.
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