Nucleotide Analog ARL67156 as a Lead Structure for the Development of CD39 and Dual CD39/CD73 Ectonucleotidase Inhibitors.
ARL67156
CD39
CD73
docking
dual-target inhibitors
ecto-5’-nucleotidase
nucleoside triphosphate diphosphohydrolase1 (NTPDase1)
nucleotides
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2020
2020
Historique:
received:
07
06
2020
accepted:
04
08
2020
entrez:
5
10
2020
pubmed:
6
10
2020
medline:
6
10
2020
Statut:
epublish
Résumé
Nucleoside triphosphate diphosphohydrolase1 (NTPDase1, CD39) inhibitors have potential as novel drugs for the (immuno)therapy of cancer. They increase the extracellular concentration of immunostimulatory ATP and reduce the formation of AMP, which can be further hydrolyzed by ecto-5'-nucleotidase (CD73) to immunosuppressive, cancer-promoting adenosine. In the present study, we synthesized analogs and derivatives of the standard CD39 inhibitor ARL67156, a nucleotide analog which displays a competitive mechanism of inhibition. Structure-activity relationships were analyzed at the human enzyme with respect to substituents in the
Identifiants
pubmed: 33013365
doi: 10.3389/fphar.2020.01294
pmc: PMC7508162
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1294Informations de copyright
Copyright © 2020 Schäkel, Schmies, Idris, Luo, Lee, Lopez, Mirza, Vu, Pelletier, Sévigny, Namasivayam and Müller.
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