Non-covalent inhibitors of thioredoxin glutathione reductase with schistosomicidal activity in vivo.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 06 2023
22 06 2023
Historique:
received:
28
10
2022
accepted:
12
06
2023
medline:
26
6
2023
pubmed:
23
6
2023
entrez:
22
6
2023
Statut:
epublish
Résumé
Only praziquantel is available for treating schistosomiasis, a disease affecting more than 200 million people. Praziquantel-resistant worms have been selected for in the lab and low cure rates from mass drug administration programs suggest that resistance is evolving in the field. Thioredoxin glutathione reductase (TGR) is essential for schistosome survival and a validated drug target. TGR inhibitors identified to date are irreversible and/or covalent inhibitors with unacceptable off-target effects. In this work, we identify noncovalent TGR inhibitors with efficacy against schistosome infections in mice, meeting the criteria for lead progression indicated by WHO. Comparisons with previous in vivo studies with praziquantel suggests that these inhibitors outperform the drug of choice for schistosomiasis against juvenile worms.
Identifiants
pubmed: 37349300
doi: 10.1038/s41467-023-39444-y
pii: 10.1038/s41467-023-39444-y
pmc: PMC10287695
doi:
Substances chimiques
Schistosomicides
0
thioredoxin glutathione reductase
EC 1.6.4.-
Praziquantel
6490C9U457
NADH, NADPH Oxidoreductases
EC 1.6.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3737Subventions
Organisme : NIAID NIH HHS
ID : R33 AI127635
Pays : United States
Informations de copyright
© 2023. The Author(s).
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