Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A.
Journal
ACS omega
ISSN: 2470-1343
Titre abrégé: ACS Omega
Pays: United States
ID NLM: 101691658
Informations de publication
Date de publication:
09 Jun 2020
09 Jun 2020
Historique:
received:
03
03
2020
accepted:
13
05
2020
entrez:
18
6
2020
pubmed:
18
6
2020
medline:
18
6
2020
Statut:
epublish
Résumé
Lactate dehydrogenase A (LDHA) is frequently overexpressed in tumors, thereby sustaining high glycolysis rates, tumor growth, and chemoresistance. High-throughput screening resulted in the identification of phthalimide and dibenzofuran derivatives as novel lactate dehydrogenase inhibitors, selectively inhibiting the activity of the LDHA isoenzyme. Cocrystallization experiments confirmed target engagement in addition to demonstrating binding to a novel allosteric binding site present in all four LDHA subunits of the LDH5 homotetramer.
Identifiants
pubmed: 32548488
doi: 10.1021/acsomega.0c00715
pmc: PMC7288559
doi:
Types de publication
Journal Article
Langues
eng
Pagination
13034-13041Informations de copyright
Copyright © 2020 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare the following competing financial interest(s): All authors are current or former employees of Bayer AG. All authors were members of the respective research labs involved in the generation of these results.
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