Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A

[Image: see text] 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 inh...

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Autores principales: Friberg, Anders, Rehwinkel, Hartmut, Nguyen, Duy, Pütter, Vera, Quanz, Maria, Weiske, Jörg, Eberspächer, Uwe, Heisler, Iring, Langer, Gernot
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288559/
https://www.ncbi.nlm.nih.gov/pubmed/32548488
http://dx.doi.org/10.1021/acsomega.0c00715
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author Friberg, Anders
Rehwinkel, Hartmut
Nguyen, Duy
Pütter, Vera
Quanz, Maria
Weiske, Jörg
Eberspächer, Uwe
Heisler, Iring
Langer, Gernot
author_facet Friberg, Anders
Rehwinkel, Hartmut
Nguyen, Duy
Pütter, Vera
Quanz, Maria
Weiske, Jörg
Eberspächer, Uwe
Heisler, Iring
Langer, Gernot
author_sort Friberg, Anders
collection PubMed
description [Image: see text] 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.
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spelling pubmed-72885592020-06-15 Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A Friberg, Anders Rehwinkel, Hartmut Nguyen, Duy Pütter, Vera Quanz, Maria Weiske, Jörg Eberspächer, Uwe Heisler, Iring Langer, Gernot ACS Omega [Image: see text] 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. American Chemical Society 2020-05-27 /pmc/articles/PMC7288559/ /pubmed/32548488 http://dx.doi.org/10.1021/acsomega.0c00715 Text en Copyright © 2020 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Friberg, Anders
Rehwinkel, Hartmut
Nguyen, Duy
Pütter, Vera
Quanz, Maria
Weiske, Jörg
Eberspächer, Uwe
Heisler, Iring
Langer, Gernot
Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A
title Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A
title_full Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A
title_fullStr Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A
title_full_unstemmed Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A
title_short Structural Evidence for Isoform-Selective Allosteric Inhibition of Lactate Dehydrogenase A
title_sort structural evidence for isoform-selective allosteric inhibition of lactate dehydrogenase a
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288559/
https://www.ncbi.nlm.nih.gov/pubmed/32548488
http://dx.doi.org/10.1021/acsomega.0c00715
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