Bioreducible Phosphonoamidate Pro-drug Inhibitor of Enolase : Proof of Concept Study
Copyright © 2020 American Chemical Society..
Glycolysis inhibition remains aspirational in cancer therapy. We recently described a promising phosphonate inhibitor of enolase for cancers harboring homozygous deletions of ENO1. Here, we describe the application of a nitroheterocycle phosphonoamidate pro-drug pair to capitalize on tumor hypoxia. This bioreducible prodrug exhibits greater-than 2-fold potency under hypoxic conditions compared to normoxia and exhibits robust stability in biological fluids. Our work provides strong in vitro proof-of-concept for using bioreduction as a pro-drug delivery strategy in the context of enolase inhibition.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2020 |
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Erschienen: |
2020 |
Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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Enthalten in: |
ACS medicinal chemistry letters - 11(2020), 7 vom: 09. Juli, Seite 1484-1489 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Yan, Victoria C [VerfasserIn] |
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Links: |
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Themen: |
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Anmerkungen: |
Date Revised 10.07.2021 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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doi: |
10.1021/acsmedchemlett.0c00203 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM312525265 |
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520 | |a Glycolysis inhibition remains aspirational in cancer therapy. We recently described a promising phosphonate inhibitor of enolase for cancers harboring homozygous deletions of ENO1. Here, we describe the application of a nitroheterocycle phosphonoamidate pro-drug pair to capitalize on tumor hypoxia. This bioreducible prodrug exhibits greater-than 2-fold potency under hypoxic conditions compared to normoxia and exhibits robust stability in biological fluids. Our work provides strong in vitro proof-of-concept for using bioreduction as a pro-drug delivery strategy in the context of enolase inhibition | ||
650 | 4 | |a Journal Article | |
700 | 1 | |a Yang, Kristine L |e verfasserin |4 aut | |
700 | 1 | |a Ballato, Elliot S |e verfasserin |4 aut | |
700 | 1 | |a Khadka, Sunada |e verfasserin |4 aut | |
700 | 1 | |a Shrestha, Prakriti |e verfasserin |4 aut | |
700 | 1 | |a Arthur, Kenisha |e verfasserin |4 aut | |
700 | 1 | |a Georgiou, Dimitra K |e verfasserin |4 aut | |
700 | 1 | |a Washington, Mykia |e verfasserin |4 aut | |
700 | 1 | |a Tran, Theresa |e verfasserin |4 aut | |
700 | 1 | |a Poral, Anton H |e verfasserin |4 aut | |
700 | 1 | |a Pham, Cong-Dat |e verfasserin |4 aut | |
700 | 1 | |a Yan, Matthew J |e verfasserin |4 aut | |
700 | 1 | |a Muller, Florian L |e verfasserin |4 aut | |
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