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

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:11

Enthalten in:

ACS medicinal chemistry letters - 11(2020), 7 vom: 09. Juli, Seite 1484-1489

Sprache:

Englisch

Beteiligte Personen:

Yan, Victoria C [VerfasserIn]
Yang, Kristine L [VerfasserIn]
Ballato, Elliot S [VerfasserIn]
Khadka, Sunada [VerfasserIn]
Shrestha, Prakriti [VerfasserIn]
Arthur, Kenisha [VerfasserIn]
Georgiou, Dimitra K [VerfasserIn]
Washington, Mykia [VerfasserIn]
Tran, Theresa [VerfasserIn]
Poral, Anton H [VerfasserIn]
Pham, Cong-Dat [VerfasserIn]
Yan, Matthew J [VerfasserIn]
Muller, Florian L [VerfasserIn]

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Anmerkungen:

Date Revised 10.07.2021

published: Electronic-eCollection

Citation Status PubMed-not-MEDLINE

doi:

10.1021/acsmedchemlett.0c00203

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM312525265