Target intelligence / Profile preview

Tumor-associated NADH oxidase (ENOX2) (ENOX2)

Target
ENOX2
Molecular classification
Enzyme, Oxidoreductase, Cell-surface protein, Growth-related NADH (hydroquinone) oxidase
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Overview

Tumor-associated NADH oxidase (ENOX2, often termed tNOX) is a growth-related, cell-surface NADH (hydroquinone) oxidase found on cancer cells and only minimally or not detectably on most normal cells, where it catalyzes oxidation of NADH to NAD⁺ at the plasma membrane and participates in time-keeping/growth-related redox cycles that support tumor cell proliferation and survival. It belongs to a small ENOX (ectoenzyme NADH oxidase) family distinct from the classical membrane NADPH oxidase (NOX) enzymes, is encoded by a gene localized to Xq25–26, and has been cloned and biochemically characterized as a tumor-associated oxidoreductase whose selective inhibition (for example by ME-143) represents a potential anticancer therapeutic strategy and a basis for tumor-specific drug targeting and biomarker development.

Other names
tumor-associated NADH oxidasetNOXENOX2growth-related NADH oxidasecancer-specific NADH oxidasetumor-specific inhibitor-sensitive NADH oxidase
02

Mechanism of action

For ME-143 and related agents: inhibition of tumor-associated NADH oxidase (ENOX2/tNOX) leading to disruption of plasma membrane NADH oxidase activity, interference with growth-related redox cycling, inhibition of Wnt/β-catenin and other survival pathways, and induction of cancer cell death or growth arrest. More generally: selective inhibition of tumor-specific ENOX2 activity on cancer cell surfaces, exploiting differential expression/activity compared with normal cells

03

Biological functions

Cell proliferationCell growth regulationCell cycle progressionApoptosis modulationRedox regulation at the plasma membraneNADH (hydroquinone) oxidationContribution to cancer cell signaling and survival
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Disease associations

Cancer (multiple solid tumors and some hematologic malignancies)Potential role in tumor progression and tumor cell survivalPossible role in cancer immunogenicity
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Safety considerations

Potential on-target/off-tumor effects if ENOX2 or related NOX family oxidases are expressed in some normal or proliferating tissuesGeneral class concerns for redox/enzyme inhibitors, including possible effects on normal redox homeostasis and cell growth (based on ENOX family and NOX biology, not yet fully defined clinically)
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Interacting drugs

ME-143 (NV-143)

1 more in the full profile.

07

Biomarkers

ENOX2/tNOX expression or activity on the tumor cell surfacetumor-associated markercancer biomarker for presence of malignant cellsbiomarker for monitoring response to ENOX2-targeted therapies

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