Related Experiment Video

Updated: Jan 19, 2026

Receptor Downregulation in MVBs
01:15

Receptor Downregulation in MVBs

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Nox1 downregulators: A new class of therapeutics

Matthias Barton1, Matthias R Meyer2, Eric R Prossnitz3

  • 1Molecular Internal Medicine, University of Zürich, Zürich, Switzerland; Andreas Grüntzig Foundation, Zürich, Switzerland.

Steroids
|September 14, 2019
PubMed

Insights

Small molecules targeting the G protein-coupled estrogen receptor (GPER) reduce Nox1 levels, offering potential treatments for cardiovascular, kidney, and other diseases linked to reactive oxygen species (ROS). These Nox1 downregulators (NDRs) show promise in preclinical studies.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Pathophysiology

Background:

  • Chronic non-communicable diseases share a common mechanism involving increased reactive oxygen species (ROS) production by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox).
  • Nox1, a specific Nox isoform, is implicated in cardiovascular disease, kidney disease, and cancer pathogenesis.
  • G protein-coupled estrogen receptor (GPER) regulates the expression and activity of Nox1.

Purpose of the Study:

  • To identify novel therapeutic agents targeting Nox1.
  • To explore the potential of GPER blockers as selective Nox1 downregulators (NDRs).

Main Methods:

  • Identification of orally active small-molecule GPER blockers.
  • Preclinical evaluation of NDRs in disease models.

Main Results:

  • NDRs were identified as selective Nox1 downregulators.
  • Preclinical studies demonstrated beneficial effects of NDRs in vascular disease, hypertension, and glomerular renal injury.

Conclusions:

  • NDRs that reduce Nox1 protein levels hold therapeutic potential for a range of non-communicable diseases.
  • Potential applications include cardiovascular conditions (hypertension, HFpEF), chronic renal disease, cerebrovascular disease, and cancer.
Keywords:
Chronic renal diseaseCoronary artery diseaseHFpEFHeart failureHypertensionNADPH oxidaseNon-communicable diseasesOxidative stressStrokeSuperoxideVascular

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