2020, A Decisive Decade for NADPH Oxidases Inhibitors

Area of Science:

• Biochemistry
• Pharmacology
• Enzymology

Background:

• NADPH oxidases (Noxs) are enzymes primarily generating reactive oxygen species (ROS).
• Nox enzymes present a dual pharmacological profile, requiring stimulation in some conditions and inhibition in others.
• Pathologies involving Noxs include vascular, cancerous, and neurological disorders.

Discussion:

• The complex role of Nox enzymes in pathophysiology complicates drug development.
• Existing Nox inhibitors have faced challenges in preclinical and clinical evaluations.
• Barriers to developing effective Nox inhibitors span both research and clinical stages.

Key Insights:

• Nox enzymes are the sole enzymes dedicated to ROS production, making them novel therapeutic targets.
• The dual nature of Nox activity (stimulation vs. inhibition) adds complexity to drug design.
• Significant obstacles impede the clinical translation of Nox-targeting drugs.

Outlook:

• Further research is needed to overcome preclinical and clinical hurdles for Nox inhibitors.
• Understanding Nox enzyme complexity is crucial for future therapeutic strategies.
• This review assesses current limitations in Nox inhibitor development.