Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase)

Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase, commonly called NOX) is a family of membrane-bound enzyme complexes whose primary function is the controlled production of reactive oxygen species (ROS) through the reduction of oxygen using electrons from NADPH. The classical phagocyte enzyme (NOX2) consists of several membrane and cytosolic subunits that assemble to enable a respiratory burst essential for microbial killing in innate immunity. NOX enzymes exist in several isoforms (NOX1–NOX5, DUOX1, DUOX2) with tissue-specific expression and roles in signal transduction, cell proliferation, angiogenesis, and host defense. While NOX-derived ROS are vital for physiological processes, dysregulation or overactivity is linked to numerous pathologies, including inflammation, neurodegeneration, cardiovascular disease, cancer, and chemoresistance in leukemia. Several small-molecule and peptide inhibitors are in preclinical and clinical development, but concerns remain over selectivity, safety, and on-target versus off-target effects. Biomarkers such as NOX2 expression and ROS levels, as well as regulators of NADPH supply like NAMPT, are under investigation for patient selection and monitoring.

Other names

NOXNOX1 (for isoform 1)NOX2 (for isoform 2, also known as gp91phox)NOX3, NOX4, NOX5Dual oxidases (DUOX1, DUOX2)Phagocyte oxidase (for NOX2 especially)gp91phox (catalytic core of NOX2)

Inhibition of ROS production by blocking the catalytic activity or assembly of the NADPH oxidase complex. Inhibition of the electron transfer from NADPH to molecular oxygen, preventing superoxide anion and hydrogen peroxide formation. Modulation of phagocyte respiratory burst and immune effector functions. Indirectly modulating downstream oxidative stress signaling.