Reactive electrophilic and oxidative small molecules (REOS)

Reactive electrophilic and oxidative small molecules (REOS) encompass a diverse group of chemically active species, including reactive oxygen species (ROS), reactive nitrogen species (RNS), and lipid-derived electrophiles such as 4-hydroxynonenal [PMID: 28851707]. While these molecules play essential roles in physiological signaling pathways at low concentrations—regulating processes like vascular tone, oxygen sensing, and immune cell activation—their excessive accumulation leads to oxidative and electrophilic stress [PMID: 30268468]. This stress results in the damaging modification of critical cellular components, including DNA, proteins, and lipids, which is a hallmark of various pathologies such as cancer, neurodegeneration, and chronic inflammation [PMID: 24581455]. In a therapeutic context, REOS are generally viewed as pathological drivers or stressors rather than traditional drug targets like receptors or enzymes [PMID: 29117586]. Pharmacological interventions typically focus on scavenging these species directly using antioxidants or activating endogenous defense mechanisms, such as the Keap1-Nrf2-ARE pathway, to enhance cellular resilience and detoxification [PMID: 27003265]. Consequently, while they are central to disease biology, they represent a broad chemical class of stressors rather than a discrete, targetable biological entity.

Other names

Reactive oxygen speciesROSReactive nitrogen speciesRNSElectrophilic speciesOxidative stressorsElectrophilic stressors

Direct scavenging of reactive species, catalytic neutralization of oxidants, or induction of the antioxidant response element (ARE) through the modulation of the Keap1-Nrf2 pathway.