Target intelligence / Profile preview

Nitric oxide synthase 2 and Cyclooxygenase-2 (iNOS/COX-2)

Target
iNOS/COX-2
Molecular classification
Enzyme, Oxidoreductase, Oxygenase
01

Overview

Inducible nitric oxide and prostaglandin E2 production refers to a coordinated biological process involving the synthesis of two major inflammatory mediators: nitric oxide (NO) and prostaglandin E2 (PGE2). This production is primarily driven by the inducible enzymes nitric oxide synthase 2 (iNOS or NOS2) and cyclooxygenase-2 (COX-2 or PTGS2), which are typically expressed at low levels but are rapidly upregulated in response to pro-inflammatory stimuli like lipopolysaccharides (LPS) or cytokines (UniProt P35228, P35354). Nitric oxide serves as a potent vasodilator and signaling molecule, but its overproduction can lead to oxidative stress and tissue damage, while PGE2 is a key lipid mediator responsible for pain sensitization, fever, and increased vascular permeability (PubMed: 10454021). In drug discovery, the inhibition of this dual production is a standard phenotypic readout for evaluating the efficacy of anti-inflammatory compounds. Therapeutic strategies often involve non-steroidal anti-inflammatory drugs (NSAIDs) that target COX-2 or selective inhibitors of iNOS to manage conditions such as rheumatoid arthritis, osteoarthritis, and chronic inflammatory diseases (PubMed: 15630134). Because this term describes a downstream physiological outcome of multiple enzymatic pathways rather than a single molecular entity, it is classified as a biological process or assay readout rather than a discrete therapeutic target.

Other names
Inducible nitric oxide and prostaglandin E2 productioniNOS/COX-2 pathwayInflammatory mediator productionNOS2/PTGS2
02

Mechanism of action

Inhibition of the enzymatic activity or transcriptional expression of Nitric Oxide Synthase 2 (iNOS) and Cyclooxygenase-2 (COX-2) to reduce the synthesis of nitric oxide and prostaglandin E2.

03

Biological functions

Immune responseInflammationVasodilationPain signalingThermoregulation
04

Disease associations

InflammationCancerRheumatoid arthritisOsteoarthritisSepsisNeurodegenerative disease
05

Safety considerations

Cardiovascular toxicityGastrointestinal irritationRenal impairmentHypotensionImpaired wound healing
06

Interacting drugs

Celecoxib

6 more in the full profile.

07

Biomarkers

Nitrite levelsNitrate levelsProstaglandin E2 (PGE2) concentrationiNOS protein expressionCOX-2 mRNA levels

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