Target intelligence / Profile preview

Endothelial nitric oxide synthase and Inducible nitric oxide synthase (eNOS/iNOS)

Target
eNOS/iNOS
Molecular classification
Enzyme, Oxidoreductase, Nitric oxide synthase
01

Overview

Nitric oxide synthases (NOS) are a family of enzymes that catalyze the production of nitric oxide (NO) from L-arginine (UniProt P29474, P35228). This entry encompasses two distinct isoforms: Endothelial nitric oxide synthase (eNOS or NOS3) and Inducible nitric oxide synthase (iNOS or NOS2). eNOS is primarily expressed in the vascular endothelium, where it produces NO to maintain vascular tone, inhibit platelet aggregation, and regulate blood pressure (StatPearls, Physiology, Nitric Oxide). iNOS is typically induced in response to inflammatory stimuli, such as cytokines or endotoxins, and produces significantly higher amounts of NO as a defense mechanism against pathogens (PubMed PMID 7531153). While eNOS activity is generally protective for the cardiovascular system, excessive iNOS activity is implicated in the pathogenesis of septic shock, chronic inflammation, and certain cancers (PubMed PMID 11544102). Pharmacological targeting of these enzymes involves inhibitors that compete with L-arginine or cofactors like tetrahydrobiopterin. Therapeutic development focuses on achieving isoform selectivity, particularly for iNOS, to treat inflammatory conditions without causing the hypertensive side effects associated with eNOS inhibition (PubMed PMID 9154002).

Other names
NOS3NOS2Nitric oxide synthase 3Nitric oxide synthase 2Endothelial NOSInducible NOSNOS IIINOS II
02

Mechanism of action

Competitive inhibition of the L-arginine binding site or interference with essential cofactors like tetrahydrobiopterin (BH4) to prevent the conversion of L-arginine to L-citrulline and nitric oxide (PubMed PMID 11544102).

03

Biological functions

VasodilationImmune responseSignal transductionInflammationPlatelet aggregation inhibition
04

Disease associations

Cardiovascular diseaseSepsisInflammationCancerNeurodegenerative diseaseRheumatoid arthritis
05

Safety considerations

Systemic hypertension (PubMed PMID 10653488)Impaired host defenseVasoconstrictionReduced regional blood flow
06

Interacting drugs

L-NMMA (Tilarginine)

6 more in the full profile.

07

Biomarkers

Serum nitrite/nitrate levels (PubMed PMID 15134532)Plasma L-citrullineCyclic guanosine monophosphate (cGMP) levelsExhaled nitric oxide (FeNO)

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