Nitric oxide synthase, inducible (iNOS) (iNOS)

Inducible nitric oxide synthase (iNOS), also known as NOS2, is a high-capacity enzyme that produces nitric oxide (NO) from L-arginine in response to inflammatory stimuli such as cytokines and bacterial lipopolysaccharides [5, 15]. Unlike the constitutive isoforms (nNOS and eNOS), iNOS is calcium-independent and can generate sustained, high levels of NO for hours or days [1, 12]. This high-output NO is a critical component of the innate immune system, acting as a potent antimicrobial and antitumoral agent through the formation of reactive nitrogen species [8, 18]. However, chronic or excessive iNOS activation is implicated in the pathogenesis of various inflammatory and autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease, and asthma, as well as neurodegenerative conditions like Alzheimer's and Parkinson's diseases [9, 11, 13]. In clinical settings, iNOS is a major therapeutic target for conditions characterized by pathological NO overproduction, such as septic shock, though achieving high isoform selectivity remains a significant challenge to avoid interfering with the essential physiological roles of eNOS and nNOS [5, 17]. Current drug development efforts focus on selective iNOS inhibitors, such as GW274150 and 1400W, which aim to reduce nitrosative stress without causing the systemic hypotension associated with non-selective NOS inhibition [5, 9].

Other names

NOS2NOS type IIInducible NO synthaseHepatocyte NOSHEP-NOSPeptidyl-cysteine S-nitrosylase NOS2NOS2A

Competitive inhibition of the L-arginine binding site within the oxygenase domain, preventing the conversion of L-arginine to nitric oxide and L-citrulline.