Nitric oxide synthase 2 (iNOS) (iNOS)

Nitric oxide synthase 2 (iNOS) is an inducible enzyme that catalyzes the synthesis of nitric oxide (NO) from L-arginine in response to inflammatory stimuli (UniProt: P35228). While constitutive isoforms of nitric oxide synthase provide low levels of NO for physiological signaling, iNOS is expressed at high levels following induction by cytokines such as Interleukin-1 beta (IL-1β) and Tumor Necrosis Factor-alpha (TNF-α) (PubMed: 7528661). The high-output NO produced by iNOS serves as a potent antimicrobial and antitumor agent within the innate immune system, but its overproduction is linked to the pathophysiology of chronic inflammatory diseases and septic shock (PubMed: 11441098). Consequently, iNOS is a major therapeutic target for conditions like rheumatoid arthritis, asthma, and inflammatory bowel disease. Pharmacological modulation involves either direct inhibition of the enzyme's catalytic site using small molecules like 1400W or the suppression of its expression through corticosteroids (PubChem: CID 445070). Clinical development of iNOS inhibitors has faced challenges regarding isoform selectivity and the potential for systemic side effects related to blood pressure regulation.

Other names

Inducible nitric oxide synthaseNOS2Nitric oxide synthase, inducibleNOS-IIHepatocyte NOS

Inhibition of the enzymatic activity of iNOS by competing with the substrate L-arginine or by preventing the transcriptional induction of the NOS2 gene through the inhibition of pro-inflammatory signaling pathways (PubMed: 11441098).