Nitric oxide synthase 2 (Inducible nitric oxide synthase) (NOS2 (iNOS))

Inducible nitric oxide synthase (iNOS), also known as Nitric oxide synthase 2 (NOS2), is a key enzyme that produces large amounts of nitric oxide (NO) from the amino acid L-arginine in response to inflammatory stimuli (UniProt P35228). Unlike the constitutive isoforms (nNOS and eNOS), iNOS is typically not present in healthy tissues but is rapidly expressed in macrophages and other cells following exposure to cytokines or bacterial endotoxins (PubMed: 17508917). The NO generated by iNOS plays a vital role in the immune system by acting as a cytotoxic agent against bacteria, parasites, and tumor cells (NCBI Gene: 4843). However, dysregulated or chronic overproduction of NO by iNOS is a major driver of tissue damage in inflammatory diseases such as rheumatoid arthritis, asthma, and inflammatory bowel disease (PubMed: 11544358). In the context of sepsis, excessive iNOS activity leads to systemic vasodilation and life-threatening hypotension (PubMed: 15128295). Pharmacological targeting of iNOS focuses on the development of selective small-molecule inhibitors that block the enzyme's active site or prevent its dimerization, aiming to reduce pathological NO levels without interfering with the essential physiological functions of other NOS isoforms. Clinical interest in iNOS inhibitors remains high for treating chronic inflammatory conditions and preventing the progression of certain cancers where NO promotes angiogenesis and tumor growth (PubMed: 21169518).

Other names

iNOSNOS2NOS-IIHEP-NOSNitric oxide synthase, induciblePeptidyl-L-arginine,NADPH:oxygen oxidoreductase

Competitive inhibition of the L-arginine binding site, inhibition of the heme-binding site, or prevention of enzyme dimerization (PubMed: 15128295).