Nitric oxide synthase 2 (inducible) (iNOS) (iNOS)

Inducible nitric oxide synthase (iNOS), also known as NOS2, is a calcium-independent enzyme that catalyzes the synthesis of nitric oxide (NO) from L-arginine in response to inflammatory stimuli (UniProt P35228). While constitutive isoforms (eNOS and nNOS) produce low levels of NO for signaling, iNOS is expressed primarily in macrophages and other immune cells following induction by cytokines or endotoxins, leading to sustained, high-level NO production. This high-output NO is essential for the host's innate immune defense against bacteria, parasites, and tumors due to its cytotoxic properties (PMID: 7503502). However, excessive or chronic iNOS activity is a major driver of pathological inflammation and is associated with conditions such as septic shock, rheumatoid arthritis, and neurodegenerative diseases (PMID: 17508917). In the context of oncology, iNOS-derived NO can promote tumor angiogenesis and immunosuppression, making it a target for both anti-inflammatory and anti-cancer therapies. Drug development has focused on selective iNOS inhibitors to avoid the cardiovascular side effects associated with inhibiting the constitutive eNOS isoform (PMID: 24630125).

Other names

NOS2NOS-IIInducible NOSHepatocyte NOSHEP-NOS

iNOS inhibitors typically act as competitive inhibitors at the L-arginine binding site or interact with the heme group or the cofactor tetrahydrobiopterin (BH4) to prevent the conversion of L-arginine to L-citrulline and nitric oxide (PMID: 17508917).