Nitric oxide synthase 2 (inducible) (iNOS)

Nitric oxide synthase 2 (inducible), commonly referred to as iNOS, is a calcium-independent enzyme responsible for the high-output production of nitric oxide (NO) from the amino acid L-arginine (UniProt P35228). Unlike the constitutive isoforms (nNOS and eNOS), iNOS is typically not expressed in resting cells but is rapidly induced in macrophages and other cell types by pro-inflammatory stimuli such as cytokines and lipopolysaccharides (PMID: 15132156). The NO generated by iNOS serves as a critical component of the innate immune system, providing potent antimicrobial and antitumor activity through oxidative stress (PMID: 32353958). However, chronic or excessive iNOS activity is linked to the pathogenesis of various inflammatory conditions, including rheumatoid arthritis, asthma, and septic shock, where overproduction of NO leads to tissue damage and vasodilation (PubChem NOS2). Therapeutic strategies targeting iNOS involve small-molecule inhibitors designed to selectively block its catalytic activity without interfering with the homeostatic functions of other NOS isoforms (PMID: 32353958). While several selective inhibitors have reached clinical trials, challenges remain regarding achieving sufficient selectivity to avoid cardiovascular side effects like hypotension (PMID: 15132156).

Other names

NOS2Inducible nitric oxide synthaseNOS-IIHepatocyte NOSiNOS

Competitive inhibition of the L-arginine binding site or the heme-binding domain to prevent the conversion of L-arginine to nitric oxide and L-citrulline.