Inducible nitric oxide synthase (NOS2) (iNOS)

Inducible nitric oxide synthase (iNOS or NOS2) is a calcium-independent enzyme responsible for the high-output production of nitric oxide (NO) from L-arginine in response to inflammatory stimuli such as cytokines and bacterial lipopolysaccharides [1][2]. Unlike the constitutive isoforms (eNOS and nNOS), iNOS is typically not expressed in resting cells but is rapidly upregulated during immune activation to facilitate antimicrobial and antitumor activities [2]. However, the sustained overproduction of NO by iNOS is a major driver of chronic inflammation and oxidative stress, contributing to the pathogenesis of conditions like septic shock, asthma, and autoimmune disorders [3][4]. In drug discovery, iNOS is a significant therapeutic target where selective inhibitors are sought to reduce pathological NO levels without disrupting the essential physiological functions of other NOS isoforms [3]. Despite its potential, achieving high selectivity and managing the risk of immunosuppression remain primary challenges for clinical development [1].

Other names

Nitric oxide synthase 2NOS-IIHepatocyte NOSHEP-NOSiNOS pathway

Competitive inhibition of the L-arginine binding site or interference with enzyme dimerization to prevent the conversion of L-arginine to L-citrulline and nitric oxide [3].