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Nitric oxide synthases (NOSs) are a family of enzymes that catalyze the production of nitric oxide (NO) from L-arginine in a reaction involving NADPH and oxygen as co-substrates, with several essential cofactors, such as FAD, FMN, and tetrahydrobiopterin (BH4)[1][7]. Three main NOS isoforms exist in mammals: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS)[2][3][7]. The inducible nitric oxide synthase (iNOS) isoform is distinguished by its ability to be strongly upregulated by inflammatory cytokines and microbial products in macrophages and many cell types, leading to high-output NO production as part of the host defense response[7][8]. iNOS acts independently of calcium for its activity, in contrast to the other two isoforms. Overproduction of NO by iNOS is implicated in various pathologies, including septic shock, chronic inflammation, and neurodegeneration[3][6]. iNOS is considered a promising but challenging therapeutic target, with several classes of selective inhibitors under preclinical or early clinical investigation, yet with notable safety and selectivity concerns due to the broad physiological roles of NO and similarities across NOS isoforms[6].
Inhibition of nitric oxide production (by competitive inhibition of iNOS enzyme active site); Downregulation of inflammatory responses due to suppressed NO synthesis
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